amitriptyline/perphenazine (Rx)

Anxiety or Agitation with Depression

Indicated for (1) moderate-to-severe anxiety and/or agitation and depressed mood, (2) depression in whom anxiety and/or agitation are severe, and (3) depression and anxiety associated with chronic physical disease

Initial: 25 mg/2 mg or 25 mg/4 mg PO TID/QID, OR 50 mg/4 mg PO BID

Maintenance: 2 mg/25 mg or 4 mg/25 mg PO BID/QID, OR 50 mg/4 mg PO BID

10 mg/ 2 mg and 10 mg/4 mg can be used to increase flexibility in adjusting maintenance dosage to the lowest amount consistent with relief of symptoms

Do not exceed daily dose of 200 mg/16 mg

Schizophrenia with Depression

Indicated for patients with schizophrenic who have associated depressive symptoms

Initial: 50 mg/8 mg (ie, 2 tablets of 25 mg/4 mg) PO BID/TID; if needed a fourth dose may be given at bedtime

Maintenance: 2 mg/25 mg or 4 mg/25 mg PO BID/QID, OR 50 mg/4 mg PO BID

10 mg/ 2 mg and 10 mg/4 mg can be used to increase flexibility in adjusting maintenance dosage to the lowest amount consistent with relief of symptoms

Do not exceed daily dose of 200 mg/16 mg

Dosing Considerations

Depending on the condition being treated, therapeutic response may not be observed for several days up to 2-3 weeks, or longer

After a satisfactory response is noted, dosage should be reduced to the smallest amount necessary to obtain relief from the symptoms

Not recommended

Avoid; strong anticholinergic and sedative effects; may cause orthostatic hypotension (Beers criteria)

Consider alternatives; if must use, initiate with lower initial dose such as 1 tablet (amitriptyline 10 mg/perphenazine 4 mg) three/four times daily

Contraindicated (22)

• amisulpride

  amisulpride, perphenazine. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Increases risk of neuroleptic malignant syndrome.

• disopyramide

  amitriptyline and disopyramide both increase QTc interval. Contraindicated.
  
  perphenazine and disopyramide both increase QTc interval. Contraindicated.

• dronedarone

  dronedarone will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  dronedarone will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• fezolinetant

  perphenazine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

• fezolinetant

  amitriptyline will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

• ibutilide

  perphenazine and ibutilide both increase QTc interval. Contraindicated.
  
  amitriptyline and ibutilide both increase QTc interval. Contraindicated.

• indapamide

  perphenazine and indapamide both increase QTc interval. Contraindicated.
  
  amitriptyline and indapamide both increase QTc interval. Contraindicated.

• iobenguane I 123

  amitriptyline decreases effects of iobenguane I 123 by pharmacodynamic antagonism. Contraindicated. If clinically appropriate, discontinue drugs that decrease uptake of NE for at least 5 half-lives; may cause false-negative imaging results.

• metrizamide

  perphenazine, metrizamide. Mechanism: unknown. Contraindicated. Risk of seizure. D/C phenothiazine 24h before admin. of metrizamide.

• isocarboxazid

  isocarboxazid and amitriptyline both increase serotonin levels. Contraindicated.

• pentamidine

  perphenazine and pentamidine both increase QTc interval. Contraindicated.
  
  amitriptyline and pentamidine both increase QTc interval. Contraindicated.

• phenelzine

  phenelzine and amitriptyline both increase serotonin levels. Contraindicated.

• pimozide

  perphenazine and pimozide both increase QTc interval. Contraindicated.

• pimozide

  amitriptyline and pimozide both increase QTc interval. Contraindicated.

• procainamide

  amitriptyline and procainamide both increase QTc interval. Contraindicated.
  
  perphenazine and procainamide both increase QTc interval. Contraindicated.

• procarbazine

  procarbazine and amitriptyline both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI use.

• quinidine

  perphenazine and quinidine both increase QTc interval. Contraindicated.

• quinidine

  quinidine and amitriptyline both increase QTc interval. Contraindicated.

• safinamide

  amitriptyline, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

• selegiline

  selegiline and amitriptyline both increase serotonin levels. Contraindicated. Concurrent use or use within 14 days of selegiline treatment is contraindicated

• sotalol

  perphenazine and sotalol both increase QTc interval. Contraindicated.
  
  amitriptyline and sotalol both increase QTc interval. Contraindicated.

• tranylcypromine

  tranylcypromine and amitriptyline both increase serotonin levels. Contraindicated.

Serious - Use Alternative (193)

• adagrasib

  adagrasib, amitriptyline. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Each drug prolongs the QTc interval, which may increased the risk of Torsade de pointes, other serious arryhthmias, and sudden death. If coadministration unavoidable, more frequent monitoring is recommended for such patients.
  
  adagrasib, perphenazine. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Each drug prolongs the QTc interval, which may increased the risk of Torsade de pointes, other serious arryhthmias, and sudden death. If coadministration unavoidable, more frequent monitoring is recommended for such patients.

• albuterol

  amitriptyline, albuterol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• aminolevulinic acid oral

  aminolevulinic acid oral, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid administering other phototoxic drugs with aminolevulinic acid oral for 24 hr during perioperative period.

• aminolevulinic acid topical

  perphenazine increases toxicity of aminolevulinic acid topical by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration of photosensitizing drugs may enhance the phototoxic reaction to photodynamic therapy with aminolevulinic acid.

• amiodarone

  amitriptyline and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.
  
  perphenazine and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.

• amisulpride

  perphenazine and amisulpride both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered.

• amoxapine

  amitriptyline and amoxapine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and amoxapine both increase serotonin levels. Avoid or Use Alternate Drug.

• amitriptyline

  perphenazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• amoxapine

  perphenazine and amoxapine both increase QTc interval. Avoid or Use Alternate Drug.

• apomorphine

  perphenazine decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.
  
  apomorphine and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.

• arformoterol

  amitriptyline, arformoterol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• aripiprazole

  aripiprazole and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.

• arsenic trioxide

  amitriptyline and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.
  
  perphenazine and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.

• artemether

  artemether and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• artemether/lumefantrine

  perphenazine and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

• artemether/lumefantrine

  amitriptyline and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

• benzhydrocodone/acetaminophen

  benzhydrocodone/acetaminophen, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).
  
  benzhydrocodone/acetaminophen and amitriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• benzphetamine

  amitriptyline, benzphetamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• bromocriptine

  perphenazine decreases effects of bromocriptine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

• buprenorphine

  buprenorphine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine buccal

  buprenorphine buccal and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine subdermal implant

  buprenorphine subdermal implant and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine subdermal implant and amitriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine transdermal

  buprenorphine transdermal and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine transdermal and amitriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine, long-acting injection

  buprenorphine, long-acting injection and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine, long-acting injection and amitriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buspirone

  amitriptyline and buspirone both increase serotonin levels. Avoid or Use Alternate Drug.

• cabergoline

  perphenazine decreases effects of cabergoline by pharmacodynamic antagonism. Contraindicated.

• calcium/magnesium/potassium/sodium oxybates

  perphenazine, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  amitriptyline, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• chlorpromazine

  chlorpromazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  chlorpromazine and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.

• citalopram

  citalopram and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Citalopram may increase TCA levels. Increased risk of serotonin syndrome or neuroleptic malignant syndrome. Potential risk for QT prolongation. ECG monitoring is recommended.
  
  citalopram and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• clarithromycin

  perphenazine and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug.

• clarithromycin

  clarithromycin will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  amitriptyline and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug.

• clomipramine

  perphenazine and clomipramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and clomipramine both increase serotonin levels. Avoid or Use Alternate Drug.
  
  amitriptyline and clomipramine both increase QTc interval. Avoid or Use Alternate Drug.

• clonidine

  amitriptyline decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• dacomitinib

  dacomitinib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

• cyclobenzaprine

  amitriptyline and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug.

• dacomitinib

  dacomitinib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

• dasatinib

  dasatinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• degarelix

  degarelix and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.

• desipramine

  perphenazine and desipramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and desipramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and desipramine both increase serotonin levels. Avoid or Use Alternate Drug.

• desvenlafaxine

  amitriptyline and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

• dofetilide

  perphenazine and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.

• dexfenfluramine

  amitriptyline, dexfenfluramine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• dexmethylphenidate

  amitriptyline, dexmethylphenidate. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• dextroamphetamine

  amitriptyline, dextroamphetamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• dextromethorphan

  amitriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• diethylpropion

  amitriptyline, diethylpropion. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• dobutamine

  amitriptyline, dobutamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• dofetilide

  amitriptyline and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.

• dolasetron

  dolasetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• dopamine

  perphenazine decreases effects of dopamine by pharmacodynamic antagonism. Contraindicated.
  
  amitriptyline, dopamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• dopexamine

  amitriptyline, dopexamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• dosulepin

  perphenazine and dosulepin both increase QTc interval. Avoid or Use Alternate Drug.

• dosulepin

  amitriptyline and dosulepin both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and dosulepin both increase serotonin levels. Avoid or Use Alternate Drug.

• doxepin

  amitriptyline and doxepin both increase serotonin levels. Avoid or Use Alternate Drug.
  
  perphenazine and doxepin both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and doxepin both increase QTc interval. Avoid or Use Alternate Drug.

• dronedarone

  dronedarone and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  perphenazine and dronedarone both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and dronedarone both increase QTc interval. Avoid or Use Alternate Drug.

• droperidol

  perphenazine and droperidol both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and droperidol both increase QTc interval. Avoid or Use Alternate Drug.

• duloxetine

  duloxetine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• epinephrine

  epinephrine and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.

• encorafenib

  encorafenib and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• ephedrine

  amitriptyline, ephedrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• epinephrine

  epinephrine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline, epinephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• epinephrine racemic

  epinephrine racemic and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.
  
  epinephrine racemic and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline, epinephrine racemic. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• erythromycin base

  amitriptyline and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.
  
  erythromycin base will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
  
  erythromycin base will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  perphenazine and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  erythromycin ethylsuccinate will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
  
  erythromycin ethylsuccinate will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  perphenazine and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  erythromycin lactobionate will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  erythromycin lactobionate will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
  
  perphenazine and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin stearate

  erythromycin stearate will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  erythromycin stearate will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
  
  perphenazine and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.

• escitalopram

  escitalopram and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.
  
  escitalopram increases toxicity of amitriptyline by QTc interval. Avoid or Use Alternate Drug.

• fentanyl

  fentanyl, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fenfluramine

  amitriptyline, fenfluramine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• fentanyl intranasal

  fentanyl intranasal, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl transdermal

  fentanyl transdermal, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl transmucosal

  fentanyl transmucosal, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fexinidazole

  fexinidazole and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.

• fluconazole

  amitriptyline and fluconazole both increase QTc interval. Avoid or Use Alternate Drug.
  
  perphenazine and fluconazole both increase QTc interval. Avoid or Use Alternate Drug.

• fluoxetine

  fluoxetine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug.
  
  perphenazine and fluoxetine both increase QTc interval. Avoid or Use Alternate Drug.
  
  fluoxetine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.
  
  perphenazine will increase the level or effect of fluoxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
  
  fluoxetine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• fluphenazine

  fluphenazine and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.
  
  fluphenazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• fluvoxamine

  fluvoxamine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• formoterol

  perphenazine and formoterol both increase QTc interval. Avoid or Use Alternate Drug.

• formoterol

  amitriptyline and formoterol both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline, formoterol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• fosamprenavir

  fosamprenavir increases levels of amitriptyline by decreasing metabolism. Avoid or Use Alternate Drug.

• givosiran

  givosiran will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
  
  givosiran will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.

• granisetron

  granisetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.
  
  granisetron and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• haloperidol

  perphenazine and haloperidol both increase QTc interval. Avoid or Use Alternate Drug.

• guanfacine

  amitriptyline decreases effects of guanfacine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• haloperidol

  amitriptyline and haloperidol both increase QTc interval. Avoid or Use Alternate Drug.

• hydrocodone

  hydrocodone, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

• hydroxychloroquine sulfate

  hydroxychloroquine sulfate and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  hydroxychloroquine sulfate and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.

• imipramine

  amitriptyline and imipramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  perphenazine and imipramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and imipramine both increase serotonin levels. Avoid or Use Alternate Drug.

• iobenguane I 131

  amitriptyline will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.

• isocarboxazid

  isocarboxazid, perphenazine. Other (see comment). Contraindicated. Comment: Concurrent use may prolong or intensify the hypotensive, anticholinergic, or sedative effects of isocarboxazid or perphenazine.

• isoproterenol

  amitriptyline, isoproterenol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• itraconazole

  perphenazine and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

• ivosidenib

  ivosidenib and perphenazine both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of QTc prolonging drugs with ivosidenib or replace with alternate therapies. If coadministration of a QTc prolonging drug is unavoidable, monitor for increased risk of QTc interval prolongation.
  
  ivosidenib and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of QTc prolonging drugs with ivosidenib or replace with alternate therapies. If coadministration of a QTc prolonging drug is unavoidable, monitor for increased risk of QTc interval prolongation.

• ketoconazole

  perphenazine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• lasmiditan

  lasmiditan increases effects of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• levodopa

  perphenazine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

• lefamulin

  lefamulin and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• levalbuterol

  amitriptyline, levalbuterol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• levodopa inhaled

  perphenazine decreases effects of levodopa inhaled by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Phenothiazine/1st generation antipsychotics inhibit dopamine D2 receptors in varying degrees.

• levoketoconazole

  perphenazine and levoketoconazole both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and levoketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• levomilnacipran

  levomilnacipran and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• lisuride

  perphenazine decreases effects of lisuride by pharmacodynamic antagonism. Contraindicated.

• linezolid

  linezolid and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.

• lisdexamfetamine

  amitriptyline, lisdexamfetamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• lofepramine

  amitriptyline and lofepramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and lofepramine both increase serotonin levels. Avoid or Use Alternate Drug.
  
  perphenazine and lofepramine both increase QTc interval. Avoid or Use Alternate Drug.

• lorcaserin

  amitriptyline and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.
  
  perphenazine and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.

• lumefantrine

  perphenazine and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

• macimorelin

  macimorelin and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug. Macimorelin causes an increase of ~11 msec in the corrected QT interval. Avoid coadministration with drugs that prolong QT interval, which could increase risk for developing torsade de pointes-type ventricular tachycardia. Allow sufficient washout time of drugs that are known to prolong the QT interval before administering macimorelin.
  
  macimorelin and perphenazine both increase QTc interval. Avoid or Use Alternate Drug. Macimorelin causes an increase of ~11 msec in the corrected QT interval. Avoid coadministration with drugs that prolong QT interval, which could increase risk for developing torsade de pointes-type ventricular tachycardia. Allow sufficient washout time of drugs that are known to prolong the QT interval before administering macimorelin.

• maprotiline

  amitriptyline and maprotiline both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and maprotiline both increase serotonin levels. Avoid or Use Alternate Drug.
  
  perphenazine and maprotiline both increase QTc interval. Avoid or Use Alternate Drug.

• mefloquine

  mefloquine increases toxicity of amitriptyline by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.

• methyl aminolevulinate

  perphenazine, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

• meperidine

  amitriptyline and meperidine both increase serotonin levels. Avoid or Use Alternate Drug.

• metaproterenol

  amitriptyline, metaproterenol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• methamphetamine

  amitriptyline, methamphetamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• methyldopa

  perphenazine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

• methylene blue

  methylene blue and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.

• methylenedioxymethamphetamine

  amitriptyline, methylenedioxymethamphetamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• metoclopramide intranasal

  perphenazine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.
  
  perphenazine increases toxicity of metoclopramide intranasal by pharmacodynamic synergism. Avoid or Use Alternate Drug. Potential for additive effects, including increased frequency and severity of tardive dyskinesia, other extrapyramidal symptoms, and neuroleptic malignant syndrome.
  
  amitriptyline, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

• midodrine

  amitriptyline, midodrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• mobocertinib

  mobocertinib and perphenazine both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.

• milnacipran

  milnacipran and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• mirtazapine

  mirtazapine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• mobocertinib

  mobocertinib will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently

• moxifloxacin

  perphenazine and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• nefazodone

  nefazodone and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• nilotinib

  perphenazine and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.

• netupitant/palonosetron

  netupitant/palonosetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• nilotinib

  amitriptyline and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.

• norepinephrine

  amitriptyline, norepinephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• nortriptyline

  perphenazine and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.
  
  amitriptyline and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• octreotide

  perphenazine and octreotide both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and octreotide both increase QTc interval. Avoid or Use Alternate Drug.

• octreotide (Antidote)

  amitriptyline and octreotide (Antidote) both increase QTc interval. Avoid or Use Alternate Drug.
  
  perphenazine and octreotide (Antidote) both increase QTc interval. Avoid or Use Alternate Drug.

• olopatadine intranasal

  perphenazine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
  
  amitriptyline and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• ondansetron

  perphenazine and ondansetron both increase QTc interval. Avoid or Use Alternate Drug. Avoid with congenital long QT syndrome; ECG monitoring recommended with concomitant medications that prolong QT interval, electrolyte abnormalities, CHF, or bradyarrhythmias.
  
  amitriptyline and ondansetron both increase QTc interval. Avoid or Use Alternate Drug. Avoid with congenital long QT syndrome; ECG monitoring recommended with concomitant medications that prolong QT interval, electrolyte abnormalities, CHF, or bradyarrhythmias.
  
  ondansetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• ozanimod

  ozanimod increases toxicity of amitriptyline by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

• paroxetine

  paroxetine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
  
  perphenazine will increase the level or effect of paroxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
  
  perphenazine and paroxetine both increase QTc interval. Avoid or Use Alternate Drug.

• palonosetron

  palonosetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• paroxetine

  paroxetine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• perphenazine

  perphenazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• phendimetrazine

  amitriptyline, phendimetrazine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• phentermine

  amitriptyline, phentermine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• phenylephrine

  amitriptyline, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• phenylephrine PO

  amitriptyline, phenylephrine PO. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• pirbuterol

  amitriptyline, pirbuterol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• pitolisant

  amitriptyline decreases effects of pitolisant by Other (see comment). Avoid or Use Alternate Drug. Comment: Pitolisant increases histamine levels in the brain; therefore, H1 receptor antagonists that cross the blood-brain barrier may reduce the efficacy of pitolisant.

• pramipexole

  perphenazine decreases effects of pramipexole by pharmacodynamic antagonism. Contraindicated.

• prochlorperazine

  perphenazine and prochlorperazine both increase QTc interval. Avoid or Use Alternate Drug.

• promazine

  promazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  perphenazine and promazine both increase QTc interval. Avoid or Use Alternate Drug.

• promethazine

  perphenazine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.

• propylhexedrine

  amitriptyline, propylhexedrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• protriptyline

  perphenazine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• pseudoephedrine

  amitriptyline increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• quinidine

  quinidine, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Additive cardiac effects.

• quinidine

  quinidine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• ranolazine

  ranolazine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• rasagiline

  rasagiline and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Severe CNS toxicity associated with hyperpyrexia has been reported with the combined treatment of an antidepressant and rasagiline. Avoid combination within 14 days of MAOI use.

• ribociclib

  ribociclib increases toxicity of amitriptyline by QTc interval. Avoid or Use Alternate Drug.
  
  ribociclib increases toxicity of perphenazine by QTc interval. Avoid or Use Alternate Drug.

• ropinirole

  perphenazine decreases effects of ropinirole by pharmacodynamic antagonism. Contraindicated.

• salmeterol

  amitriptyline, salmeterol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• safinamide

  perphenazine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

• saquinavir

  saquinavir, perphenazine. Either increases toxicity of the other by QTc interval. Avoid or Use Alternate Drug. Increased risk of PR or QT prolongation and cardiac arrhythmias.

• selegiline transdermal

  selegiline transdermal and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• selinexor

  selinexor, amitriptyline. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.
  
  selinexor, perphenazine. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

• serdexmethylphenidate/dexmethylphenidate

  amitriptyline, serdexmethylphenidate/dexmethylphenidate. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• sodium oxybate

  perphenazine, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• sertraline

  sertraline and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• sodium oxybate

  amitriptyline, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• St John's Wort

  amitriptyline and St John's Wort both increase serotonin levels. Avoid or Use Alternate Drug.

• sufentanil SL

  sufentanil SL, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• tedizolid

  tedizolid, amitriptyline. Either increases effects of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. both increase serotonin levels; increased risk of serotonin syndrome.

• terbutaline

  amitriptyline, terbutaline. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• tetrabenazine

  tetrabenazine and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.

• thioridazine

  perphenazine and thioridazine both increase QTc interval. Avoid or Use Alternate Drug.
  
  thioridazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  perphenazine will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• toremifene

  amitriptyline and toremifene both increase QTc interval. Avoid or Use Alternate Drug. Concurrent use of toremifene with agents causing QT prolongation should be avoided. If concomitant use is required it's recommended that toremifene be interrupted. If interruption not possible, patients requiring therapy with a drug that prolongs QT should be closely monitored. ECGs should be obtained for high risk patients.

• trazodone

  perphenazine and trazodone both increase QTc interval. Avoid or Use Alternate Drug.

• trazodone

  amitriptyline and trazodone both increase QTc interval. Avoid or Use Alternate Drug.
  
  trazodone and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• tretinoin

  perphenazine, tretinoin. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

• tretinoin topical

  perphenazine, tretinoin topical. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

• trifluoperazine

  perphenazine and trifluoperazine both increase QTc interval. Avoid or Use Alternate Drug.
  
  trifluoperazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• trimipramine

  perphenazine and trimipramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and trimipramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and trimipramine both increase serotonin levels. Avoid or Use Alternate Drug.

• umeclidinium bromide/vilanterol inhaled

  amitriptyline and umeclidinium bromide/vilanterol inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Exercise extreme caution if vilanterol coadministered with MAOIs or TCAs, or within 2 weeks of discontinuation of these drugs; adrenergic agonist effects on the cardiovascular system may be potentiated
  
  amitriptyline increases toxicity of umeclidinium bromide/vilanterol inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.
  
  perphenazine increases toxicity of umeclidinium bromide/vilanterol inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.

• vandetanib

  amitriptyline, vandetanib. Either increases toxicity of the other by QTc interval. Avoid or Use Alternate Drug. Avoid coadministration with drugs known to prolong QT interval; if a drug known to prolong QT interval must be used, more frequent ECG monitoring is recommended.

• venlafaxine

  perphenazine and venlafaxine both increase QTc interval. Avoid or Use Alternate Drug.

• vemurafenib

  vemurafenib and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.

• venlafaxine

  venlafaxine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• vilanterol/fluticasone furoate inhaled

  amitriptyline and vilanterol/fluticasone furoate inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Exercise extreme caution if vilanterol coadministered with MAOIs or TCAs, or within 2 weeks of discontinuation of these drugs; adrenergic agonist effects on the cardiovascular system may be potentiated
  
  amitriptyline increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.
  
  perphenazine increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.

• vilazodone

  amitriptyline, vilazodone. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Concomitant therapy should be discontinued immediately if signs or symptoms of serotonin syndrome emerge and supportive symptomatic treatment should be initiated. .

• yohimbe

  yohimbe decreases effects of perphenazine by pharmacodynamic antagonism. Contraindicated.

• vortioxetine

  amitriptyline, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.

• xylometazoline

  amitriptyline, xylometazoline. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• yohimbe

  yohimbe, amitriptyline. Mechanism: unspecified interaction mechanism. Contraindicated. May cause increase or decrease in blood pressure.

• yohimbine

  amitriptyline, yohimbine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• ziprasidone

  perphenazine and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.

Monitor Closely (527)

• 5-HTP

  amitriptyline and 5-HTP both increase serotonin levels. Modify Therapy/Monitor Closely.

• abiraterone

  abiraterone increases levels of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
  
  abiraterone increases levels of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.

• abobotulinumtoxinA

  abobotulinumtoxinA increases effects of amitriptyline by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects. .
  
  abobotulinumtoxinA increases effects of perphenazine by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects.

• aclidinium

  aclidinium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  aclidinium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine increases effects of aclidinium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• acrivastine

  acrivastine and perphenazine both increase sedation. Use Caution/Monitor.
  
  acrivastine and amitriptyline both increase sedation. Use Caution/Monitor.

• albiglutide

  perphenazine, albiglutide. Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase or decrease glucose levels, monitor therapy closely when these agents are concurrently administered.

• albuterol

  amitriptyline increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  albuterol and amitriptyline both increase QTc interval. Use Caution/Monitor.

• albuterol

  perphenazine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• alfentanil

  alfentanil and perphenazine both increase sedation. Use Caution/Monitor.
  
  alfentanil and amitriptyline both increase sedation. Use Caution/Monitor.

• alfuzosin

  alfuzosin and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  amitriptyline and alfuzosin both increase QTc interval. Use Caution/Monitor.
  
  alfuzosin and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  perphenazine and alfuzosin both increase QTc interval. Use Caution/Monitor.

• almotriptan

  almotriptan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  almotriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• alprazolam

  alprazolam and perphenazine both increase sedation. Use Caution/Monitor.
  
  alprazolam and amitriptyline both increase sedation. Use Caution/Monitor.

• amifampridine

  amitriptyline increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.
  
  perphenazine increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.

• amiodarone

  amiodarone will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• amitriptyline

  perphenazine and amitriptyline both increase sedation. Use Caution/Monitor.

• amisulpride

  amitriptyline and amisulpride both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended if coadministered.
  
  amisulpride and amitriptyline both increase sedation. Use Caution/Monitor.
  
  amisulpride and amitriptyline both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended if coadministered.

• amobarbital

  amobarbital and amitriptyline both increase sedation. Use Caution/Monitor.
  
  amobarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  amobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  amobarbital and perphenazine both increase sedation. Use Caution/Monitor.
  
  amobarbital, amitriptyline. Other (see comment). Use Caution/Monitor. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• amoxapine

  amitriptyline and amoxapine both increase sedation. Use Caution/Monitor.
  
  perphenazine and amoxapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely.
  
  perphenazine and amoxapine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and amoxapine both decrease cholinergic effects/transmission. Use Caution/Monitor.

• anagrelide

  anagrelide and perphenazine both increase QTc interval. Use Caution/Monitor.

• anticholinergic/sedative combos

  anticholinergic/sedative combos and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• anticholinergic/sedative combos

  anticholinergic/sedative combos decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  anticholinergic/sedative combos decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of anticholinergic/sedative combos by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• apomorphine

  apomorphine and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  perphenazine and apomorphine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and apomorphine both increase sedation. Use Caution/Monitor.

• aprepitant

  aprepitant will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• arformoterol

  perphenazine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  arformoterol and perphenazine both increase QTc interval. Use Caution/Monitor.

• arformoterol

  amitriptyline increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  arformoterol and amitriptyline both increase QTc interval. Use Caution/Monitor.

• aripiprazole

  aripiprazole and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  aripiprazole and amitriptyline both increase sedation. Use Caution/Monitor.
  
  aripiprazole and perphenazine both increase sedation. Use Caution/Monitor.
  
  aripiprazole and amitriptyline both increase QTc interval. Use Caution/Monitor.

• armodafinil

  perphenazine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  armodafinil will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  amitriptyline increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• artemether

  artemether and perphenazine both increase QTc interval. Use Caution/Monitor.

• asenapine

  asenapine and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  asenapine and amitriptyline both increase sedation. Use Caution/Monitor.

• artemether/lumefantrine

  artemether/lumefantrine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• asenapine

  asenapine and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  asenapine and perphenazine both increase sedation. Use Caution/Monitor.

• asenapine transdermal

  asenapine transdermal and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  asenapine transdermal and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  asenapine transdermal and amitriptyline both increase sedation. Use Caution/Monitor.
  
  asenapine transdermal and perphenazine both increase sedation. Use Caution/Monitor.

• atazanavir

  atazanavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  atazanavir increases levels of amitriptyline by unspecified interaction mechanism. Use Caution/Monitor.

• atomoxetine

  perphenazine will increase the level or effect of atomoxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  atomoxetine and perphenazine both increase QTc interval. Use Caution/Monitor.

• atomoxetine

  atomoxetine and amitriptyline both increase QTc interval. Use Caution/Monitor.

• atorvastatin

  atorvastatin will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• atracurium

  perphenazine increases effects of atracurium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  atracurium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  atracurium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  atracurium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• atropine

  atropine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  perphenazine increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  atropine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  atropine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• atropine IV/IM

  atropine IV/IM decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  perphenazine increases effects of atropine IV/IM by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  atropine IV/IM decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  atropine IV/IM and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• avapritinib

  avapritinib and amitriptyline both increase sedation. Use Caution/Monitor.
  
  avapritinib and perphenazine both increase sedation. Use Caution/Monitor.

• azelastine

  azelastine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  azelastine and perphenazine both increase sedation. Use Caution/Monitor.

• azithromycin

  perphenazine and azithromycin both increase QTc interval. Use Caution/Monitor.
  
  amitriptyline and azithromycin both increase QTc interval. Use Caution/Monitor.

• baclofen

  baclofen and perphenazine both increase sedation. Use Caution/Monitor.
  
  baclofen and amitriptyline both increase sedation. Use Caution/Monitor.

• bedaquiline

  amitriptyline and bedaquiline both increase QTc interval. Modify Therapy/Monitor Closely. ECG should be monitored closely
  
  perphenazine and bedaquiline both increase QTc interval. Modify Therapy/Monitor Closely. ECG should be monitored closely

• belladonna alkaloids

  perphenazine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  belladonna alkaloids and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.
  
  belladonna alkaloids decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

• belladonna and opium

  belladonna and opium and perphenazine both increase sedation. Use Caution/Monitor.
  
  belladonna and opium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  perphenazine increases effects of belladonna and opium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  belladonna and opium and amitriptyline both increase sedation. Use Caution/Monitor.
  
  belladonna and opium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  belladonna and opium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• benperidol

  benperidol and perphenazine both increase sedation. Use Caution/Monitor.
  
  benperidol and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  benperidol and amitriptyline both increase sedation. Use Caution/Monitor.

• benzhydrocodone/acetaminophen

  benzhydrocodone/acetaminophen, amitriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.
  
  benzhydrocodone/acetaminophen and perphenazine both increase sedation. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of benzhydrocodone/acetaminophen by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone [benzhydrocodone is prodrug of hydrocodone]) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

• benzphetamine

  perphenazine, benzphetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• benztropine

  benztropine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely. Additive anticholinergic adverse effects may be seen with concurrent use.
  
  perphenazine increases effects of benztropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic adverse effects may be seen with concurrent use. .

• bethanechol

  bethanechol increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• brexanolone

  brexanolone, perphenazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brexpiprazole

  brexpiprazole and amitriptyline both increase sedation. Use Caution/Monitor.
  
  brexpiprazole and perphenazine both increase sedation. Use Caution/Monitor.

• brimonidine

  brimonidine and perphenazine both increase sedation. Use Caution/Monitor.
  
  brimonidine and amitriptyline both increase sedation. Use Caution/Monitor.

• brivaracetam

  brivaracetam and amitriptyline both increase sedation. Use Caution/Monitor.
  
  brivaracetam and perphenazine both increase sedation. Use Caution/Monitor.

• brompheniramine

  brompheniramine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  brompheniramine and perphenazine both increase sedation. Use Caution/Monitor.

• buprenorphine

  buprenorphine and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  buprenorphine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  buprenorphine and perphenazine both increase sedation. Use Caution/Monitor.

• buprenorphine buccal

  buprenorphine buccal and amitriptyline both increase sedation. Use Caution/Monitor.
  
  buprenorphine buccal and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  buprenorphine buccal and perphenazine both increase sedation. Use Caution/Monitor.

• buprenorphine subdermal implant

  buprenorphine subdermal implant and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  amitriptyline, buprenorphine subdermal implant. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.
  
  buprenorphine subdermal implant and perphenazine both increase sedation. Use Caution/Monitor.

• buprenorphine transdermal

  buprenorphine transdermal and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  buprenorphine transdermal and perphenazine both increase sedation. Use Caution/Monitor.

• buprenorphine, long-acting injection

  amitriptyline, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

• buprenorphine, long-acting injection

  perphenazine increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.
  
  buprenorphine, long-acting injection and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  buprenorphine, long-acting injection and perphenazine both increase sedation. Use Caution/Monitor.

• bupropion

  bupropion will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  bupropion will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  perphenazine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.
  
  amitriptyline increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

• butabarbital

  butabarbital and perphenazine both increase sedation. Use Caution/Monitor.
  
  butabarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  butabarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  butabarbital and amitriptyline both increase sedation. Use Caution/Monitor.

• butalbital

  butalbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  butalbital and perphenazine both increase sedation. Use Caution/Monitor.
  
  butalbital and amitriptyline both increase sedation. Use Caution/Monitor.

• butorphanol

  butorphanol and perphenazine both increase sedation. Use Caution/Monitor.
  
  butorphanol and amitriptyline both increase sedation. Use Caution/Monitor.

• caffeine

  perphenazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• carbachol

  carbachol increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• carbinoxamine

  carbinoxamine and perphenazine both increase sedation. Use Caution/Monitor.

• carbamazepine

  carbamazepine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• carbinoxamine

  carbinoxamine and amitriptyline both increase sedation. Use Caution/Monitor.

• carisoprodol

  carisoprodol and amitriptyline both increase sedation. Use Caution/Monitor.
  
  carisoprodol and perphenazine both increase sedation. Use Caution/Monitor.

• carvedilol

  perphenazine will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• cenobamate

  cenobamate, amitriptyline. Either increases effects of the other by sedation. Use Caution/Monitor.

• cenobamate

  cenobamate, perphenazine. Either increases effects of the other by sedation. Use Caution/Monitor.

• ceritinib

  ceritinib and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  ceritinib and amitriptyline both increase QTc interval. Use Caution/Monitor.

• cevimeline

  cevimeline increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• chloral hydrate

  chloral hydrate and perphenazine both increase sedation. Use Caution/Monitor.

• chloral hydrate

  chloral hydrate and amitriptyline both increase sedation. Use Caution/Monitor.

• chlordiazepoxide

  chlordiazepoxide and perphenazine both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and amitriptyline both increase sedation. Use Caution/Monitor.

• chloroquine

  chloroquine increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor.

• chlorpheniramine

  chlorpheniramine and perphenazine both increase sedation. Use Caution/Monitor.

• chlorpheniramine

  chlorpheniramine and amitriptyline both increase sedation. Use Caution/Monitor.

• chlorpromazine

  chlorpromazine and perphenazine both increase sedation. Use Caution/Monitor.
  
  chlorpromazine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  chlorpromazine and amitriptyline both increase sedation. Use Caution/Monitor.

• chlorzoxazone

  chlorzoxazone and perphenazine both increase sedation. Use Caution/Monitor.
  
  chlorzoxazone and amitriptyline both increase sedation. Use Caution/Monitor.

• cigarette smoking

  cigarette smoking decreases levels of perphenazine by increasing metabolism. Use Caution/Monitor. Interaction mainly seen w/chlorpromazine & thioridazine, but may occur w/other phenothiazines.

• cimetidine

  cimetidine will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cinnarizine

  cinnarizine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  cinnarizine and perphenazine both increase sedation. Use Caution/Monitor.

• cisatracurium

  cisatracurium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  cisatracurium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of cisatracurium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  cisatracurium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• citalopram

  citalopram and perphenazine both increase QTc interval. Use Caution/Monitor.

• clarithromycin

  clarithromycin will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• clemastine

  clemastine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  clemastine and perphenazine both increase sedation. Use Caution/Monitor.

• clobazam

  amitriptyline, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
  
  clobazam will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly.
  
  clobazam will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly.

• clomipramine

  amitriptyline and clomipramine both increase sedation. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  amitriptyline and clomipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine and clomipramine both increase sedation. Use Caution/Monitor.

• clonazepam

  clonazepam and perphenazine both increase sedation. Use Caution/Monitor.
  
  clonazepam and amitriptyline both increase sedation. Use Caution/Monitor.

• clonidine

  clonidine, perphenazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• clorazepate

  clorazepate and amitriptyline both increase sedation. Use Caution/Monitor.

• clorazepate

  clorazepate and perphenazine both increase sedation. Use Caution/Monitor.

• clotrimazole

  clotrimazole will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• clozapine

  clozapine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  clozapine and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  clozapine and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  clozapine and perphenazine both increase sedation. Use Caution/Monitor.

• cobicistat

  cobicistat will increase the level or effect of perphenazine by Other (see comment). Modify Therapy/Monitor Closely. A decrease in the dose of antipsychotics that are metabolized by CYP3A or CYP2D6 may be needed upon coadministration.
  
  cobicistat will increase the level or effect of amitriptyline by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.
  
  cobicistat will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Carefully titrate antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant response

• cocaine topical

  amitriptyline and cocaine topical both increase serotonin levels. Modify Therapy/Monitor Closely.

• codeine

  codeine and perphenazine both increase sedation. Use Caution/Monitor.

• codeine

  codeine and amitriptyline both increase sedation. Use Caution/Monitor.

• conivaptan

  conivaptan will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• crizotinib

  crizotinib and amitriptyline both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.
  
  crizotinib and perphenazine both increase QTc interval. Use Caution/Monitor.

• cyclizine

  cyclizine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  cyclizine and perphenazine both increase sedation. Use Caution/Monitor.
  
  cyclizine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine increases effects of cyclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  cyclizine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  cyclizine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

• cyclobenzaprine

  cyclobenzaprine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  cyclobenzaprine and perphenazine both increase sedation. Use Caution/Monitor.
  
  perphenazine increases effects of cyclobenzaprine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  cyclobenzaprine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  cyclobenzaprine and amitriptyline both increase sedation. Use Caution/Monitor.

• cyclosporine

  cyclosporine will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  cyclosporine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• cyproheptadine

  cyproheptadine and perphenazine both increase sedation. Use Caution/Monitor.

• cyproheptadine

  cyproheptadine and amitriptyline both increase sedation. Use Caution/Monitor.

• dantrolene

  dantrolene and perphenazine both increase sedation. Use Caution/Monitor.
  
  dantrolene and amitriptyline both increase sedation. Use Caution/Monitor.

• daridorexant

  perphenazine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
  
  amitriptyline and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• darifenacin

  darifenacin will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  darifenacin decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  perphenazine increases effects of darifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  darifenacin decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  darifenacin and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• darunavir

  darunavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with SSRIs, TCAs, or trazodone may require dose titration of antidepressant to desired effect (eg, using the lowest feasible initial or maintenance dose). Monitor for antidepressant response.

• dasatinib

  perphenazine and dasatinib both increase QTc interval. Modify Therapy/Monitor Closely.

• dasatinib

  amitriptyline and dasatinib both increase QTc interval. Modify Therapy/Monitor Closely.

• debrisoquine

  amitriptyline decreases effects of debrisoquine by Other (see comment). Use Caution/Monitor. Comment: Inhibition of uptake by adrenergic neurons.

• degarelix

  degarelix and amitriptyline both increase QTc interval. Use Caution/Monitor.

• desflurane

  desflurane and amitriptyline both increase sedation. Use Caution/Monitor.
  
  desflurane and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  desflurane and perphenazine both increase sedation. Use Caution/Monitor.
  
  desflurane and amitriptyline both increase QTc interval. Use Caution/Monitor.

• desipramine

  amitriptyline and desipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of desipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  perphenazine and desipramine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and desipramine both increase sedation. Use Caution/Monitor.

• desvenlafaxine

  desvenlafaxine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

• deutetrabenazine

  amitriptyline and deutetrabenazine both increase sedation. Use Caution/Monitor.
  
  deutetrabenazine and amitriptyline both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).

• deutetrabenazine

  perphenazine and deutetrabenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely. The risk for parkinsonism, neuroleptic malignant syndrome, and akathisia may be increased by concomitant use of deutetrabenazine and dopamine antagonists or antipsychotics.
  
  perphenazine and deutetrabenazine both increase sedation. Use Caution/Monitor.
  
  deutetrabenazine and perphenazine both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).

• dexchlorpheniramine

  dexchlorpheniramine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  dexchlorpheniramine and perphenazine both increase sedation. Use Caution/Monitor.

• dexfenfluramine

  perphenazine, dexfenfluramine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  amitriptyline and dexfenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  perphenazine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dexmedetomidine

  dexmedetomidine and perphenazine both increase sedation. Use Caution/Monitor.
  
  dexmedetomidine and amitriptyline both increase sedation. Use Caution/Monitor.

• dexmethylphenidate

  perphenazine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine, dexmethylphenidate. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• dextroamphetamine

  amitriptyline increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline and dextroamphetamine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  perphenazine, dextroamphetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  amitriptyline increases effects of dextroamphetamine by unknown mechanism. Use Caution/Monitor.
  
  perphenazine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dextroamphetamine transdermal

  amitriptyline will increase the level or effect of dextroamphetamine transdermal by pharmacodynamic synergism. Modify Therapy/Monitor Closely. May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in dextroamphetamine levels in brain; May be potentiate cardiovascular effects. Monitor frequently and adjust or use an alternant based on clinical response.
  
  perphenazine, dextroamphetamine transdermal. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine transdermal and concomitant serotonergic drug(s).

• dextromethorphan

  dextromethorphan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• dextromoramide

  dextromoramide and amitriptyline both increase sedation. Use Caution/Monitor.

• dextromoramide

  dextromoramide and perphenazine both increase sedation. Use Caution/Monitor.

• diamorphine

  diamorphine and perphenazine both increase sedation. Use Caution/Monitor.
  
  diamorphine and amitriptyline both increase sedation. Use Caution/Monitor.

• diazepam

  diazepam and perphenazine both increase sedation. Use Caution/Monitor.
  
  diazepam and amitriptyline both increase sedation. Use Caution/Monitor.

• diazepam intranasal

  diazepam intranasal, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.

• dicyclomine

  dicyclomine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  dicyclomine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of dicyclomine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• dicyclomine

  dicyclomine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• diethylpropion

  perphenazine, diethylpropion. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• difelikefalin

  difelikefalin and perphenazine both increase sedation. Use Caution/Monitor.
  
  difelikefalin and amitriptyline both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  difenoxin hcl and perphenazine both increase sedation. Use Caution/Monitor.
  
  difenoxin hcl and amitriptyline both increase sedation. Use Caution/Monitor.

• dihydroergotamine

  dihydroergotamine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  amitriptyline and dihydroergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• dihydroergotamine intranasal

  amitriptyline and dihydroergotamine intranasal both increase serotonin levels. Modify Therapy/Monitor Closely.

• dimenhydrinate

  dimenhydrinate and perphenazine both increase sedation. Use Caution/Monitor.

• diltiazem

  diltiazem will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use with amitriptyline may alter blood pressure control.

• dimenhydrinate

  dimenhydrinate and amitriptyline both increase sedation. Use Caution/Monitor.

• diphenhydramine

  perphenazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.
  
  diphenhydramine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine and perphenazine both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

• diphenoxylate hcl

  diphenoxylate hcl and perphenazine both increase sedation. Use Caution/Monitor.
  
  diphenoxylate hcl and amitriptyline both increase sedation. Use Caution/Monitor.

• dipipanone

  dipipanone and perphenazine both increase sedation. Use Caution/Monitor.
  
  dipipanone and amitriptyline both increase sedation. Use Caution/Monitor.

• dobutamine

  perphenazine, dobutamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dofetilide

  dofetilide increases toxicity of perphenazine by QTc interval. Use Caution/Monitor.
  
  dofetilide increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor.

• dolasetron

  perphenazine and dolasetron both increase QTc interval. Modify Therapy/Monitor Closely.
  
  amitriptyline and dolasetron both increase QTc interval. Modify Therapy/Monitor Closely.

• donepezil

  donepezil and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  donepezil increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
  
  donepezil and perphenazine both increase QTc interval. Use Caution/Monitor.

• donepezil transdermal

  donepezil transdermal, perphenazine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

• dopamine

  amitriptyline increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dopamine

  perphenazine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine, dopamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• dopexamine

  perphenazine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dosulepin

  amitriptyline and dosulepin both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine and dosulepin both increase sedation. Use Caution/Monitor.
  
  amitriptyline and dosulepin both increase sedation. Use Caution/Monitor.

• doxepin

  perphenazine and doxepin both increase sedation. Use Caution/Monitor.
  
  amitriptyline and doxepin both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  amitriptyline and doxepin both increase sedation. Use Caution/Monitor.

• doxylamine

  doxylamine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  doxylamine and perphenazine both increase sedation. Use Caution/Monitor.

• droperidol

  droperidol and perphenazine both increase sedation. Use Caution/Monitor.
  
  droperidol and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  droperidol and amitriptyline both increase sedation. Use Caution/Monitor.

• duloxetine

  perphenazine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• echothiophate iodide

  echothiophate iodide increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• efavirenz

  efavirenz and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  efavirenz and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  efavirenz will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  efavirenz will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• elagolix

  elagolix will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• eletriptan

  eletriptan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• eletriptan

  eletriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• eliglustat

  eliglustat and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  eliglustat and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  eliglustat increases levels of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the concomitant drug and titrate to clinical effect.
  
  eliglustat increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.
  
  eliglustat increases levels of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the concomitant drug and titrate to clinical effect.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; A decrease in dose of the neuroleptic may be needed when coadministered.
  
  elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

• encorafenib

  encorafenib and perphenazine both increase QTc interval. Use Caution/Monitor.

• entrectinib

  entrectinib and amitriptyline both increase QTc interval. Use Caution/Monitor.

• entrectinib

  entrectinib and perphenazine both increase QTc interval. Use Caution/Monitor.

• ephedrine

  perphenazine, ephedrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases effects of ephedrine by unknown mechanism. Use Caution/Monitor.
  
  amitriptyline increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• epinephrine

  amitriptyline increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases effects of epinephrine by unknown mechanism. Use Caution/Monitor.
  
  perphenazine decreases effects of epinephrine by pharmacodynamic antagonism. Use Caution/Monitor. Block pressor response to epinephrine, which may result in severe hypotension and tachycardia.
  
  perphenazine increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine, epinephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• epinephrine inhaled

  amitriptyline and epinephrine inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Tricyclic antidepressants may potentiate epinephrine effect on cardiovascular system.

• epinephrine racemic

  perphenazine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine decreases effects of epinephrine racemic by pharmacodynamic antagonism. Use Caution/Monitor. Block pressor response to epinephrine, which may result in severe hypotension and tachycardia.

• epinephrine racemic

  amitriptyline increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases effects of epinephrine racemic by unknown mechanism. Use Caution/Monitor.

• ergoloid mesylates

  ergoloid mesylates, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• ergotamine

  ergotamine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  amitriptyline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• eribulin

  eribulin and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  eribulin and perphenazine both increase QTc interval. Use Caution/Monitor.

• escitalopram

  escitalopram increases toxicity of perphenazine by QTc interval. Use Caution/Monitor.

• esketamine intranasal

  esketamine intranasal, amitriptyline. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• eslicarbazepine acetate

  eslicarbazepine acetate will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• esomeprazole

  esomeprazole will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• estazolam

  estazolam and amitriptyline both increase sedation. Use Caution/Monitor.
  
  estazolam and perphenazine both increase sedation. Use Caution/Monitor.

• ethanol

  perphenazine and ethanol both increase sedation. Use Caution/Monitor.
  
  amitriptyline and ethanol both increase sedation. Use Caution/Monitor.

• etomidate

  etomidate and amitriptyline both increase sedation. Use Caution/Monitor.
  
  etomidate and perphenazine both increase sedation. Use Caution/Monitor.

• etravirine

  etravirine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• fedratinib

  fedratinib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

• ezogabine

  ezogabine, amitriptyline. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.

• fedratinib

  fedratinib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

• felbamate

  felbamate will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• felodipine

  felodipine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• fenfluramine

  perphenazine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline and fenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  perphenazine, fenfluramine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  fenfluramine, amitriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration with drugs that increase serotoninergic effects may increase the risk of serotonin syndrome.

• fentanyl

  fentanyl, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• fesoterodine

  fesoterodine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• fesoterodine

  fesoterodine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  fesoterodine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of fesoterodine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• fingolimod

  fingolimod and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  fingolimod and amitriptyline both increase QTc interval. Use Caution/Monitor.

• flavoxate

  perphenazine increases effects of flavoxate by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  flavoxate and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.
  
  flavoxate decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  flavoxate decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

• flecainide

  amitriptyline and flecainide both increase QTc interval. Modify Therapy/Monitor Closely.
  
  perphenazine will increase the level or effect of flecainide by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  perphenazine and flecainide both increase QTc interval. Modify Therapy/Monitor Closely.

• flibanserin

  flibanserin, perphenazine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• fluconazole

  fluconazole will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  fluconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fluoxetine

  amitriptyline and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely.

• fluphenazine

  fluphenazine and perphenazine both increase sedation. Use Caution/Monitor.
  
  fluphenazine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  fluphenazine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

• flurazepam

  flurazepam and perphenazine both increase sedation. Use Caution/Monitor.
  
  flurazepam and amitriptyline both increase sedation. Use Caution/Monitor.

• fluvoxamine

  fluvoxamine and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  fluvoxamine and amitriptyline both increase QTc interval. Modify Therapy/Monitor Closely.

• formoterol

  perphenazine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• fosamprenavir

  fosamprenavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• foscarnet

  perphenazine and foscarnet both increase QTc interval. Modify Therapy/Monitor Closely.

• fosaprepitant

  fosaprepitant will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• foscarnet

  amitriptyline and foscarnet both increase QTc interval. Modify Therapy/Monitor Closely.

• fosphenytoin

  fosphenytoin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  fosphenytoin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• fostemsavir

  amitriptyline and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

• frovatriptan

  frovatriptan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  frovatriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• gabapentin

  gabapentin, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• ganaxolone

  perphenazine and ganaxolone both increase sedation. Use Caution/Monitor.

• gabapentin enacarbil

  gabapentin enacarbil, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• galantamine

  galantamine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• ganaxolone

  amitriptyline and ganaxolone both increase sedation. Use Caution/Monitor.

• gemifloxacin

  gemifloxacin and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  gemifloxacin and amitriptyline both increase QTc interval. Use Caution/Monitor.

• gilteritinib

  gilteritinib and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  gilteritinib and perphenazine both increase QTc interval. Use Caution/Monitor.

• glecaprevir/pibrentasvir

  glecaprevir/pibrentasvir will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

• glycopyrrolate

  perphenazine increases toxicity of glycopyrrolate by unknown mechanism. Use Caution/Monitor.
  
  perphenazine increases effects of glycopyrrolate by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• glycopyrrolate

  glycopyrrolate and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.
  
  amitriptyline increases levels of glycopyrrolate by unknown mechanism. Use Caution/Monitor.

• glycopyrrolate inhaled

  perphenazine increases toxicity of glycopyrrolate inhaled by unknown mechanism. Use Caution/Monitor.
  
  glycopyrrolate inhaled decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of glycopyrrolate inhaled by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  glycopyrrolate inhaled decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  amitriptyline increases levels of glycopyrrolate inhaled by unknown mechanism. Use Caution/Monitor.
  
  glycopyrrolate inhaled and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• glycopyrronium tosylate topical

  glycopyrronium tosylate topical, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of glycopyrronium tosylate topical with other anticholinergic medications may result in additive anticholinergic adverse effects.
  
  glycopyrronium tosylate topical, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of glycopyrronium tosylate topical with other anticholinergic medications may result in additive anticholinergic adverse effects.

• granisetron

  granisetron and perphenazine both increase QTc interval. Use Caution/Monitor.

• grapefruit

  grapefruit will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• guanfacine

  guanfacine, perphenazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• haloperidol

  haloperidol and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  haloperidol and amitriptyline both increase sedation. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of haloperidol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  haloperidol and perphenazine both increase sedation. Use Caution/Monitor.

• henbane

  henbane decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  henbane decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  henbane and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine increases effects of henbane by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• homatropine

  homatropine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  homatropine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  homatropine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• huperzine A

  huperzine A increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• hydrocodone

  perphenazine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.

• hydrocodone

  hydrocodone, amitriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

• hydromorphone

  perphenazine will increase the level or effect of hydromorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  hydromorphone and perphenazine both increase sedation. Use Caution/Monitor.
  
  hydromorphone and amitriptyline both increase sedation. Use Caution/Monitor.

• hydroxyzine

  hydroxyzine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  hydroxyzine and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  hydroxyzine and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  hydroxyzine and perphenazine both increase sedation. Use Caution/Monitor.

• hyoscyamine

  hyoscyamine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  hyoscyamine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  hyoscyamine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of hyoscyamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• hyoscyamine spray

  perphenazine increases effects of hyoscyamine spray by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  hyoscyamine spray and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  hyoscyamine spray decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  hyoscyamine spray decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• iloperidone

  perphenazine and iloperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  iloperidone and perphenazine both increase sedation. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of iloperidone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  amitriptyline and iloperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  iloperidone and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  iloperidone and amitriptyline both increase sedation. Use Caution/Monitor.

• imipramine

  amitriptyline and imipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine and imipramine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and imipramine both increase sedation. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• incobotulinumtoxinA

  perphenazine, incobotulinumtoxinA. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects.

• indacaterol, inhaled

  indacaterol, inhaled, amitriptyline. QTc interval. Use Caution/Monitor. Indacaterol should be administered with extreme caution to patients treated with TCAs. Drugs that are known to prolong the QTc interval may have an increased the risk of ventricular arrhythmias.

• indacaterol, inhaled

  indacaterol, inhaled, perphenazine. QTc interval. Use Caution/Monitor. Drugs that are known to prolong the QTc interval may have an increased the risk of ventricular arrhythmias.

• indinavir

  indinavir will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• insulin degludec

  perphenazine decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

• insulin degludec/insulin aspart

  perphenazine decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

• insulin inhaled

  perphenazine decreases effects of insulin inhaled by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

• ipratropium

  ipratropium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. Due to the poor systemic absorption of ipratropium, interaction unlikely at regularly recommended dosages.
  
  ipratropium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  ipratropium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of ipratropium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• isoflurane

  isoflurane and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  isoflurane and perphenazine both increase QTc interval. Use Caution/Monitor.

• isoniazid

  isoniazid will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  amitriptyline and isoniazid both increase serotonin levels. Modify Therapy/Monitor Closely.

• isoproterenol

  perphenazine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine, isoproterenol. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• isoproterenol

  amitriptyline increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• istradefylline

  istradefylline will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

• itraconazole

  itraconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  itraconazole and amitriptyline both increase QTc interval. Use Caution/Monitor.

• ivacaftor

  ivacaftor increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

• ketamine

  ketamine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  ketamine and perphenazine both increase sedation. Use Caution/Monitor.

• ketoconazole

  ketoconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• ketotifen, ophthalmic

  perphenazine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

• ketotifen, ophthalmic

  amitriptyline and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

• L-tryptophan

  amitriptyline and L-tryptophan both increase serotonin levels. Modify Therapy/Monitor Closely.

• lapatinib

  amitriptyline and lapatinib both increase QTc interval. Modify Therapy/Monitor Closely.
  
  perphenazine and lapatinib both increase QTc interval. Modify Therapy/Monitor Closely.

• lasmiditan

  lasmiditan, amitriptyline. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.
  
  lasmiditan, perphenazine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.
  
  amitriptyline increases effects of lasmiditan by serotonin levels. Use Caution/Monitor. Coadministration may increase risk of serotonin syndrome.

• lemborexant

  lemborexant, perphenazine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.
  
  lemborexant, amitriptyline. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

• letermovir

  letermovir increases levels of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levalbuterol

  perphenazine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• levalbuterol

  amitriptyline increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• levofloxacin

  amitriptyline and levofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.
  
  perphenazine and levofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

• levoketoconazole

  levoketoconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  levoketoconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• levomilnacipran

  levomilnacipran, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• levorphanol

  levorphanol and amitriptyline both increase sedation. Use Caution/Monitor.
  
  levorphanol and perphenazine both increase sedation. Use Caution/Monitor.

• levothyroxine

  levothyroxine increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• linezolid

  linezolid, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• liothyronine

  liothyronine increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• liotrix

  liotrix increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• liraglutide

  perphenazine, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase or decrease glucose levels, monitor therapy closely when these agents are concurrently administered.

• lisdexamfetamine

  amitriptyline increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline, lisdexamfetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue along with concomitant serotonergic drug(s).
  
  perphenazine, lisdexamfetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• lithium

  lithium and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  lithium and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  lithium, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  amitriptyline and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  lithium, perphenazine. Other (see comment). Use Caution/Monitor. Comment: Risk of neurotoxicity. Multiple mechanisms involved.

• lofepramine

  perphenazine and lofepramine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and lofepramine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and lofepramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of lofepramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• lofexidine

  perphenazine and lofexidine both increase sedation. Use Caution/Monitor.
  
  amitriptyline decreases effects of lofexidine by unspecified interaction mechanism. Use Caution/Monitor.
  
  amitriptyline and lofexidine both increase sedation. Use Caution/Monitor.

• loprazolam

  loprazolam and amitriptyline both increase sedation. Use Caution/Monitor.
  
  loprazolam and perphenazine both increase sedation. Use Caution/Monitor.

• loratadine

  loratadine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• lorazepam

  lorazepam and perphenazine both increase sedation. Use Caution/Monitor.

• lorazepam

  lorazepam and amitriptyline both increase sedation. Use Caution/Monitor.

• lorcaserin

  lorcaserin will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  lorcaserin will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  lorcaserin, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• lormetazepam

  lormetazepam and perphenazine both increase sedation. Use Caution/Monitor.
  
  lormetazepam and amitriptyline both increase sedation. Use Caution/Monitor.

• loxapine

  loxapine and perphenazine both increase sedation. Use Caution/Monitor.
  
  loxapine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  loxapine and amitriptyline both increase sedation. Use Caution/Monitor.

• loxapine inhaled

  loxapine inhaled and perphenazine both increase sedation. Use Caution/Monitor.
  
  loxapine inhaled and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  loxapine inhaled and amitriptyline both increase sedation. Use Caution/Monitor.

• lsd

  amitriptyline and lsd both increase serotonin levels. Modify Therapy/Monitor Closely.

• lumefantrine

  lumefantrine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• lurasidone

  lurasidone, amitriptyline. Either increases toxicity of the other by sedation. Use Caution/Monitor. Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.
  
  lurasidone, perphenazine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.
  
  lurasidone increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of hypotension with concurrent use. Monitor blood pressure and adjust dose of antihypertensive agent as needed.

• maprotiline

  perphenazine and maprotiline both increase sedation. Use Caution/Monitor.
  
  amitriptyline and maprotiline both increase sedation. Use Caution/Monitor.
  
  amitriptyline and maprotiline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• maraviroc

  maraviroc, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.

• marijuana

  perphenazine and marijuana both increase sedation. Use Caution/Monitor.

• marijuana

  amitriptyline and marijuana both increase sedation. Use Caution/Monitor.

• mavacamten

  amitriptyline will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

• meclizine

  meclizine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  meclizine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of meclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  meclizine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• melatonin

  perphenazine and melatonin both increase sedation. Use Caution/Monitor.
  
  amitriptyline and melatonin both increase sedation. Use Caution/Monitor.

• meperidine

  meperidine and perphenazine both increase sedation. Use Caution/Monitor.
  
  meperidine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  meperidine and amitriptyline both increase sedation. Use Caution/Monitor.

• meprobamate

  amitriptyline and meprobamate both increase sedation. Use Caution/Monitor.
  
  perphenazine and meprobamate both increase sedation. Use Caution/Monitor.

• metaproterenol

  perphenazine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• metaxalone

  metaxalone and amitriptyline both increase sedation. Use Caution/Monitor.
  
  metaxalone and perphenazine both increase sedation. Use Caution/Monitor.

• metformin

  perphenazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• methadone

  amitriptyline and methadone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  methadone and amitriptyline both increase sedation. Use Caution/Monitor.

• methadone

  perphenazine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  methadone and perphenazine both increase sedation. Use Caution/Monitor.
  
  methadone, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• methamphetamine

  perphenazine, methamphetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• methocarbamol

  methocarbamol and perphenazine both increase sedation. Use Caution/Monitor.
  
  methocarbamol and amitriptyline both increase sedation. Use Caution/Monitor.

• methoxsalen

  methoxsalen, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive photosensitizing effects.

• methscopolamine

  methscopolamine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• methscopolamine

  methscopolamine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  methscopolamine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of methscopolamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• methylenedioxymethamphetamine

  perphenazine, methylenedioxymethamphetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• methylergonovine

  methylergonovine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• methylphenidate

  amitriptyline, methylphenidate. Other (see comment). Use Caution/Monitor. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• methylphenidate

  perphenazine, methylphenidate. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases toxicity of methylphenidate by pharmacodynamic antagonism. Use Caution/Monitor. Closely monitor for signs of altered clinical response to either methylphenidate or an antipsychotic when using these drugs in combination.

• methylphenidate transdermal

  methylphenidate transdermal will increase the level or effect of amitriptyline by decreasing elimination. Modify Therapy/Monitor Closely. Consider decreasing the dose of these drugs when given coadministered with methylphenidate. Monitor for drug toxiticities when initiating or discontinuing methylphenidate.

• metoclopramide

  perphenazine and metoclopramide both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

• metoprolol

  perphenazine will increase the level or effect of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• mexiletine

  perphenazine will increase the level or effect of mexiletine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• midazolam

  midazolam and perphenazine both increase sedation. Use Caution/Monitor.
  
  midazolam and amitriptyline both increase sedation. Use Caution/Monitor.

• midazolam intranasal

  midazolam intranasal, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.
  
  midazolam intranasal, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

• midodrine

  perphenazine, midodrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• mifepristone

  mifepristone, perphenazine. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.
  
  mifepristone, amitriptyline. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.

• milnacipran

  milnacipran, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• mipomersen

  mipomersen, amitriptyline. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

• mirabegron

  mirabegron will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  mirabegron will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• mirtazapine

  perphenazine and mirtazapine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  amitriptyline and mirtazapine both increase sedation. Use Caution/Monitor.
  
  mirtazapine and perphenazine both increase QTc interval. Use Caution/Monitor.

• modafinil

  perphenazine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  modafinil will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• morphine

  perphenazine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  amitriptyline and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  morphine and perphenazine both increase sedation. Use Caution/Monitor.
  
  morphine and amitriptyline both increase sedation. Use Caution/Monitor.

• motherwort

  perphenazine and motherwort both increase sedation. Use Caution/Monitor.
  
  amitriptyline and motherwort both increase sedation. Use Caution/Monitor.

• moxonidine

  perphenazine and moxonidine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and moxonidine both increase sedation. Use Caution/Monitor.

• nabilone

  perphenazine and nabilone both increase sedation. Use Caution/Monitor.
  
  amitriptyline and nabilone both increase sedation. Use Caution/Monitor.

• nalbuphine

  nalbuphine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  nalbuphine and perphenazine both increase sedation. Use Caution/Monitor.

• naratriptan

  naratriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  naratriptan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• nebivolol

  perphenazine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• nefazodone

  nefazodone will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  nefazodone will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• nefopam

  nefopam, amitriptyline. Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Use combination with caution.

• nelfinavir

  nelfinavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• neostigmine

  neostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• nicardipine

  nicardipine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• nifedipine

  nifedipine will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• norepinephrine

  perphenazine, norepinephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  amitriptyline increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases effects of norepinephrine by unknown mechanism. Use Caution/Monitor.

• nortriptyline

  amitriptyline and nortriptyline both increase sedation. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  amitriptyline and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine and nortriptyline both increase sedation. Use Caution/Monitor.

• ofloxacin

  amitriptyline and ofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.
  
  perphenazine and ofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

• olanzapine

  olanzapine and perphenazine both increase sedation. Use Caution/Monitor.
  
  olanzapine and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  olanzapine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  olanzapine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  olanzapine and perphenazine both increase QTc interval. Use Caution/Monitor.

• oliceridine

  amitriptyline, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely.
  
  oliceridine, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).
  
  amitriptyline increases toxicity of oliceridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor for signs of urinary retention or reduced gastric motility if oliceridine is coadministered with anticholinergics.

• olodaterol inhaled

  amitriptyline and olodaterol inhaled both increase QTc interval. Use Caution/Monitor. TCAs prolong the QTc interval and may potentiate the effects of beta2 agonists on the cardiovascular system; increased risk of ventricular arrhythmias
  
  perphenazine and olodaterol inhaled both increase QTc interval. Use Caution/Monitor. Drugs that prolong the QTc interval and may potentiate the effects of beta2 agonists on the cardiovascular system; increased risk of ventricular arrhythmias

• onabotulinumtoxinA

  onabotulinumtoxinA and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.
  
  onabotulinumtoxinA decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  onabotulinumtoxinA decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of onabotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• opium tincture

  opium tincture and perphenazine both increase sedation. Use Caution/Monitor.
  
  opium tincture and amitriptyline both increase sedation. Use Caution/Monitor.

• orphenadrine

  amitriptyline and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  orphenadrine and perphenazine both increase sedation. Use Caution/Monitor.
  
  orphenadrine and amitriptyline both increase sedation. Use Caution/Monitor.

• osilodrostat

  osilodrostat and amitriptyline both increase QTc interval. Use Caution/Monitor.

• osimertinib

  osimertinib and perphenazine both increase QTc interval. Use Caution/Monitor. Conduct periodic monitoring with ECGs and electrolytes in patients taking drugs known to prolong the QTc interval.

• osimertinib

  osimertinib and amitriptyline both increase QTc interval. Use Caution/Monitor. Conduct periodic monitoring with ECGs and electrolytes in patients taking drugs known to prolong the QTc interval.

• oxaliplatin

  oxaliplatin will increase the level or effect of amitriptyline by Other (see comment). Use Caution/Monitor. Monitor for ECG changes if therapy is initiated in patients with drugs known to prolong QT interval.
  
  oxaliplatin and perphenazine both increase QTc interval. Use Caution/Monitor.

• oxazepam

  oxazepam and perphenazine both increase sedation. Use Caution/Monitor.
  
  oxazepam and amitriptyline both increase sedation. Use Caution/Monitor.

• oxybutynin

  oxybutynin decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  oxybutynin decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  perphenazine increases effects of oxybutynin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  oxybutynin and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• oxybutynin topical

  oxybutynin topical decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  perphenazine increases effects of oxybutynin topical by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  oxybutynin topical and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  oxybutynin topical decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

• oxybutynin transdermal

  oxybutynin transdermal decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  oxybutynin transdermal decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  perphenazine increases effects of oxybutynin transdermal by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  oxybutynin transdermal and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• oxycodone

  oxycodone and perphenazine both increase sedation. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  oxycodone and amitriptyline both increase sedation. Use Caution/Monitor.

• oxymetazoline intranasal

  amitriptyline increases effects of oxymetazoline intranasal by pharmacodynamic synergism. Use Caution/Monitor. TCAs inhibit norepinephrine uptake in adrenergic neurons, thereby increasing synaptic norepinephrine levels. Coadministration with alpha1 agonists may cause increased adrenergic receptor stimulation. When oxymetazoline is combined with intranasal tetracaine for dental anesthesia, avoid or use alternant anesthetic in patients taking TCAs.

• oxymorphone

  perphenazine will increase the level or effect of oxymorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  oxymorphone and perphenazine both increase sedation. Use Caution/Monitor.

• oxymorphone

  oxymorphone and amitriptyline both increase sedation. Use Caution/Monitor.

• ozanimod

  ozanimod and perphenazine both increase QTc interval. Modify Therapy/Monitor Closely. The potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties.
  
  ozanimod and amitriptyline both increase QTc interval. Modify Therapy/Monitor Closely. The potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties.

• paliperidone

  amitriptyline and paliperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  paliperidone and perphenazine both increase sedation. Use Caution/Monitor.
  
  paliperidone and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  paliperidone and amitriptyline both increase sedation. Use Caution/Monitor.
  
  perphenazine and paliperidone both increase QTc interval. Modify Therapy/Monitor Closely.

• pancuronium

  pancuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine increases effects of pancuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  pancuronium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  pancuronium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• panobinostat

  panobinostat will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Panobinostat can increase the levels and effects of sensitive CYP2D6 substrates or those with a narrow therapeutic index CYP2D6.

• papaveretum

  papaveretum and amitriptyline both increase sedation. Use Caution/Monitor.

• papaveretum

  papaveretum and perphenazine both increase sedation. Use Caution/Monitor.

• papaverine

  perphenazine and papaverine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and papaverine both increase sedation. Use Caution/Monitor.

• paroxetine

  paroxetine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  amitriptyline and paroxetine both increase QTc interval. Modify Therapy/Monitor Closely.

• pasireotide

  amitriptyline and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.
  
  perphenazine and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.

• pazopanib

  perphenazine and pazopanib both increase QTc interval. Use Caution/Monitor.
  
  amitriptyline and pazopanib both increase QTc interval. Use Caution/Monitor.

• peginterferon alfa 2b

  peginterferon alfa 2b, perphenazine. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.
  
  peginterferon alfa 2b, amitriptyline. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.

• pentazocine

  amitriptyline and pentazocine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  pentazocine and perphenazine both increase sedation. Use Caution/Monitor.
  
  pentazocine and amitriptyline both increase sedation. Use Caution/Monitor.

• pentobarbital

  pentobarbital and perphenazine both increase sedation. Use Caution/Monitor.
  
  pentobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  pentobarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  pentobarbital and amitriptyline both increase sedation. Use Caution/Monitor.

• perphenazine

  perphenazine and amitriptyline both increase sedation. Use Caution/Monitor.

• phendimetrazine

  perphenazine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine, phendimetrazine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• phendimetrazine

  amitriptyline increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenelzine

  phenelzine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• phenobarbital

  phenobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  phenobarbital and perphenazine both increase sedation. Use Caution/Monitor.
  
  phenobarbital and amitriptyline both increase sedation. Use Caution/Monitor.

• phentermine

  perphenazine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine, phentermine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• phenylephrine

  perphenazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• phenylephrine PO

  perphenazine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .
  
  perphenazine, phenylephrine PO. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• phenylephrine PO

  amitriptyline increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

• phenylephrine ophthalmic

  amitriptyline, phenylephrine ophthalmic. Other (see comment). Use Caution/Monitor. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• phenytoin

  phenytoin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor therapeutic efficacy of amitriptyline; an increased dose may be required. Serum phenytoin levels should be obtained when tricyclic antidepressant agents are added to therapy due to the potential for impaired phenytoin metabolism and decreased seizure threshold. Tricyclic antidepressants when given concomitantly with anticonvulsants can increase CNS depression.
  
  phenytoin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor therapeutic efficacy of amitriptyline; an increased dose may be required. Serum phenytoin levels should be obtained when tricyclic antidepressant agents are added to therapy due to the potential for impaired phenytoin metabolism and decreased seizure threshold. Tricyclic antidepressants when given concomitantly with anticonvulsants can increase CNS depression.

• pholcodine

  perphenazine and pholcodine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and pholcodine both increase sedation. Use Caution/Monitor.

• physostigmine

  physostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• pimozide

  perphenazine and pimozide both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  perphenazine and pimozide both increase sedation. Use Caution/Monitor.

• pilocarpine

  pilocarpine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• pimozide

  pimozide and amitriptyline both increase sedation. Use Caution/Monitor.

• pirbuterol

  amitriptyline increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ponatinib

  ponatinib increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• porfimer

  perphenazine, porfimer. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced photosensitivity.

• posaconazole

  perphenazine and posaconazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  amitriptyline and posaconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• pralidoxime

  perphenazine increases effects of pralidoxime by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  pralidoxime decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  pralidoxime decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  pralidoxime and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• pregabalin

  pregabalin, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• primaquine

  primaquine and perphenazine both increase QTc interval. Use Caution/Monitor.

• primidone

  primidone and perphenazine both increase sedation. Use Caution/Monitor.
  
  primidone will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  primidone and amitriptyline both increase sedation. Use Caution/Monitor.
  
  primidone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• procarbazine

  procarbazine, perphenazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Excessive sedation.
  
  procarbazine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• prochlorperazine

  prochlorperazine and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  prochlorperazine and amitriptyline both increase sedation. Use Caution/Monitor.

• prochlorperazine

  perphenazine and prochlorperazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  perphenazine and prochlorperazine both increase sedation. Use Caution/Monitor.

• promethazine

  promethazine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  promethazine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  perphenazine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  promethazine and perphenazine both increase sedation. Use Caution/Monitor.
  
  promethazine and amitriptyline both increase QTc interval. Use Caution/Monitor.

• propafenone

  perphenazine will increase the level or effect of propafenone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  propafenone will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• propantheline

  propantheline and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• propantheline

  propantheline decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  propantheline decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of propantheline by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• propofol

  propofol and amitriptyline both increase sedation. Use Caution/Monitor.
  
  propofol and perphenazine both increase sedation. Use Caution/Monitor.

• propranolol

  perphenazine will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• propylhexedrine

  amitriptyline increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• propylhexedrine

  perphenazine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine, propylhexedrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• protriptyline

  amitriptyline and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine and protriptyline both increase sedation. Use Caution/Monitor.
  
  amitriptyline and protriptyline both increase sedation. Use Caution/Monitor.

• pseudoephedrine

  perphenazine, pseudoephedrine. Mechanism: unknown. Use Caution/Monitor. Consider avoiding use of pseudoephedrine in patients receiving phenothiazines (especially thioridazine) due to the potential risk of cardiac arrhythmia or sudden death. Monitor for evidence of ventricular arrhythmias during concomitant use.

• pyridostigmine

  pyridostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• quazepam

  quazepam and perphenazine both increase sedation. Use Caution/Monitor.
  
  quazepam and amitriptyline both increase sedation. Use Caution/Monitor.

• quercetin

  quercetin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• quetiapine

  perphenazine and quetiapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  perphenazine and quetiapine both increase sedation. Use Caution/Monitor.

• quetiapine

  quetiapine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  quetiapine, amitriptyline. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Avoid use with drugs that prolong QT and in patients with risk factors for prolonged QT interval. Postmarketing cases show QT prolongation with overdose in patients with concomitant illness or with drugs known to cause electrolyte imbalance or prolong QT.

• quinidine

  quinidine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• quinine

  perphenazine and quinine both increase QTc interval. Use Caution/Monitor.
  
  amitriptyline and quinine both increase QTc interval. Use Caution/Monitor.

• quizartinib

  quizartinib, amitriptyline. Either increases effects of the other by QTc interval. Modify Therapy/Monitor Closely. Monitor patients more frequently with ECG if coadministered with QT prolonging drugs.
  
  quizartinib, perphenazine. Either increases effects of the other by QTc interval. Modify Therapy/Monitor Closely. Monitor patients more frequently with ECG if coadministered with QT prolonging drugs.

• ramelteon

  perphenazine and ramelteon both increase sedation. Use Caution/Monitor.
  
  amitriptyline and ramelteon both increase sedation. Use Caution/Monitor.

• ranolazine

  amitriptyline and ranolazine both increase QTc interval. Modify Therapy/Monitor Closely.
  
  perphenazine and ranolazine both increase QTc interval. Modify Therapy/Monitor Closely.

• rapacuronium

  perphenazine increases effects of rapacuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  rapacuronium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  rapacuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  rapacuronium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• remifentanil

  amitriptyline, remifentanil. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. May also increase risk of serotonin syndrome.

• remimazolam

  remimazolam, perphenazine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

• remimazolam

  remimazolam, amitriptyline. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

• rifabutin

  rifabutin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  rifabutin decreases levels of amitriptyline by increasing metabolism. Use Caution/Monitor.

• rifampin

  rifampin will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  rifampin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  rifampin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• rifapentine

  rifapentine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rilpivirine

  rilpivirine increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

• rimabotulinumtoxinB

  perphenazine, rimabotulinumtoxinB. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Anticholinergics may enhance botulinum toxin effects. Closely monitor for increased neuromuscular blockade.

• risperidone

  amitriptyline and risperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  risperidone and amitriptyline both increase sedation. Use Caution/Monitor.
  
  perphenazine and risperidone both increase sedation. Use Caution/Monitor.
  
  perphenazine and risperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  perphenazine and risperidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

• ritonavir

  ritonavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ritonavir will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• rizatriptan

  rizatriptan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• rivastigmine

  rivastigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• rizatriptan

  rizatriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• rocuronium

  rocuronium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  rocuronium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  perphenazine increases effects of rocuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  rocuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• rolapitant

  rolapitant will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.
  
  rolapitant will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.

• romidepsin

  perphenazine and romidepsin both increase QTc interval. Modify Therapy/Monitor Closely.
  
  amitriptyline and romidepsin both increase QTc interval. Modify Therapy/Monitor Closely.

• salmeterol

  perphenazine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• SAMe

  amitriptyline and SAMe both increase serotonin levels. Modify Therapy/Monitor Closely.

• scopolamine

  scopolamine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  scopolamine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of scopolamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• sarecycline

  sarecycline will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

• scopolamine

  scopolamine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• scullcap

  perphenazine and scullcap both increase sedation. Use Caution/Monitor.
  
  amitriptyline and scullcap both increase sedation. Use Caution/Monitor.

• secobarbital

  secobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  secobarbital and amitriptyline both increase sedation. Use Caution/Monitor.
  
  secobarbital and perphenazine both increase sedation. Use Caution/Monitor.

• selegiline

  selegiline, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• selpercatinib

  selpercatinib increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor.

• selpercatinib

  selpercatinib increases toxicity of perphenazine by QTc interval. Use Caution/Monitor.

• serdexmethylphenidate/dexmethylphenidate

  perphenazine, serdexmethylphenidate/dexmethylphenidate. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• sertraline

  sertraline and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  sertraline and amitriptyline both increase QTc interval. Use Caution/Monitor.

• sevoflurane

  sevoflurane and amitriptyline both increase sedation. Use Caution/Monitor.
  
  sevoflurane and perphenazine both increase sedation. Use Caution/Monitor.
  
  sevoflurane and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  sevoflurane and perphenazine both increase QTc interval. Use Caution/Monitor.

• shepherd's purse

  perphenazine and shepherd's purse both increase sedation. Use Caution/Monitor.
  
  amitriptyline and shepherd's purse both increase sedation. Use Caution/Monitor.

• simvastatin

  simvastatin will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• siponimod

  siponimod and perphenazine both increase QTc interval. Use Caution/Monitor.

• sirolimus

  sirolimus will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• smoking

  smoking decreases levels of perphenazine by increasing metabolism. Use Caution/Monitor. Interaction mainly seen w/chlorpromazine & thioridazine, but may occur w/other phenothiazines.

• sodium sulfate/?magnesium sulfate/potassium chloride

  sodium sulfate/?magnesium sulfate/potassium chloride increases effects of amitriptyline by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of seizures when using higher dose of magnesium sulfate together with drugs that lower the seizure threshold.
  
  sodium sulfate/?magnesium sulfate/potassium chloride increases effects of perphenazine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.

• sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol

  amitriptyline, sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol. Other (see comment). Use Caution/Monitor. Comment: Caution when bowel preps are used with drugs that cause SIADH or NSAIDs; increased risk for water retention or electrolyte imbalance.

• sodium sulfate/potassium sulfate/magnesium sulfate

  sodium sulfate/potassium sulfate/magnesium sulfate increases effects of perphenazine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.

• sodium sulfate/potassium sulfate/magnesium sulfate

  sodium sulfate/potassium sulfate/magnesium sulfate increases effects of amitriptyline by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of seizures when using higher dose of magnesium sulfate together with drugs that lower the seizure threshold.

• solifenacin

  solifenacin and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  solifenacin decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  solifenacin and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  solifenacin and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  solifenacin decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of solifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• sorafenib

  sorafenib and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  sorafenib and perphenazine both increase QTc interval. Use Caution/Monitor.

• St John's Wort

  St John's Wort will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  St John's Wort will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• stiripentol

  stiripentol, perphenazine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

• stiripentol

  stiripentol, amitriptyline. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

• succinylcholine

  succinylcholine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• sufentanil

  sufentanil and amitriptyline both increase sedation. Use Caution/Monitor.
  
  sufentanil and perphenazine both increase sedation. Use Caution/Monitor.

• sufentanil SL

  sufentanil SL, amitriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

• sulfamethoxazole

  perphenazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

• sulfamethoxazole

  amitriptyline and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

• sumatriptan

  sumatriptan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  sumatriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• sumatriptan intranasal

  sumatriptan intranasal, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  sumatriptan intranasal and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• sunitinib

  sunitinib and perphenazine both increase QTc interval. Use Caution/Monitor.

• suvorexant

  suvorexant and amitriptyline both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary

• tacrolimus

  tacrolimus and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  tacrolimus will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• tamoxifen

  perphenazine decreases effects of tamoxifen by decreasing metabolism. Use Caution/Monitor. Inhibition of CYP2D6 metabolism to tamoxifen's active metabolite, endoxifen.

• tapentadol

  tapentadol and amitriptyline both increase sedation. Use Caution/Monitor.
  
  amitriptyline and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• tapentadol

  tapentadol and perphenazine both increase sedation. Use Caution/Monitor.

• telavancin

  perphenazine and telavancin both increase QTc interval. Modify Therapy/Monitor Closely.
  
  amitriptyline and telavancin both increase QTc interval. Modify Therapy/Monitor Closely.

• temazepam

  temazepam and amitriptyline both increase sedation. Use Caution/Monitor.
  
  temazepam and perphenazine both increase sedation. Use Caution/Monitor.

• terbinafine

  terbinafine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.
  
  terbinafine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.

• terbutaline

  perphenazine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• teriflunomide

  teriflunomide decreases levels of amitriptyline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• tetrabenazine

  perphenazine and tetrabenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely.

• tetrabenazine

  tetrabenazine and amitriptyline both increase QTc interval. Use Caution/Monitor.

• thioridazine

  perphenazine and thioridazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  thioridazine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  perphenazine and thioridazine both increase sedation. Use Caution/Monitor.

• thiothixene

  perphenazine and thiothixene both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  perphenazine and thiothixene both increase sedation. Use Caution/Monitor.
  
  thiothixene and amitriptyline both increase sedation. Use Caution/Monitor.

• thyroid desiccated

  thyroid desiccated increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• timolol

  perphenazine will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• tiotropium

  tiotropium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  tiotropium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  tiotropium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  perphenazine increases effects of tiotropium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• tobacco use

  tobacco use decreases levels of perphenazine by increasing metabolism. Use Caution/Monitor. Interaction mainly seen w/chlorpromazine & thioridazine, but may occur w/other phenothiazines.

• tolterodine

  tolterodine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• tolterodine

  tolterodine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  tolterodine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of tolterodine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• tolvaptan

  tolvaptan will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• topiramate

  amitriptyline and topiramate both increase sedation. Modify Therapy/Monitor Closely.
  
  perphenazine and topiramate both increase sedation. Modify Therapy/Monitor Closely.
  
  topiramate increases toxicity of amitriptyline by unspecified interaction mechanism. Use Caution/Monitor. Amitriptyline levels may increase; adjust dose based on clinical response and not on basis of plasma levels.

• tramadol

  tramadol and perphenazine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  tramadol and amitriptyline both increase sedation. Use Caution/Monitor.

• tranylcypromine

  tranylcypromine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• trazodone

  trazodone will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  amitriptyline and trazodone both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  amitriptyline and trazodone both increase sedation. Use Caution/Monitor.

• trazodone

  perphenazine and trazodone both increase sedation. Use Caution/Monitor.

• triazolam

  triazolam and perphenazine both increase sedation. Use Caution/Monitor.
  
  triazolam and amitriptyline both increase sedation. Use Caution/Monitor.

• triclofos

  triclofos and perphenazine both increase sedation. Use Caution/Monitor.
  
  triclofos and amitriptyline both increase sedation. Use Caution/Monitor.

• trifluoperazine

  perphenazine and trifluoperazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  perphenazine and trifluoperazine both increase sedation. Use Caution/Monitor.
  
  trifluoperazine and amitriptyline both increase sedation. Use Caution/Monitor.

• trihexyphenidyl

  trihexyphenidyl decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  trihexyphenidyl and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. Potential for additive anticholinergic effects.
  
  perphenazine increases effects of trihexyphenidyl by pharmacodynamic synergism. Use Caution/Monitor. Potential for additive anticholinergic effects.

• trimethoprim

  perphenazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  amitriptyline and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• trimipramine

  perphenazine and trimipramine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and trimipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  amitriptyline and trimipramine both increase sedation. Use Caution/Monitor.

• triprolidine

  triprolidine and perphenazine both increase sedation. Use Caution/Monitor.
  
  triprolidine and amitriptyline both increase sedation. Use Caution/Monitor.

• tropisetron

  perphenazine and tropisetron both increase QTc interval. Modify Therapy/Monitor Closely.
  
  amitriptyline and tropisetron both increase QTc interval. Modify Therapy/Monitor Closely.

• trospium chloride

  trospium chloride decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  trospium chloride and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine increases effects of trospium chloride by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  trospium chloride decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

• tucatinib

  tucatinib will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

• valbenazine

  valbenazine and perphenazine both increase QTc interval. Use Caution/Monitor.

• valbenazine

  valbenazine and amitriptyline both increase QTc interval. Use Caution/Monitor.

• valerian

  valerian and amitriptyline both increase sedation. Use Caution/Monitor.

• vecuronium

  vecuronium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of vecuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  vecuronium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  vecuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• venlafaxine

  venlafaxine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  amitriptyline and venlafaxine both increase QTc interval. Modify Therapy/Monitor Closely.
  
  venlafaxine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• verapamil

  verapamil will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. The frequency and severity of amitriptyline adverse effects (sedation, anticholinergic effects and orthostatic hypotension) may be increased. Cardiac dysrhythmic effects may be additive.

• vilazodone

  vilazodone, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• voclosporin

  voclosporin, amitriptyline. Either increases effects of the other by QTc interval. Use Caution/Monitor.

• voriconazole

  perphenazine and voriconazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  voriconazole will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  amitriptyline and voriconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• vorinostat

  vorinostat and perphenazine both increase QTc interval. Use Caution/Monitor.

• warfarin

  amitriptyline increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.

• xylometazoline

  perphenazine, xylometazoline. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• yohimbine

  amitriptyline increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine, yohimbine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ziconotide

  amitriptyline and ziconotide both increase sedation. Use Caution/Monitor.
  
  perphenazine and ziconotide both increase sedation. Use Caution/Monitor.

• ziprasidone

  ziprasidone and amitriptyline both increase sedation. Use Caution/Monitor.
  
  perphenazine and ziprasidone both increase sedation. Use Caution/Monitor.
  
  perphenazine and ziprasidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

• zolmitriptan

  zolmitriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  zolmitriptan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• zolpidem

  perphenazine will increase the level or effect of zolpidem by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Additive effect of decreased alertness and psychomotor performance

• zotepine

  perphenazine and zotepine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  perphenazine and zotepine both increase sedation. Use Caution/Monitor.

Minor (164)

• acarbose

  amitriptyline increases effects of acarbose by pharmacodynamic synergism. Minor/Significance Unknown.

• amiodarone

  amiodarone will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• amitriptyline

  amitriptyline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amitriptyline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• amoxapine

  amoxapine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amoxapine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• aripiprazole

  perphenazine will increase the level or effect of aripiprazole by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• armodafinil

  armodafinil will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• artemether/lumefantrine

  artemether/lumefantrine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• asenapine

  asenapine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• atropine

  perphenazine increases toxicity of atropine by unknown mechanism. Minor/Significance Unknown.
  
  amitriptyline increases levels of atropine by unknown mechanism. Minor/Significance Unknown.

• atropine IV/IM

  perphenazine increases toxicity of atropine IV/IM by unknown mechanism. Minor/Significance Unknown.
  
  amitriptyline increases levels of atropine IV/IM by unknown mechanism. Minor/Significance Unknown.

• bazedoxifene/conjugated estrogens

  bazedoxifene/conjugated estrogens, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• benazepril

  perphenazine increases effects of benazepril by unspecified interaction mechanism. Minor/Significance Unknown.

• bortezomib

  bortezomib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• bosentan

  bosentan will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• brimonidine

  amitriptyline decreases effects of brimonidine by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  brimonidine increases effects of perphenazine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

• budesonide

  budesonide will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• captopril

  perphenazine increases effects of captopril by unspecified interaction mechanism. Minor/Significance Unknown.

• butabarbital

  butabarbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• butalbital

  butalbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• carbamazepine

  carbamazepine decreases levels of amitriptyline by increasing metabolism. Minor/Significance Unknown.

• celecoxib

  celecoxib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• chasteberry

  chasteberry decreases effects of perphenazine by pharmacodynamic antagonism. Minor/Significance Unknown. (Theoretical interaction).

• chloroquine

  chloroquine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  chloroquine increases levels of perphenazine by decreasing metabolism. Minor/Significance Unknown.
  
  chloroquine increases toxicity of perphenazine by QTc interval. Minor/Significance Unknown.

• chlorpromazine

  amitriptyline, chlorpromazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amitriptyline, chlorpromazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  perphenazine will increase the level or effect of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• chlorpropamide

  amitriptyline increases effects of chlorpropamide by pharmacodynamic synergism. Minor/Significance Unknown.

• cimetidine

  cimetidine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• clomipramine

  clomipramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  clomipramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• codeine

  perphenazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  perphenazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• conjugated estrogens

  conjugated estrogens, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• conjugated estrogens, vaginal

  conjugated estrogens, vaginal, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• cortisone

  cortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• darifenacin

  darifenacin will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• desflurane

  desflurane, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• desipramine

  desipramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  desipramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• dexamethasone

  dexamethasone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dexfenfluramine

  perphenazine will increase the level or effect of dexfenfluramine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dexmethylphenidate

  dexmethylphenidate increases effects of amitriptyline by decreasing metabolism. Minor/Significance Unknown.

• DHEA, herbal

  DHEA, herbal will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dextroamphetamine

  perphenazine will increase the level or effect of dextroamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dextromethorphan

  perphenazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• diphenhydramine

  diphenhydramine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• donepezil

  perphenazine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• doxepin

  perphenazine will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  doxepin, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  doxepin, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• dronedarone

  dronedarone will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• duloxetine

  duloxetine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• enalapril

  perphenazine increases effects of enalapril by unspecified interaction mechanism. Minor/Significance Unknown.

• encainide

  perphenazine will increase the level or effect of encainide by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• eslicarbazepine acetate

  eslicarbazepine acetate will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• estradiol

  estradiol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• estrogens conjugated synthetic

  estrogens conjugated synthetic, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• estrogens esterified

  estrogens esterified, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens may inhibit hepatic metabolism of tricyclic antidepressants. However, interactions are not common.

• estropipate

  estropipate, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• ethanol

  ethanol, amitriptyline. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive impairment of motor skills.
  
  ethanol, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.

• ethinylestradiol

  ethinylestradiol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• eucalyptus

  perphenazine and eucalyptus both increase sedation. Minor/Significance Unknown.

• etomidate

  etomidate, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• etravirine

  etravirine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• eucalyptus

  amitriptyline and eucalyptus both increase sedation. Minor/Significance Unknown.

• felodipine

  felodipine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• fesoterodine

  perphenazine will increase the level or effect of fesoterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• fludrocortisone

  fludrocortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fluphenazine

  amitriptyline, fluphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amitriptyline, fluphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  perphenazine will increase the level or effect of fluphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• fosinopril

  perphenazine increases effects of fosinopril by unspecified interaction mechanism. Minor/Significance Unknown.

• glimepiride

  amitriptyline increases effects of glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.

• galantamine

  perphenazine will increase the level or effect of galantamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• glipizide

  amitriptyline increases effects of glipizide by pharmacodynamic synergism. Minor/Significance Unknown.

• glyburide

  amitriptyline increases effects of glyburide by pharmacodynamic synergism. Minor/Significance Unknown.

• griseofulvin

  griseofulvin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• haloperidol

  haloperidol will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• hydrocortisone

  hydrocortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• hydroxyprogesterone caproate (DSC)

  hydroxyprogesterone caproate (DSC), amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• imatinib

  imatinib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• imidapril

  perphenazine increases effects of imidapril by unspecified interaction mechanism. Minor/Significance Unknown.

• imipramine

  imipramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  imipramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• insulin aspart

  amitriptyline increases effects of insulin aspart by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin detemir

  amitriptyline increases effects of insulin detemir by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin glargine

  amitriptyline increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin glulisine

  amitriptyline increases effects of insulin glulisine by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin lispro

  amitriptyline increases effects of insulin lispro by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin NPH

  amitriptyline increases effects of insulin NPH by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin regular human

  amitriptyline increases effects of insulin regular human by pharmacodynamic synergism. Minor/Significance Unknown.

• isoniazid

  isoniazid will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• isoproterenol

  isoproterenol, amitriptyline. Mechanism: unknown. Minor/Significance Unknown. Risk of cardiac arrhythmias.

• itraconazole

  itraconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ketamine

  ketamine, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• lapatinib

  lapatinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lisinopril

  perphenazine increases effects of lisinopril by unspecified interaction mechanism. Minor/Significance Unknown.

• lithium

  lithium, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Risk of neurotoxicity in geriatric pts. Multiple mechanisms involved.

• lofepramine

  lofepramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  lofepramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• loratadine

  perphenazine will increase the level or effect of loratadine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• lumefantrine

  lumefantrine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• maprotiline

  maprotiline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  maprotiline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• maraviroc

  maraviroc will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• marijuana

  marijuana will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  marijuana will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• mestranol

  mestranol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• metyrapone

  perphenazine decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown.

• metformin

  amitriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• methylprednisolone

  methylprednisolone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• metronidazole

  metronidazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• metyrapone

  amitriptyline decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown.

• metyrosine

  metyrosine increases toxicity of perphenazine by pharmacodynamic synergism. Minor/Significance Unknown. Increased extrapyramidal symptoms.

• miconazole vaginal

  miconazole vaginal will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• miglitol

  amitriptyline increases effects of miglitol by pharmacodynamic synergism. Minor/Significance Unknown.

• moexipril

  perphenazine increases effects of moexipril by unspecified interaction mechanism. Minor/Significance Unknown.

• nateglinide

  amitriptyline increases effects of nateglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• nevirapine

  nevirapine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nifedipine

  nifedipine will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nilotinib

  nilotinib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  nilotinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nortriptyline

  nortriptyline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  nortriptyline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• oxcarbazepine

  oxcarbazepine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.
  
  oxcarbazepine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• oxybutynin

  oxybutynin increases toxicity of perphenazine by unspecified interaction mechanism. Minor/Significance Unknown.

• oxybutynin topical

  oxybutynin topical increases toxicity of perphenazine by unspecified interaction mechanism. Minor/Significance Unknown.

• oxybutynin transdermal

  oxybutynin transdermal increases toxicity of perphenazine by unspecified interaction mechanism. Minor/Significance Unknown.

• oxycodone

  perphenazine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

• panax ginseng

  panax ginseng increases effects of amitriptyline by pharmacodynamic synergism. Minor/Significance Unknown.

• parecoxib

  parecoxib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  parecoxib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• pentobarbital

  pentobarbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• perhexiline

  perphenazine will increase the level or effect of perhexiline by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• perindopril

  perphenazine increases effects of perindopril by unspecified interaction mechanism. Minor/Significance Unknown.

• perphenazine

  amitriptyline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amitriptyline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• phenobarbital

  phenobarbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• pioglitazone

  amitriptyline increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• pleurisy root

  pleurisy root decreases effects of amitriptyline by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.

• posaconazole

  posaconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• prednisone

  prednisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• primidone

  primidone, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• prochlorperazine

  amitriptyline, prochlorperazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amitriptyline, prochlorperazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  perphenazine will increase the level or effect of prochlorperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• progesterone micronized

  progesterone micronized, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• promazine

  perphenazine will increase the level or effect of promazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• promazine

  amitriptyline, promazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amitriptyline, promazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• promethazine

  perphenazine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  amitriptyline, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amitriptyline, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• propofol

  propofol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• protriptyline

  protriptyline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  protriptyline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• pyrimethamine

  pyrimethamine increases levels of perphenazine by decreasing metabolism. Minor/Significance Unknown.

• quinacrine

  quinacrine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• quinapril

  perphenazine increases effects of quinapril by unspecified interaction mechanism. Minor/Significance Unknown.

• quinupristin/dalfopristin

  quinupristin/dalfopristin will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ramipril

  perphenazine increases effects of ramipril by unspecified interaction mechanism. Minor/Significance Unknown.

• ranolazine

  ranolazine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• repaglinide

  amitriptyline increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• risperidone

  perphenazine will increase the level or effect of risperidone by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• ritonavir

  ritonavir will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• rosiglitazone

  amitriptyline increases effects of rosiglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• rufinamide

  rufinamide will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sage

  perphenazine and sage both increase sedation. Minor/Significance Unknown.
  
  amitriptyline and sage both increase sedation. Minor/Significance Unknown.

• saxagliptin

  amitriptyline increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

• sertraline

  sertraline will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• secobarbital

  secobarbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• serdexmethylphenidate/dexmethylphenidate

  serdexmethylphenidate/dexmethylphenidate increases effects of amitriptyline by decreasing metabolism. Minor/Significance Unknown.

• sevoflurane

  sevoflurane, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• sitagliptin

  amitriptyline increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

• sulfamethoxazole

  sulfamethoxazole decreases levels of amitriptyline by unspecified interaction mechanism. Minor/Significance Unknown.

• thioridazine

  amitriptyline, thioridazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amitriptyline, thioridazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  thioridazine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• tipranavir

  tipranavir will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• tolazamide

  amitriptyline increases effects of tolazamide by pharmacodynamic synergism. Minor/Significance Unknown.

• tolbutamide

  amitriptyline increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

• tolterodine

  perphenazine will increase the level or effect of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• trandolapril

  perphenazine increases effects of trandolapril by unspecified interaction mechanism. Minor/Significance Unknown.

• trazodone

  trazodone, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.
  
  trazodone, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

• trifluoperazine

  perphenazine will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  amitriptyline, trifluoperazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amitriptyline, trifluoperazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• trimipramine

  trimipramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  trimipramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• vasopressin

  amitriptyline increases effects of vasopressin by pharmacodynamic synergism. Minor/Significance Unknown.

• tropisetron

  perphenazine will increase the level or effect of tropisetron by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• verapamil

  verapamil will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  verapamil increases levels of amitriptyline by decreasing metabolism. Minor/Significance Unknown.

• 5-HTP

  Monitor Closely (1)amitriptyline and 5-HTP both increase serotonin levels. Modify Therapy/Monitor Closely.

• abiraterone

  Monitor Closely (2)abiraterone increases levels of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.
  
  abiraterone increases levels of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.

• abobotulinumtoxinA

  Monitor Closely (2)abobotulinumtoxinA increases effects of amitriptyline by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects. .
  
  abobotulinumtoxinA increases effects of perphenazine by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects.

• acarbose

  Minor (1)amitriptyline increases effects of acarbose by pharmacodynamic synergism. Minor/Significance Unknown.

• aclidinium

  Monitor Closely (3)aclidinium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  aclidinium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine increases effects of aclidinium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• acrivastine

  Monitor Closely (2)acrivastine and perphenazine both increase sedation. Use Caution/Monitor.
  
  acrivastine and amitriptyline both increase sedation. Use Caution/Monitor.

• adagrasib

  Serious - Use Alternative (2)adagrasib, amitriptyline. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Each drug prolongs the QTc interval, which may increased the risk of Torsade de pointes, other serious arryhthmias, and sudden death. If coadministration unavoidable, more frequent monitoring is recommended for such patients.
  
  adagrasib, perphenazine. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Each drug prolongs the QTc interval, which may increased the risk of Torsade de pointes, other serious arryhthmias, and sudden death. If coadministration unavoidable, more frequent monitoring is recommended for such patients.

• albiglutide

  Monitor Closely (1)perphenazine, albiglutide. Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase or decrease glucose levels, monitor therapy closely when these agents are concurrently administered.

• albuterol

  Monitor Closely (3)albuterol and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  perphenazine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, albuterol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• alfentanil

  Monitor Closely (2)alfentanil and perphenazine both increase sedation. Use Caution/Monitor.
  
  alfentanil and amitriptyline both increase sedation. Use Caution/Monitor.

• alfuzosin

  Monitor Closely (4)alfuzosin and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  amitriptyline and alfuzosin both increase QTc interval. Use Caution/Monitor.
  
  alfuzosin and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  perphenazine and alfuzosin both increase QTc interval. Use Caution/Monitor.

• almotriptan

  Monitor Closely (2)almotriptan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  almotriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• alprazolam

  Monitor Closely (2)alprazolam and perphenazine both increase sedation. Use Caution/Monitor.
  
  alprazolam and amitriptyline both increase sedation. Use Caution/Monitor.

• amifampridine

  Monitor Closely (2)amitriptyline increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.
  
  perphenazine increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.

• aminolevulinic acid oral

  Serious - Use Alternative (1)aminolevulinic acid oral, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid administering other phototoxic drugs with aminolevulinic acid oral for 24 hr during perioperative period.

• aminolevulinic acid topical

  Serious - Use Alternative (1)perphenazine increases toxicity of aminolevulinic acid topical by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration of photosensitizing drugs may enhance the phototoxic reaction to photodynamic therapy with aminolevulinic acid.

• amiodarone

  Monitor Closely (1)amiodarone will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (2)amitriptyline and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.
  
  perphenazine and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)amiodarone will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• amisulpride

  Contraindicated (1)amisulpride, perphenazine. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Increases risk of neuroleptic malignant syndrome.Monitor Closely (3)amitriptyline and amisulpride both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended if coadministered.
  
  amisulpride and amitriptyline both increase sedation. Use Caution/Monitor.
  
  amisulpride and amitriptyline both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended if coadministered.Serious - Use Alternative (1)perphenazine and amisulpride both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered.

• amitriptyline

  Monitor Closely (1)perphenazine and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)amitriptyline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amitriptyline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• amobarbital

  Monitor Closely (5)amobarbital and amitriptyline both increase sedation. Use Caution/Monitor.
  
  amobarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  amobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  amobarbital and perphenazine both increase sedation. Use Caution/Monitor.
  
  amobarbital, amitriptyline. Other (see comment). Use Caution/Monitor. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• amoxapine

  Monitor Closely (4)amitriptyline and amoxapine both increase sedation. Use Caution/Monitor.
  
  perphenazine and amoxapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely.
  
  perphenazine and amoxapine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and amoxapine both decrease cholinergic effects/transmission. Use Caution/Monitor.Serious - Use Alternative (3)amitriptyline and amoxapine both increase serotonin levels. Avoid or Use Alternate Drug.
  
  perphenazine and amoxapine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and amoxapine both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)amoxapine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amoxapine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• anagrelide

  Monitor Closely (1)anagrelide and perphenazine both increase QTc interval. Use Caution/Monitor.

• anticholinergic/sedative combos

  Monitor Closely (4)anticholinergic/sedative combos and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine increases effects of anticholinergic/sedative combos by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  anticholinergic/sedative combos decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  anticholinergic/sedative combos decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

• apomorphine

  Monitor Closely (3)apomorphine and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  perphenazine and apomorphine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and apomorphine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)apomorphine and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.
  
  perphenazine decreases effects of apomorphine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

• aprepitant

  Monitor Closely (1)aprepitant will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• arformoterol

  Monitor Closely (4)arformoterol and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  arformoterol and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  perphenazine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, arformoterol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• aripiprazole

  Monitor Closely (4)aripiprazole and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  aripiprazole and amitriptyline both increase sedation. Use Caution/Monitor.
  
  aripiprazole and perphenazine both increase sedation. Use Caution/Monitor.
  
  aripiprazole and amitriptyline both increase QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)aripiprazole and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)perphenazine will increase the level or effect of aripiprazole by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• armodafinil

  Monitor Closely (3)perphenazine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  armodafinil will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  amitriptyline increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)armodafinil will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• arsenic trioxide

  Serious - Use Alternative (2)amitriptyline and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.
  
  perphenazine and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.

• artemether

  Monitor Closely (1)artemether and perphenazine both increase QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)artemether and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• artemether/lumefantrine

  Monitor Closely (1)artemether/lumefantrine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (2)perphenazine and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)artemether/lumefantrine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• asenapine

  Monitor Closely (4)asenapine and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  asenapine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  asenapine and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  asenapine and perphenazine both increase sedation. Use Caution/Monitor.Minor (1)asenapine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• asenapine transdermal

  Monitor Closely (4)asenapine transdermal and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  asenapine transdermal and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  asenapine transdermal and amitriptyline both increase sedation. Use Caution/Monitor.
  
  asenapine transdermal and perphenazine both increase sedation. Use Caution/Monitor.

• atazanavir

  Monitor Closely (2)atazanavir increases levels of amitriptyline by unspecified interaction mechanism. Use Caution/Monitor.
  
  atazanavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• atomoxetine

  Monitor Closely (3)perphenazine will increase the level or effect of atomoxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  atomoxetine and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  atomoxetine and perphenazine both increase QTc interval. Use Caution/Monitor.

• atorvastatin

  Monitor Closely (1)atorvastatin will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• atracurium

  Monitor Closely (4)perphenazine increases effects of atracurium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  atracurium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  atracurium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  atracurium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• atropine

  Monitor Closely (4)atropine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  perphenazine increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  atropine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  atropine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.Minor (2)amitriptyline increases levels of atropine by unknown mechanism. Minor/Significance Unknown.
  
  perphenazine increases toxicity of atropine by unknown mechanism. Minor/Significance Unknown.

• atropine IV/IM

  Monitor Closely (4)atropine IV/IM decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  perphenazine increases effects of atropine IV/IM by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  atropine IV/IM decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  atropine IV/IM and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (2)perphenazine increases toxicity of atropine IV/IM by unknown mechanism. Minor/Significance Unknown.
  
  amitriptyline increases levels of atropine IV/IM by unknown mechanism. Minor/Significance Unknown.

• avapritinib

  Monitor Closely (2)avapritinib and amitriptyline both increase sedation. Use Caution/Monitor.
  
  avapritinib and perphenazine both increase sedation. Use Caution/Monitor.

• azelastine

  Monitor Closely (2)azelastine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  azelastine and perphenazine both increase sedation. Use Caution/Monitor.

• azithromycin

  Monitor Closely (2)perphenazine and azithromycin both increase QTc interval. Use Caution/Monitor.
  
  amitriptyline and azithromycin both increase QTc interval. Use Caution/Monitor.

• baclofen

  Monitor Closely (2)baclofen and perphenazine both increase sedation. Use Caution/Monitor.
  
  baclofen and amitriptyline both increase sedation. Use Caution/Monitor.

• bazedoxifene/conjugated estrogens

  Minor (1)bazedoxifene/conjugated estrogens, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• bedaquiline

  Monitor Closely (2)amitriptyline and bedaquiline both increase QTc interval. Modify Therapy/Monitor Closely. ECG should be monitored closely
  
  perphenazine and bedaquiline both increase QTc interval. Modify Therapy/Monitor Closely. ECG should be monitored closely

• belladonna alkaloids

  Monitor Closely (4)perphenazine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  belladonna alkaloids and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.
  
  belladonna alkaloids decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna alkaloids decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

• belladonna and opium

  Monitor Closely (6)belladonna and opium and perphenazine both increase sedation. Use Caution/Monitor.
  
  belladonna and opium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  perphenazine increases effects of belladonna and opium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  belladonna and opium and amitriptyline both increase sedation. Use Caution/Monitor.
  
  belladonna and opium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  belladonna and opium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• benazepril

  Minor (1)perphenazine increases effects of benazepril by unspecified interaction mechanism. Minor/Significance Unknown.

• benperidol

  Monitor Closely (3)benperidol and perphenazine both increase sedation. Use Caution/Monitor.
  
  benperidol and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  benperidol and amitriptyline both increase sedation. Use Caution/Monitor.

• benzhydrocodone/acetaminophen

  Monitor Closely (3)benzhydrocodone/acetaminophen, amitriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.
  
  benzhydrocodone/acetaminophen and perphenazine both increase sedation. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of benzhydrocodone/acetaminophen by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone [benzhydrocodone is prodrug of hydrocodone]) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.Serious - Use Alternative (2)benzhydrocodone/acetaminophen and amitriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate
  
  benzhydrocodone/acetaminophen, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

• benzphetamine

  Monitor Closely (3)perphenazine, benzphetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, benzphetamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• benztropine

  Monitor Closely (2)benztropine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely. Additive anticholinergic adverse effects may be seen with concurrent use.
  
  perphenazine increases effects of benztropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic adverse effects may be seen with concurrent use. .

• bethanechol

  Monitor Closely (1)bethanechol increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• bortezomib

  Minor (1)bortezomib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• bosentan

  Minor (1)bosentan will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• brexanolone

  Monitor Closely (1)brexanolone, perphenazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brexpiprazole

  Monitor Closely (2)brexpiprazole and amitriptyline both increase sedation. Use Caution/Monitor.
  
  brexpiprazole and perphenazine both increase sedation. Use Caution/Monitor.

• brimonidine

  Monitor Closely (2)brimonidine and perphenazine both increase sedation. Use Caution/Monitor.
  
  brimonidine and amitriptyline both increase sedation. Use Caution/Monitor.Minor (2)amitriptyline decreases effects of brimonidine by pharmacodynamic antagonism. Minor/Significance Unknown.
  
  brimonidine increases effects of perphenazine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

• brivaracetam

  Monitor Closely (2)brivaracetam and amitriptyline both increase sedation. Use Caution/Monitor.
  
  brivaracetam and perphenazine both increase sedation. Use Caution/Monitor.

• bromocriptine

  Serious - Use Alternative (1)perphenazine decreases effects of bromocriptine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

• brompheniramine

  Monitor Closely (2)brompheniramine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  brompheniramine and perphenazine both increase sedation. Use Caution/Monitor.

• budesonide

  Minor (1)budesonide will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• buprenorphine

  Monitor Closely (3)buprenorphine and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  buprenorphine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  buprenorphine and perphenazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)buprenorphine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine buccal

  Monitor Closely (3)buprenorphine buccal and amitriptyline both increase sedation. Use Caution/Monitor.
  
  buprenorphine buccal and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  buprenorphine buccal and perphenazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)buprenorphine buccal and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• buprenorphine subdermal implant

  Monitor Closely (3)buprenorphine subdermal implant and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  amitriptyline, buprenorphine subdermal implant. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.
  
  buprenorphine subdermal implant and perphenazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)buprenorphine subdermal implant and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine subdermal implant and amitriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine transdermal

  Monitor Closely (2)buprenorphine transdermal and perphenazine both increase sedation. Use Caution/Monitor.
  
  buprenorphine transdermal and perphenazine both increase QTc interval. Use Caution/Monitor.Serious - Use Alternative (2)buprenorphine transdermal and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine transdermal and amitriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine, long-acting injection

  Monitor Closely (4)buprenorphine, long-acting injection and perphenazine both increase sedation. Use Caution/Monitor.
  
  perphenazine increases toxicity of buprenorphine, long-acting injection by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of buprenorphine and benzodiazepines or other CNS depressants increases risk of adverse reactions including overdose, respiratory depression, and death. Cessation of benzodiazepines or other CNS depressants is preferred in most cases. In some cases, monitoring at a higher level of care for tapering CNS depressants may be appropriate. In others, gradually tapering a patient off of a prescribed benzodiazepine or other CNS depressant or decreasing to the lowest effective dose may be appropriate.
  
  buprenorphine, long-acting injection and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  amitriptyline, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.Serious - Use Alternative (2)buprenorphine, long-acting injection and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine, long-acting injection and amitriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• bupropion

  Monitor Closely (4)bupropion will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  bupropion will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  perphenazine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.
  
  amitriptyline increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

• buspirone

  Serious - Use Alternative (1)amitriptyline and buspirone both increase serotonin levels. Avoid or Use Alternate Drug.

• butabarbital

  Monitor Closely (4)butabarbital and perphenazine both increase sedation. Use Caution/Monitor.
  
  butabarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  butabarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  butabarbital and amitriptyline both increase sedation. Use Caution/Monitor.Minor (1)butabarbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• butalbital

  Monitor Closely (4)butalbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  butalbital and perphenazine both increase sedation. Use Caution/Monitor.
  
  butalbital and amitriptyline both increase sedation. Use Caution/Monitor.Minor (1)butalbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• butorphanol

  Monitor Closely (2)butorphanol and perphenazine both increase sedation. Use Caution/Monitor.
  
  butorphanol and amitriptyline both increase sedation. Use Caution/Monitor.

• cabergoline

  Serious - Use Alternative (1)perphenazine decreases effects of cabergoline by pharmacodynamic antagonism. Contraindicated.

• caffeine

  Monitor Closely (2)perphenazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• calcium/magnesium/potassium/sodium oxybates

  Serious - Use Alternative (2)perphenazine, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  amitriptyline, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• captopril

  Minor (1)perphenazine increases effects of captopril by unspecified interaction mechanism. Minor/Significance Unknown.

• carbachol

  Monitor Closely (1)carbachol increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• carbamazepine

  Monitor Closely (1)carbamazepine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)carbamazepine decreases levels of amitriptyline by increasing metabolism. Minor/Significance Unknown.

• carbinoxamine

  Monitor Closely (2)carbinoxamine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  carbinoxamine and perphenazine both increase sedation. Use Caution/Monitor.

• carisoprodol

  Monitor Closely (2)carisoprodol and amitriptyline both increase sedation. Use Caution/Monitor.
  
  carisoprodol and perphenazine both increase sedation. Use Caution/Monitor.

• carvedilol

  Monitor Closely (1)perphenazine will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• celecoxib

  Minor (1)celecoxib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• cenobamate

  Monitor Closely (2)cenobamate, amitriptyline. Either increases effects of the other by sedation. Use Caution/Monitor.
  
  cenobamate, perphenazine. Either increases effects of the other by sedation. Use Caution/Monitor.

• ceritinib

  Monitor Closely (2)ceritinib and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  ceritinib and amitriptyline both increase QTc interval. Use Caution/Monitor.

• cevimeline

  Monitor Closely (1)cevimeline increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• chasteberry

  Minor (1)chasteberry decreases effects of perphenazine by pharmacodynamic antagonism. Minor/Significance Unknown. (Theoretical interaction).

• chloral hydrate

  Monitor Closely (2)chloral hydrate and perphenazine both increase sedation. Use Caution/Monitor.
  
  chloral hydrate and amitriptyline both increase sedation. Use Caution/Monitor.

• chlordiazepoxide

  Monitor Closely (2)chlordiazepoxide and perphenazine both increase sedation. Use Caution/Monitor.
  
  chlordiazepoxide and amitriptyline both increase sedation. Use Caution/Monitor.

• chloroquine

  Monitor Closely (1)chloroquine increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor.Minor (3)chloroquine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  chloroquine increases levels of perphenazine by decreasing metabolism. Minor/Significance Unknown.
  
  chloroquine increases toxicity of perphenazine by QTc interval. Minor/Significance Unknown.

• chlorpheniramine

  Monitor Closely (2)chlorpheniramine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  chlorpheniramine and perphenazine both increase sedation. Use Caution/Monitor.

• chlorpromazine

  Monitor Closely (3)chlorpromazine and perphenazine both increase sedation. Use Caution/Monitor.
  
  chlorpromazine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  chlorpromazine and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)chlorpromazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  chlorpromazine and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.Minor (3)amitriptyline, chlorpromazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amitriptyline, chlorpromazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  perphenazine will increase the level or effect of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• chlorpropamide

  Minor (1)amitriptyline increases effects of chlorpropamide by pharmacodynamic synergism. Minor/Significance Unknown.

• chlorzoxazone

  Monitor Closely (2)chlorzoxazone and perphenazine both increase sedation. Use Caution/Monitor.
  
  chlorzoxazone and amitriptyline both increase sedation. Use Caution/Monitor.

• cigarette smoking

  Monitor Closely (1)cigarette smoking decreases levels of perphenazine by increasing metabolism. Use Caution/Monitor. Interaction mainly seen w/chlorpromazine & thioridazine, but may occur w/other phenothiazines.

• cimetidine

  Monitor Closely (1)cimetidine will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)cimetidine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• cinnarizine

  Monitor Closely (2)cinnarizine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  cinnarizine and perphenazine both increase sedation. Use Caution/Monitor.

• cisatracurium

  Monitor Closely (4)cisatracurium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  cisatracurium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of cisatracurium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  cisatracurium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• citalopram

  Monitor Closely (1)citalopram and perphenazine both increase QTc interval. Use Caution/Monitor.Serious - Use Alternative (2)citalopram and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  citalopram and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Citalopram may increase TCA levels. Increased risk of serotonin syndrome or neuroleptic malignant syndrome. Potential risk for QT prolongation. ECG monitoring is recommended.

• clarithromycin

  Monitor Closely (1)clarithromycin will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (3)clarithromycin will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  perphenazine and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug.

• clemastine

  Monitor Closely (2)clemastine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  clemastine and perphenazine both increase sedation. Use Caution/Monitor.

• clobazam

  Monitor Closely (3)amitriptyline, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).
  
  clobazam will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly.
  
  clobazam will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly.

• clomipramine

  Monitor Closely (4)amitriptyline and clomipramine both increase sedation. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  amitriptyline and clomipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine and clomipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (3)perphenazine and clomipramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and clomipramine both increase serotonin levels. Avoid or Use Alternate Drug.
  
  amitriptyline and clomipramine both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)clomipramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  clomipramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• clonazepam

  Monitor Closely (2)clonazepam and perphenazine both increase sedation. Use Caution/Monitor.
  
  clonazepam and amitriptyline both increase sedation. Use Caution/Monitor.

• clonidine

  Monitor Closely (1)clonidine, perphenazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.Serious - Use Alternative (1)amitriptyline decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• clorazepate

  Monitor Closely (2)clorazepate and perphenazine both increase sedation. Use Caution/Monitor.
  
  clorazepate and amitriptyline both increase sedation. Use Caution/Monitor.

• clotrimazole

  Monitor Closely (1)clotrimazole will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• clozapine

  Monitor Closely (5)clozapine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  clozapine and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  clozapine and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  clozapine and perphenazine both increase sedation. Use Caution/Monitor.

• cobicistat

  Monitor Closely (3)cobicistat will increase the level or effect of perphenazine by Other (see comment). Modify Therapy/Monitor Closely. A decrease in the dose of antipsychotics that are metabolized by CYP3A or CYP2D6 may be needed upon coadministration.
  
  cobicistat will increase the level or effect of amitriptyline by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.
  
  cobicistat will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Carefully titrate antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant response

• cocaine topical

  Monitor Closely (1)amitriptyline and cocaine topical both increase serotonin levels. Modify Therapy/Monitor Closely.

• codeine

  Monitor Closely (2)codeine and perphenazine both increase sedation. Use Caution/Monitor.
  
  codeine and amitriptyline both increase sedation. Use Caution/Monitor.Minor (2)perphenazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  perphenazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• conivaptan

  Monitor Closely (1)conivaptan will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• conjugated estrogens

  Minor (1)conjugated estrogens, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• conjugated estrogens, vaginal

  Minor (1)conjugated estrogens, vaginal, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• cortisone

  Minor (1)cortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• crizotinib

  Monitor Closely (2)crizotinib and amitriptyline both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.
  
  crizotinib and perphenazine both increase QTc interval. Use Caution/Monitor.

• cyclizine

  Monitor Closely (6)cyclizine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  cyclizine and perphenazine both increase sedation. Use Caution/Monitor.
  
  cyclizine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine increases effects of cyclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  cyclizine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  cyclizine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

• cyclobenzaprine

  Monitor Closely (5)cyclobenzaprine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  cyclobenzaprine and perphenazine both increase sedation. Use Caution/Monitor.
  
  perphenazine increases effects of cyclobenzaprine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  cyclobenzaprine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  cyclobenzaprine and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug.

• cyclosporine

  Monitor Closely (2)cyclosporine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  cyclosporine will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cyproheptadine

  Monitor Closely (2)cyproheptadine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  cyproheptadine and perphenazine both increase sedation. Use Caution/Monitor.

• dacomitinib

  Serious - Use Alternative (2)dacomitinib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.
  
  dacomitinib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

• dantrolene

  Monitor Closely (2)dantrolene and perphenazine both increase sedation. Use Caution/Monitor.
  
  dantrolene and amitriptyline both increase sedation. Use Caution/Monitor.

• daridorexant

  Monitor Closely (2)perphenazine and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
  
  amitriptyline and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• darifenacin

  Monitor Closely (5)darifenacin will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  darifenacin decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  perphenazine increases effects of darifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  darifenacin decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  darifenacin and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.Minor (1)darifenacin will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• darunavir

  Monitor Closely (1)darunavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with SSRIs, TCAs, or trazodone may require dose titration of antidepressant to desired effect (eg, using the lowest feasible initial or maintenance dose). Monitor for antidepressant response.

• dasatinib

  Monitor Closely (2)amitriptyline and dasatinib both increase QTc interval. Modify Therapy/Monitor Closely.
  
  perphenazine and dasatinib both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)dasatinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• debrisoquine

  Monitor Closely (1)amitriptyline decreases effects of debrisoquine by Other (see comment). Use Caution/Monitor. Comment: Inhibition of uptake by adrenergic neurons.

• degarelix

  Monitor Closely (1)degarelix and amitriptyline both increase QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)degarelix and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.

• desflurane

  Monitor Closely (4)desflurane and amitriptyline both increase sedation. Use Caution/Monitor.
  
  desflurane and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  desflurane and perphenazine both increase sedation. Use Caution/Monitor.
  
  desflurane and amitriptyline both increase QTc interval. Use Caution/Monitor.Minor (1)desflurane, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• desipramine

  Monitor Closely (4)amitriptyline and desipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of desipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  perphenazine and desipramine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and desipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (3)perphenazine and desipramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and desipramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and desipramine both increase serotonin levels. Avoid or Use Alternate Drug.Minor (2)desipramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  desipramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• desvenlafaxine

  Monitor Closely (1)desvenlafaxine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mgSerious - Use Alternative (1)amitriptyline and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

• deutetrabenazine

  Monitor Closely (5)perphenazine and deutetrabenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely. The risk for parkinsonism, neuroleptic malignant syndrome, and akathisia may be increased by concomitant use of deutetrabenazine and dopamine antagonists or antipsychotics.
  
  amitriptyline and deutetrabenazine both increase sedation. Use Caution/Monitor.
  
  perphenazine and deutetrabenazine both increase sedation. Use Caution/Monitor.
  
  deutetrabenazine and perphenazine both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).
  
  deutetrabenazine and amitriptyline both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).

• dexamethasone

  Minor (1)dexamethasone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dexchlorpheniramine

  Monitor Closely (2)dexchlorpheniramine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  dexchlorpheniramine and perphenazine both increase sedation. Use Caution/Monitor.

• dexfenfluramine

  Monitor Closely (4)perphenazine, dexfenfluramine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  amitriptyline and dexfenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  perphenazine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, dexfenfluramine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.Minor (1)perphenazine will increase the level or effect of dexfenfluramine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dexmedetomidine

  Monitor Closely (2)dexmedetomidine and perphenazine both increase sedation. Use Caution/Monitor.
  
  dexmedetomidine and amitriptyline both increase sedation. Use Caution/Monitor.

• dexmethylphenidate

  Monitor Closely (3)perphenazine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine, dexmethylphenidate. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.Serious - Use Alternative (1)amitriptyline, dexmethylphenidate. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.Minor (1)dexmethylphenidate increases effects of amitriptyline by decreasing metabolism. Minor/Significance Unknown.

• dextroamphetamine

  Monitor Closely (5)amitriptyline and dextroamphetamine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  amitriptyline increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine, dextroamphetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  amitriptyline increases effects of dextroamphetamine by unknown mechanism. Use Caution/Monitor.
  
  perphenazine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, dextroamphetamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.Minor (1)perphenazine will increase the level or effect of dextroamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dextroamphetamine transdermal

  Monitor Closely (2)amitriptyline will increase the level or effect of dextroamphetamine transdermal by pharmacodynamic synergism. Modify Therapy/Monitor Closely. May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in dextroamphetamine levels in brain; May be potentiate cardiovascular effects. Monitor frequently and adjust or use an alternant based on clinical response.
  
  perphenazine, dextroamphetamine transdermal. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine transdermal and concomitant serotonergic drug(s).

• dextromethorphan

  Monitor Closely (1)dextromethorphan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).Serious - Use Alternative (1)amitriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.Minor (1)perphenazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dextromoramide

  Monitor Closely (2)dextromoramide and perphenazine both increase sedation. Use Caution/Monitor.
  
  dextromoramide and amitriptyline both increase sedation. Use Caution/Monitor.

• DHEA, herbal

  Minor (1)DHEA, herbal will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• diamorphine

  Monitor Closely (2)diamorphine and perphenazine both increase sedation. Use Caution/Monitor.
  
  diamorphine and amitriptyline both increase sedation. Use Caution/Monitor.

• diazepam

  Monitor Closely (2)diazepam and perphenazine both increase sedation. Use Caution/Monitor.
  
  diazepam and amitriptyline both increase sedation. Use Caution/Monitor.

• diazepam intranasal

  Monitor Closely (1)diazepam intranasal, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.

• dicyclomine

  Monitor Closely (4)dicyclomine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  dicyclomine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of dicyclomine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  dicyclomine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• diethylpropion

  Monitor Closely (3)perphenazine, diethylpropion. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, diethylpropion. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• difelikefalin

  Monitor Closely (2)difelikefalin and perphenazine both increase sedation. Use Caution/Monitor.
  
  difelikefalin and amitriptyline both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  Monitor Closely (2)difenoxin hcl and perphenazine both increase sedation. Use Caution/Monitor.
  
  difenoxin hcl and amitriptyline both increase sedation. Use Caution/Monitor.

• dihydroergotamine

  Monitor Closely (2)dihydroergotamine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  amitriptyline and dihydroergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• dihydroergotamine intranasal

  Monitor Closely (1)amitriptyline and dihydroergotamine intranasal both increase serotonin levels. Modify Therapy/Monitor Closely.

• diltiazem

  Monitor Closely (1)diltiazem will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use with amitriptyline may alter blood pressure control.

• dimenhydrinate

  Monitor Closely (2)dimenhydrinate and amitriptyline both increase sedation. Use Caution/Monitor.
  
  dimenhydrinate and perphenazine both increase sedation. Use Caution/Monitor.

• diphenhydramine

  Monitor Closely (6)perphenazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.
  
  diphenhydramine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  diphenhydramine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  diphenhydramine and perphenazine both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• diphenoxylate hcl

  Monitor Closely (2)diphenoxylate hcl and perphenazine both increase sedation. Use Caution/Monitor.
  
  diphenoxylate hcl and amitriptyline both increase sedation. Use Caution/Monitor.

• dipipanone

  Monitor Closely (2)dipipanone and perphenazine both increase sedation. Use Caution/Monitor.
  
  dipipanone and amitriptyline both increase sedation. Use Caution/Monitor.

• disopyramide

  Contraindicated (2)amitriptyline and disopyramide both increase QTc interval. Contraindicated.
  
  perphenazine and disopyramide both increase QTc interval. Contraindicated.

• dobutamine

  Monitor Closely (3)perphenazine, dobutamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, dobutamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• dofetilide

  Monitor Closely (2)dofetilide increases toxicity of perphenazine by QTc interval. Use Caution/Monitor.
  
  dofetilide increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor.Serious - Use Alternative (2)perphenazine and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.

• dolasetron

  Monitor Closely (2)perphenazine and dolasetron both increase QTc interval. Modify Therapy/Monitor Closely.
  
  amitriptyline and dolasetron both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)dolasetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• donepezil

  Monitor Closely (3)donepezil and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  donepezil increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
  
  donepezil and perphenazine both increase QTc interval. Use Caution/Monitor.Minor (1)perphenazine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• donepezil transdermal

  Monitor Closely (1)donepezil transdermal, perphenazine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

• dopamine

  Monitor Closely (3)perphenazine, dopamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (2)perphenazine decreases effects of dopamine by pharmacodynamic antagonism. Contraindicated.
  
  amitriptyline, dopamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• dopexamine

  Monitor Closely (2)perphenazine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, dopexamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• dosulepin

  Monitor Closely (3)amitriptyline and dosulepin both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine and dosulepin both increase sedation. Use Caution/Monitor.
  
  amitriptyline and dosulepin both increase sedation. Use Caution/Monitor.Serious - Use Alternative (3)perphenazine and dosulepin both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and dosulepin both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and dosulepin both increase serotonin levels. Avoid or Use Alternate Drug.

• doxepin

  Monitor Closely (3)perphenazine and doxepin both increase sedation. Use Caution/Monitor.
  
  amitriptyline and doxepin both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  amitriptyline and doxepin both increase sedation. Use Caution/Monitor.Serious - Use Alternative (3)amitriptyline and doxepin both increase serotonin levels. Avoid or Use Alternate Drug.
  
  perphenazine and doxepin both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and doxepin both increase QTc interval. Avoid or Use Alternate Drug.Minor (3)doxepin, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  doxepin, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  perphenazine will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• doxylamine

  Monitor Closely (2)doxylamine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  doxylamine and perphenazine both increase sedation. Use Caution/Monitor.

• dronedarone

  Contraindicated (2)dronedarone will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  dronedarone will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Contraindicated.Serious - Use Alternative (3)dronedarone and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  perphenazine and dronedarone both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and dronedarone both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)dronedarone will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• droperidol

  Monitor Closely (3)droperidol and perphenazine both increase sedation. Use Caution/Monitor.
  
  droperidol and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  droperidol and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)perphenazine and droperidol both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and droperidol both increase QTc interval. Avoid or Use Alternate Drug.

• duloxetine

  Monitor Closely (1)perphenazine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)duloxetine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.Minor (1)duloxetine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• echothiophate iodide

  Monitor Closely (1)echothiophate iodide increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• efavirenz

  Monitor Closely (4)efavirenz and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  efavirenz will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  efavirenz and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  efavirenz will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• elagolix

  Monitor Closely (1)elagolix will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• eletriptan

  Monitor Closely (2)eletriptan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  eletriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• eliglustat

  Monitor Closely (5)eliglustat and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  eliglustat and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  eliglustat increases levels of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the concomitant drug and titrate to clinical effect.
  
  eliglustat increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.
  
  eliglustat increases levels of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the concomitant drug and titrate to clinical effect.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (2)elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; A decrease in dose of the neuroleptic may be needed when coadministered.
  
  elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

• enalapril

  Minor (1)perphenazine increases effects of enalapril by unspecified interaction mechanism. Minor/Significance Unknown.

• encainide

  Minor (1)perphenazine will increase the level or effect of encainide by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• encorafenib

  Monitor Closely (1)encorafenib and perphenazine both increase QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)encorafenib and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• entrectinib

  Monitor Closely (2)entrectinib and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  entrectinib and perphenazine both increase QTc interval. Use Caution/Monitor.

• ephedrine

  Monitor Closely (4)perphenazine, ephedrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases effects of ephedrine by unknown mechanism. Use Caution/Monitor.
  
  amitriptyline increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, ephedrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• epinephrine

  Monitor Closely (5)amitriptyline increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases effects of epinephrine by unknown mechanism. Use Caution/Monitor.
  
  perphenazine decreases effects of epinephrine by pharmacodynamic antagonism. Use Caution/Monitor. Block pressor response to epinephrine, which may result in severe hypotension and tachycardia.
  
  perphenazine, epinephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (3)epinephrine and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.
  
  epinephrine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline, epinephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• epinephrine inhaled

  Monitor Closely (1)amitriptyline and epinephrine inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Tricyclic antidepressants may potentiate epinephrine effect on cardiovascular system.

• epinephrine racemic

  Monitor Closely (4)perphenazine decreases effects of epinephrine racemic by pharmacodynamic antagonism. Use Caution/Monitor. Block pressor response to epinephrine, which may result in severe hypotension and tachycardia.
  
  amitriptyline increases effects of epinephrine racemic by unknown mechanism. Use Caution/Monitor.
  
  perphenazine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (3)epinephrine racemic and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.
  
  epinephrine racemic and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline, epinephrine racemic. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• ergoloid mesylates

  Monitor Closely (1)ergoloid mesylates, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• ergotamine

  Monitor Closely (2)ergotamine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  amitriptyline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• eribulin

  Monitor Closely (2)eribulin and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  eribulin and perphenazine both increase QTc interval. Use Caution/Monitor.

• erythromycin base

  Serious - Use Alternative (4)amitriptyline and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.
  
  erythromycin base will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
  
  erythromycin base will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  perphenazine and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  Serious - Use Alternative (4)erythromycin ethylsuccinate will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
  
  erythromycin ethylsuccinate will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  perphenazine and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  Serious - Use Alternative (4)erythromycin lactobionate will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  erythromycin lactobionate will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
  
  perphenazine and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin stearate

  Serious - Use Alternative (4)erythromycin stearate will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  erythromycin stearate will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
  
  perphenazine and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.

• escitalopram

  Monitor Closely (1)escitalopram increases toxicity of perphenazine by QTc interval. Use Caution/Monitor.Serious - Use Alternative (2)escitalopram and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.
  
  escitalopram increases toxicity of amitriptyline by QTc interval. Avoid or Use Alternate Drug.

• esketamine intranasal

  Monitor Closely (1)esketamine intranasal, amitriptyline. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• eslicarbazepine acetate

  Monitor Closely (1)eslicarbazepine acetate will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.Minor (1)eslicarbazepine acetate will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• esomeprazole

  Monitor Closely (1)esomeprazole will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• estazolam

  Monitor Closely (2)estazolam and amitriptyline both increase sedation. Use Caution/Monitor.
  
  estazolam and perphenazine both increase sedation. Use Caution/Monitor.

• estradiol

  Minor (1)estradiol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• estrogens conjugated synthetic

  Minor (1)estrogens conjugated synthetic, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• estrogens esterified

  Minor (1)estrogens esterified, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens may inhibit hepatic metabolism of tricyclic antidepressants. However, interactions are not common.

• estropipate

  Minor (1)estropipate, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• ethanol

  Monitor Closely (2)perphenazine and ethanol both increase sedation. Use Caution/Monitor.
  
  amitriptyline and ethanol both increase sedation. Use Caution/Monitor.Minor (2)ethanol, amitriptyline. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive impairment of motor skills.
  
  ethanol, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.

• ethinylestradiol

  Minor (1)ethinylestradiol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• etomidate

  Monitor Closely (2)etomidate and amitriptyline both increase sedation. Use Caution/Monitor.
  
  etomidate and perphenazine both increase sedation. Use Caution/Monitor.Minor (1)etomidate, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• etravirine

  Monitor Closely (1)etravirine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.Minor (1)etravirine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• eucalyptus

  Minor (2)amitriptyline and eucalyptus both increase sedation. Minor/Significance Unknown.
  
  perphenazine and eucalyptus both increase sedation. Minor/Significance Unknown.

• ezogabine

  Monitor Closely (1)ezogabine, amitriptyline. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.

• fedratinib

  Monitor Closely (2)fedratinib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.
  
  fedratinib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

• felbamate

  Monitor Closely (1)felbamate will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• felodipine

  Monitor Closely (1)felodipine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)felodipine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• fenfluramine

  Monitor Closely (5)perphenazine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline and fenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  perphenazine, fenfluramine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  fenfluramine, amitriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration with drugs that increase serotoninergic effects may increase the risk of serotonin syndrome.Serious - Use Alternative (1)amitriptyline, fenfluramine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• fentanyl

  Monitor Closely (1)fentanyl, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).Serious - Use Alternative (1)fentanyl, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl intranasal

  Serious - Use Alternative (1)fentanyl intranasal, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl transdermal

  Serious - Use Alternative (1)fentanyl transdermal, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl transmucosal

  Serious - Use Alternative (1)fentanyl transmucosal, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fesoterodine

  Monitor Closely (4)fesoterodine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  perphenazine increases effects of fesoterodine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  fesoterodine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  fesoterodine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.Minor (1)perphenazine will increase the level or effect of fesoterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• fexinidazole

  Serious - Use Alternative (1)fexinidazole and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.

• fezolinetant

  Contraindicated (2)perphenazine will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors
  
  amitriptyline will increase the level or effect of fezolinetant by affecting hepatic enzyme CYP1A2 metabolism. Contraindicated. Fezolinetant AUC and peak plasma concentration are increased if coadministered with drugs that are weak, moderate, or strong CYP1A2 inhibitors

• fingolimod

  Monitor Closely (2)fingolimod and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  fingolimod and amitriptyline both increase QTc interval. Use Caution/Monitor.

• flavoxate

  Monitor Closely (4)perphenazine increases effects of flavoxate by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  flavoxate and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.
  
  flavoxate decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  flavoxate decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

• flecainide

  Monitor Closely (3)amitriptyline and flecainide both increase QTc interval. Modify Therapy/Monitor Closely.
  
  perphenazine will increase the level or effect of flecainide by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  perphenazine and flecainide both increase QTc interval. Modify Therapy/Monitor Closely.

• flibanserin

  Monitor Closely (1)flibanserin, perphenazine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• fluconazole

  Monitor Closely (2)fluconazole will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  fluconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (2)amitriptyline and fluconazole both increase QTc interval. Avoid or Use Alternate Drug.
  
  perphenazine and fluconazole both increase QTc interval. Avoid or Use Alternate Drug.

• fludrocortisone

  Minor (1)fludrocortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fluoxetine

  Monitor Closely (1)amitriptyline and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (5)fluoxetine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug.
  
  perphenazine and fluoxetine both increase QTc interval. Avoid or Use Alternate Drug.
  
  fluoxetine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.
  
  perphenazine will increase the level or effect of fluoxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
  
  fluoxetine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• fluphenazine

  Monitor Closely (3)fluphenazine and perphenazine both increase sedation. Use Caution/Monitor.
  
  fluphenazine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  fluphenazine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.Serious - Use Alternative (2)fluphenazine and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.
  
  fluphenazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (3)amitriptyline, fluphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amitriptyline, fluphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  perphenazine will increase the level or effect of fluphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• flurazepam

  Monitor Closely (2)flurazepam and perphenazine both increase sedation. Use Caution/Monitor.
  
  flurazepam and amitriptyline both increase sedation. Use Caution/Monitor.

• fluvoxamine

  Monitor Closely (2)fluvoxamine and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  fluvoxamine and amitriptyline both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)fluvoxamine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• formoterol

  Monitor Closely (2)perphenazine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (3)amitriptyline, formoterol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.
  
  perphenazine and formoterol both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and formoterol both increase QTc interval. Avoid or Use Alternate Drug.

• fosamprenavir

  Monitor Closely (1)fosamprenavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)fosamprenavir increases levels of amitriptyline by decreasing metabolism. Avoid or Use Alternate Drug.

• fosaprepitant

  Monitor Closely (1)fosaprepitant will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• foscarnet

  Monitor Closely (2)perphenazine and foscarnet both increase QTc interval. Modify Therapy/Monitor Closely.
  
  amitriptyline and foscarnet both increase QTc interval. Modify Therapy/Monitor Closely.

• fosinopril

  Minor (1)perphenazine increases effects of fosinopril by unspecified interaction mechanism. Minor/Significance Unknown.

• fosphenytoin

  Monitor Closely (2)fosphenytoin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  fosphenytoin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fostemsavir

  Monitor Closely (1)amitriptyline and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

• frovatriptan

  Monitor Closely (2)frovatriptan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  frovatriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• gabapentin

  Monitor Closely (1)gabapentin, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• gabapentin enacarbil

  Monitor Closely (1)gabapentin enacarbil, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• galantamine

  Monitor Closely (1)galantamine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.Minor (1)perphenazine will increase the level or effect of galantamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• ganaxolone

  Monitor Closely (2)amitriptyline and ganaxolone both increase sedation. Use Caution/Monitor.
  
  perphenazine and ganaxolone both increase sedation. Use Caution/Monitor.

• gemifloxacin

  Monitor Closely (2)gemifloxacin and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  gemifloxacin and perphenazine both increase QTc interval. Use Caution/Monitor.

• gilteritinib

  Monitor Closely (2)gilteritinib and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  gilteritinib and perphenazine both increase QTc interval. Use Caution/Monitor.

• givosiran

  Serious - Use Alternative (2)givosiran will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.
  
  givosiran will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.

• glecaprevir/pibrentasvir

  Monitor Closely (1)glecaprevir/pibrentasvir will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

• glimepiride

  Minor (1)amitriptyline increases effects of glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.

• glipizide

  Minor (1)amitriptyline increases effects of glipizide by pharmacodynamic synergism. Minor/Significance Unknown.

• glyburide

  Minor (1)amitriptyline increases effects of glyburide by pharmacodynamic synergism. Minor/Significance Unknown.

• glycopyrrolate

  Monitor Closely (4)perphenazine increases effects of glycopyrrolate by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  amitriptyline increases levels of glycopyrrolate by unknown mechanism. Use Caution/Monitor.
  
  perphenazine increases toxicity of glycopyrrolate by unknown mechanism. Use Caution/Monitor.
  
  glycopyrrolate and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• glycopyrrolate inhaled

  Monitor Closely (6)perphenazine increases toxicity of glycopyrrolate inhaled by unknown mechanism. Use Caution/Monitor.
  
  glycopyrrolate inhaled decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of glycopyrrolate inhaled by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  glycopyrrolate inhaled decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  amitriptyline increases levels of glycopyrrolate inhaled by unknown mechanism. Use Caution/Monitor.
  
  glycopyrrolate inhaled and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• glycopyrronium tosylate topical

  Monitor Closely (2)glycopyrronium tosylate topical, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of glycopyrronium tosylate topical with other anticholinergic medications may result in additive anticholinergic adverse effects.
  
  glycopyrronium tosylate topical, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of glycopyrronium tosylate topical with other anticholinergic medications may result in additive anticholinergic adverse effects.

• granisetron

  Monitor Closely (1)granisetron and perphenazine both increase QTc interval. Use Caution/Monitor.Serious - Use Alternative (2)granisetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.
  
  granisetron and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• grapefruit

  Monitor Closely (1)grapefruit will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• griseofulvin

  Minor (1)griseofulvin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• guanfacine

  Monitor Closely (1)guanfacine, perphenazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.Serious - Use Alternative (1)amitriptyline decreases effects of guanfacine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• haloperidol

  Monitor Closely (4)haloperidol and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  haloperidol and amitriptyline both increase sedation. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of haloperidol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  haloperidol and perphenazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)amitriptyline and haloperidol both increase QTc interval. Avoid or Use Alternate Drug.
  
  perphenazine and haloperidol both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)haloperidol will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• henbane

  Monitor Closely (4)henbane decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  henbane decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  henbane and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine increases effects of henbane by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• homatropine

  Monitor Closely (4)homatropine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  homatropine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of homatropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  homatropine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• huperzine A

  Monitor Closely (1)huperzine A increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• hydrocodone

  Monitor Closely (2)hydrocodone, amitriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.
  
  perphenazine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.Serious - Use Alternative (1)hydrocodone, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

• hydrocortisone

  Minor (1)hydrocortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• hydromorphone

  Monitor Closely (3)perphenazine will increase the level or effect of hydromorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  hydromorphone and perphenazine both increase sedation. Use Caution/Monitor.
  
  hydromorphone and amitriptyline both increase sedation. Use Caution/Monitor.

• hydroxychloroquine sulfate

  Serious - Use Alternative (2)hydroxychloroquine sulfate and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  hydroxychloroquine sulfate and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.

• hydroxyprogesterone caproate (DSC)

  Minor (1)hydroxyprogesterone caproate (DSC), amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• hydroxyzine

  Monitor Closely (4)hydroxyzine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  hydroxyzine and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  hydroxyzine and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  hydroxyzine and perphenazine both increase sedation. Use Caution/Monitor.

• hyoscyamine

  Monitor Closely (4)hyoscyamine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  hyoscyamine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  hyoscyamine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of hyoscyamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• hyoscyamine spray

  Monitor Closely (4)perphenazine increases effects of hyoscyamine spray by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  hyoscyamine spray and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  hyoscyamine spray decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  hyoscyamine spray decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• ibutilide

  Contraindicated (2)perphenazine and ibutilide both increase QTc interval. Contraindicated.
  
  amitriptyline and ibutilide both increase QTc interval. Contraindicated.

• iloperidone

  Monitor Closely (6)perphenazine and iloperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  iloperidone and perphenazine both increase sedation. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of iloperidone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  amitriptyline and iloperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  iloperidone and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  iloperidone and amitriptyline both increase sedation. Use Caution/Monitor.

• imatinib

  Minor (1)imatinib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• imidapril

  Minor (1)perphenazine increases effects of imidapril by unspecified interaction mechanism. Minor/Significance Unknown.

• imipramine

  Monitor Closely (4)amitriptyline and imipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine and imipramine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and imipramine both increase sedation. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (3)amitriptyline and imipramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  perphenazine and imipramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and imipramine both increase serotonin levels. Avoid or Use Alternate Drug.Minor (2)imipramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  imipramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• incobotulinumtoxinA

  Monitor Closely (1)perphenazine, incobotulinumtoxinA. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects.

• indacaterol, inhaled

  Monitor Closely (2)indacaterol, inhaled, amitriptyline. QTc interval. Use Caution/Monitor. Indacaterol should be administered with extreme caution to patients treated with TCAs. Drugs that are known to prolong the QTc interval may have an increased the risk of ventricular arrhythmias.
  
  indacaterol, inhaled, perphenazine. QTc interval. Use Caution/Monitor. Drugs that are known to prolong the QTc interval may have an increased the risk of ventricular arrhythmias.

• indapamide

  Contraindicated (2)perphenazine and indapamide both increase QTc interval. Contraindicated.
  
  amitriptyline and indapamide both increase QTc interval. Contraindicated.

• indinavir

  Monitor Closely (1)indinavir will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• insulin aspart

  Minor (1)amitriptyline increases effects of insulin aspart by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin degludec

  Monitor Closely (1)perphenazine decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

• insulin degludec/insulin aspart

  Monitor Closely (1)perphenazine decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

• insulin detemir

  Minor (1)amitriptyline increases effects of insulin detemir by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin glargine

  Minor (1)amitriptyline increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin glulisine

  Minor (1)amitriptyline increases effects of insulin glulisine by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin inhaled

  Monitor Closely (1)perphenazine decreases effects of insulin inhaled by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

• insulin lispro

  Minor (1)amitriptyline increases effects of insulin lispro by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin NPH

  Minor (1)amitriptyline increases effects of insulin NPH by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin regular human

  Minor (1)amitriptyline increases effects of insulin regular human by pharmacodynamic synergism. Minor/Significance Unknown.

• iobenguane I 123

  Contraindicated (1)amitriptyline decreases effects of iobenguane I 123 by pharmacodynamic antagonism. Contraindicated. If clinically appropriate, discontinue drugs that decrease uptake of NE for at least 5 half-lives; may cause false-negative imaging results.

• iobenguane I 131

  Serious - Use Alternative (1)amitriptyline will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.

• ipratropium

  Monitor Closely (4)ipratropium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. Due to the poor systemic absorption of ipratropium, interaction unlikely at regularly recommended dosages.
  
  ipratropium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  ipratropium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of ipratropium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• isocarboxazid

  Contraindicated (1)isocarboxazid and amitriptyline both increase serotonin levels. Contraindicated.Serious - Use Alternative (1)isocarboxazid, perphenazine. Other (see comment). Contraindicated. Comment: Concurrent use may prolong or intensify the hypotensive, anticholinergic, or sedative effects of isocarboxazid or perphenazine.

• isoflurane

  Monitor Closely (2)isoflurane and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  isoflurane and perphenazine both increase QTc interval. Use Caution/Monitor.

• isoniazid

  Monitor Closely (2)amitriptyline and isoniazid both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  isoniazid will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.Minor (1)isoniazid will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• isoproterenol

  Monitor Closely (3)perphenazine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine, isoproterenol. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.Serious - Use Alternative (1)amitriptyline, isoproterenol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.Minor (1)isoproterenol, amitriptyline. Mechanism: unknown. Minor/Significance Unknown. Risk of cardiac arrhythmias.

• istradefylline

  Monitor Closely (1)istradefylline will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

• itraconazole

  Monitor Closely (2)itraconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  itraconazole and amitriptyline both increase QTc interval. Use Caution/Monitor.Minor (1)itraconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)perphenazine and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

• ivacaftor

  Monitor Closely (1)ivacaftor increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

• ivosidenib

  Serious - Use Alternative (2)ivosidenib and perphenazine both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of QTc prolonging drugs with ivosidenib or replace with alternate therapies. If coadministration of a QTc prolonging drug is unavoidable, monitor for increased risk of QTc interval prolongation.
  
  ivosidenib and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of QTc prolonging drugs with ivosidenib or replace with alternate therapies. If coadministration of a QTc prolonging drug is unavoidable, monitor for increased risk of QTc interval prolongation.

• ketamine

  Monitor Closely (2)ketamine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  ketamine and perphenazine both increase sedation. Use Caution/Monitor.Minor (1)ketamine, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• ketoconazole

  Monitor Closely (2)ketoconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (2)perphenazine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• ketotifen, ophthalmic

  Monitor Closely (2)perphenazine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.
  
  amitriptyline and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

• L-tryptophan

  Monitor Closely (1)amitriptyline and L-tryptophan both increase serotonin levels. Modify Therapy/Monitor Closely.

• lapatinib

  Monitor Closely (2)amitriptyline and lapatinib both increase QTc interval. Modify Therapy/Monitor Closely.
  
  perphenazine and lapatinib both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)lapatinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lasmiditan

  Monitor Closely (3)lasmiditan, amitriptyline. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.
  
  lasmiditan, perphenazine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.
  
  amitriptyline increases effects of lasmiditan by serotonin levels. Use Caution/Monitor. Coadministration may increase risk of serotonin syndrome.Serious - Use Alternative (1)lasmiditan increases effects of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• lefamulin

  Serious - Use Alternative (1)lefamulin and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• lemborexant

  Monitor Closely (2)lemborexant, perphenazine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.
  
  lemborexant, amitriptyline. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

• letermovir

  Monitor Closely (1)letermovir increases levels of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levalbuterol

  Monitor Closely (2)perphenazine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, levalbuterol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• levodopa

  Serious - Use Alternative (1)perphenazine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

• levodopa inhaled

  Serious - Use Alternative (1)perphenazine decreases effects of levodopa inhaled by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Phenothiazine/1st generation antipsychotics inhibit dopamine D2 receptors in varying degrees.

• levofloxacin

  Monitor Closely (2)amitriptyline and levofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.
  
  perphenazine and levofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

• levoketoconazole

  Monitor Closely (2)levoketoconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  levoketoconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (2)perphenazine and levoketoconazole both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and levoketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• levomilnacipran

  Monitor Closely (1)levomilnacipran, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).Serious - Use Alternative (1)levomilnacipran and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• levorphanol

  Monitor Closely (2)levorphanol and amitriptyline both increase sedation. Use Caution/Monitor.
  
  levorphanol and perphenazine both increase sedation. Use Caution/Monitor.

• levothyroxine

  Monitor Closely (1)levothyroxine increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• linezolid

  Monitor Closely (1)linezolid, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).Serious - Use Alternative (1)linezolid and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.

• liothyronine

  Monitor Closely (1)liothyronine increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• liotrix

  Monitor Closely (1)liotrix increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• liraglutide

  Monitor Closely (1)perphenazine, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase or decrease glucose levels, monitor therapy closely when these agents are concurrently administered.

• lisdexamfetamine

  Monitor Closely (4)amitriptyline increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline, lisdexamfetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue along with concomitant serotonergic drug(s).
  
  perphenazine, lisdexamfetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, lisdexamfetamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• lisinopril

  Minor (1)perphenazine increases effects of lisinopril by unspecified interaction mechanism. Minor/Significance Unknown.

• lisuride

  Serious - Use Alternative (1)perphenazine decreases effects of lisuride by pharmacodynamic antagonism. Contraindicated.

• lithium

  Monitor Closely (5)lithium and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  lithium and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  lithium, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  amitriptyline and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  lithium, perphenazine. Other (see comment). Use Caution/Monitor. Comment: Risk of neurotoxicity. Multiple mechanisms involved.Minor (1)lithium, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Risk of neurotoxicity in geriatric pts. Multiple mechanisms involved.

• lofepramine

  Monitor Closely (4)perphenazine and lofepramine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and lofepramine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and lofepramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of lofepramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (3)amitriptyline and lofepramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and lofepramine both increase serotonin levels. Avoid or Use Alternate Drug.
  
  perphenazine and lofepramine both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)lofepramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  lofepramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• lofexidine

  Monitor Closely (3)perphenazine and lofexidine both increase sedation. Use Caution/Monitor.
  
  amitriptyline decreases effects of lofexidine by unspecified interaction mechanism. Use Caution/Monitor.
  
  amitriptyline and lofexidine both increase sedation. Use Caution/Monitor.

• loprazolam

  Monitor Closely (2)loprazolam and amitriptyline both increase sedation. Use Caution/Monitor.
  
  loprazolam and perphenazine both increase sedation. Use Caution/Monitor.

• loratadine

  Monitor Closely (1)loratadine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)perphenazine will increase the level or effect of loratadine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• lorazepam

  Monitor Closely (2)lorazepam and perphenazine both increase sedation. Use Caution/Monitor.
  
  lorazepam and amitriptyline both increase sedation. Use Caution/Monitor.

• lorcaserin

  Monitor Closely (3)lorcaserin will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  lorcaserin will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  lorcaserin, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).Serious - Use Alternative (2)amitriptyline and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.
  
  perphenazine and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.

• lormetazepam

  Monitor Closely (2)lormetazepam and perphenazine both increase sedation. Use Caution/Monitor.
  
  lormetazepam and amitriptyline both increase sedation. Use Caution/Monitor.

• loxapine

  Monitor Closely (3)loxapine and perphenazine both increase sedation. Use Caution/Monitor.
  
  loxapine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  loxapine and amitriptyline both increase sedation. Use Caution/Monitor.

• loxapine inhaled

  Monitor Closely (3)loxapine inhaled and perphenazine both increase sedation. Use Caution/Monitor.
  
  loxapine inhaled and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  loxapine inhaled and amitriptyline both increase sedation. Use Caution/Monitor.

• lsd

  Monitor Closely (1)amitriptyline and lsd both increase serotonin levels. Modify Therapy/Monitor Closely.

• lumefantrine

  Monitor Closely (1)lumefantrine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (2)perphenazine and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)lumefantrine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lurasidone

  Monitor Closely (3)lurasidone, amitriptyline. Either increases toxicity of the other by sedation. Use Caution/Monitor. Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.
  
  lurasidone, perphenazine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.
  
  lurasidone increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of hypotension with concurrent use. Monitor blood pressure and adjust dose of antihypertensive agent as needed.

• macimorelin

  Serious - Use Alternative (2)macimorelin and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug. Macimorelin causes an increase of ~11 msec in the corrected QT interval. Avoid coadministration with drugs that prolong QT interval, which could increase risk for developing torsade de pointes-type ventricular tachycardia. Allow sufficient washout time of drugs that are known to prolong the QT interval before administering macimorelin.
  
  macimorelin and perphenazine both increase QTc interval. Avoid or Use Alternate Drug. Macimorelin causes an increase of ~11 msec in the corrected QT interval. Avoid coadministration with drugs that prolong QT interval, which could increase risk for developing torsade de pointes-type ventricular tachycardia. Allow sufficient washout time of drugs that are known to prolong the QT interval before administering macimorelin.

• maprotiline

  Monitor Closely (3)perphenazine and maprotiline both increase sedation. Use Caution/Monitor.
  
  amitriptyline and maprotiline both increase sedation. Use Caution/Monitor.
  
  amitriptyline and maprotiline both decrease cholinergic effects/transmission. Use Caution/Monitor.Serious - Use Alternative (3)amitriptyline and maprotiline both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and maprotiline both increase serotonin levels. Avoid or Use Alternate Drug.
  
  perphenazine and maprotiline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)maprotiline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  maprotiline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• maraviroc

  Monitor Closely (1)maraviroc, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.Minor (1)maraviroc will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• marijuana

  Monitor Closely (2)perphenazine and marijuana both increase sedation. Use Caution/Monitor.
  
  amitriptyline and marijuana both increase sedation. Use Caution/Monitor.Minor (2)marijuana will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  marijuana will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• mavacamten

  Monitor Closely (1)amitriptyline will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

• meclizine

  Monitor Closely (4)meclizine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  meclizine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of meclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  meclizine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• mefloquine

  Serious - Use Alternative (1)mefloquine increases toxicity of amitriptyline by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.

• melatonin

  Monitor Closely (2)perphenazine and melatonin both increase sedation. Use Caution/Monitor.
  
  amitriptyline and melatonin both increase sedation. Use Caution/Monitor.

• meperidine

  Monitor Closely (3)meperidine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  meperidine and perphenazine both increase sedation. Use Caution/Monitor.
  
  meperidine and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline and meperidine both increase serotonin levels. Avoid or Use Alternate Drug.

• meprobamate

  Monitor Closely (2)amitriptyline and meprobamate both increase sedation. Use Caution/Monitor.
  
  perphenazine and meprobamate both increase sedation. Use Caution/Monitor.

• mestranol

  Minor (1)mestranol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• metaproterenol

  Monitor Closely (2)perphenazine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, metaproterenol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• metaxalone

  Monitor Closely (2)metaxalone and amitriptyline both increase sedation. Use Caution/Monitor.
  
  metaxalone and perphenazine both increase sedation. Use Caution/Monitor.

• metformin

  Monitor Closely (1)perphenazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.Minor (1)amitriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• methadone

  Monitor Closely (5)perphenazine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  methadone, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  methadone and perphenazine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and methadone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  methadone and amitriptyline both increase sedation. Use Caution/Monitor.

• methamphetamine

  Monitor Closely (4)perphenazine, methamphetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, methamphetamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• methocarbamol

  Monitor Closely (2)methocarbamol and perphenazine both increase sedation. Use Caution/Monitor.
  
  methocarbamol and amitriptyline both increase sedation. Use Caution/Monitor.

• methoxsalen

  Monitor Closely (1)methoxsalen, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive photosensitizing effects.

• methscopolamine

  Monitor Closely (4)methscopolamine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine increases effects of methscopolamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  methscopolamine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  methscopolamine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

• methyl aminolevulinate

  Serious - Use Alternative (1)perphenazine, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

• methyldopa

  Serious - Use Alternative (1)perphenazine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

• methylene blue

  Serious - Use Alternative (1)methylene blue and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.

• methylenedioxymethamphetamine

  Monitor Closely (3)perphenazine, methylenedioxymethamphetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, methylenedioxymethamphetamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• methylergonovine

  Monitor Closely (1)methylergonovine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• methylphenidate

  Monitor Closely (3)amitriptyline, methylphenidate. Other (see comment). Use Caution/Monitor. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.
  
  perphenazine, methylphenidate. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases toxicity of methylphenidate by pharmacodynamic antagonism. Use Caution/Monitor. Closely monitor for signs of altered clinical response to either methylphenidate or an antipsychotic when using these drugs in combination.

• methylphenidate transdermal

  Monitor Closely (1)methylphenidate transdermal will increase the level or effect of amitriptyline by decreasing elimination. Modify Therapy/Monitor Closely. Consider decreasing the dose of these drugs when given coadministered with methylphenidate. Monitor for drug toxiticities when initiating or discontinuing methylphenidate.

• methylprednisolone

  Minor (1)methylprednisolone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• metoclopramide

  Monitor Closely (1)perphenazine and metoclopramide both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

• metoclopramide intranasal

  Serious - Use Alternative (3)perphenazine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.
  
  perphenazine increases toxicity of metoclopramide intranasal by pharmacodynamic synergism. Avoid or Use Alternate Drug. Potential for additive effects, including increased frequency and severity of tardive dyskinesia, other extrapyramidal symptoms, and neuroleptic malignant syndrome.
  
  amitriptyline, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

• metoprolol

  Monitor Closely (1)perphenazine will increase the level or effect of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• metrizamide

  Contraindicated (1)perphenazine, metrizamide. Mechanism: unknown. Contraindicated. Risk of seizure. D/C phenothiazine 24h before admin. of metrizamide.

• metronidazole

  Minor (1)metronidazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• metyrapone

  Minor (2)amitriptyline decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown.
  
  perphenazine decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown.

• metyrosine

  Minor (1)metyrosine increases toxicity of perphenazine by pharmacodynamic synergism. Minor/Significance Unknown. Increased extrapyramidal symptoms.

• mexiletine

  Monitor Closely (1)perphenazine will increase the level or effect of mexiletine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• miconazole vaginal

  Minor (1)miconazole vaginal will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• midazolam

  Monitor Closely (2)midazolam and perphenazine both increase sedation. Use Caution/Monitor.
  
  midazolam and amitriptyline both increase sedation. Use Caution/Monitor.

• midazolam intranasal

  Monitor Closely (2)midazolam intranasal, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.
  
  midazolam intranasal, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

• midodrine

  Monitor Closely (3)perphenazine, midodrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, midodrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• mifepristone

  Monitor Closely (2)mifepristone, perphenazine. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.
  
  mifepristone, amitriptyline. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.

• miglitol

  Minor (1)amitriptyline increases effects of miglitol by pharmacodynamic synergism. Minor/Significance Unknown.

• milnacipran

  Monitor Closely (1)milnacipran, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).Serious - Use Alternative (1)milnacipran and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• mipomersen

  Monitor Closely (1)mipomersen, amitriptyline. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

• mirabegron

  Monitor Closely (2)mirabegron will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  mirabegron will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• mirtazapine

  Monitor Closely (4)perphenazine and mirtazapine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  amitriptyline and mirtazapine both increase sedation. Use Caution/Monitor.
  
  mirtazapine and perphenazine both increase QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)mirtazapine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• mobocertinib

  Serious - Use Alternative (2)mobocertinib will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently
  
  mobocertinib and perphenazine both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.

• modafinil

  Monitor Closely (3)perphenazine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  modafinil will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• moexipril

  Minor (1)perphenazine increases effects of moexipril by unspecified interaction mechanism. Minor/Significance Unknown.

• morphine

  Monitor Closely (4)perphenazine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  amitriptyline and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  morphine and perphenazine both increase sedation. Use Caution/Monitor.
  
  morphine and amitriptyline both increase sedation. Use Caution/Monitor.

• motherwort

  Monitor Closely (2)perphenazine and motherwort both increase sedation. Use Caution/Monitor.
  
  amitriptyline and motherwort both increase sedation. Use Caution/Monitor.

• moxifloxacin

  Serious - Use Alternative (2)perphenazine and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• moxonidine

  Monitor Closely (2)perphenazine and moxonidine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and moxonidine both increase sedation. Use Caution/Monitor.

• nabilone

  Monitor Closely (2)perphenazine and nabilone both increase sedation. Use Caution/Monitor.
  
  amitriptyline and nabilone both increase sedation. Use Caution/Monitor.

• nalbuphine

  Monitor Closely (2)nalbuphine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  nalbuphine and perphenazine both increase sedation. Use Caution/Monitor.

• naratriptan

  Monitor Closely (2)naratriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  naratriptan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• nateglinide

  Minor (1)amitriptyline increases effects of nateglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• nebivolol

  Monitor Closely (1)perphenazine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• nefazodone

  Monitor Closely (2)nefazodone will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  nefazodone will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)nefazodone and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• nefopam

  Monitor Closely (1)nefopam, amitriptyline. Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Use combination with caution.

• nelfinavir

  Monitor Closely (1)nelfinavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• neostigmine

  Monitor Closely (1)neostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• netupitant/palonosetron

  Serious - Use Alternative (1)netupitant/palonosetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• nevirapine

  Minor (1)nevirapine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nicardipine

  Monitor Closely (1)nicardipine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• nifedipine

  Monitor Closely (1)nifedipine will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)nifedipine will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nilotinib

  Serious - Use Alternative (2)perphenazine and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)nilotinib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  nilotinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• norepinephrine

  Monitor Closely (4)amitriptyline increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine, norepinephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases effects of norepinephrine by unknown mechanism. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, norepinephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• nortriptyline

  Monitor Closely (4)amitriptyline and nortriptyline both increase sedation. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  amitriptyline and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine and nortriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (3)perphenazine and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.
  
  amitriptyline and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)nortriptyline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  nortriptyline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• octreotide

  Serious - Use Alternative (2)perphenazine and octreotide both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and octreotide both increase QTc interval. Avoid or Use Alternate Drug.

• octreotide (Antidote)

  Serious - Use Alternative (2)amitriptyline and octreotide (Antidote) both increase QTc interval. Avoid or Use Alternate Drug.
  
  perphenazine and octreotide (Antidote) both increase QTc interval. Avoid or Use Alternate Drug.

• ofloxacin

  Monitor Closely (2)amitriptyline and ofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.
  
  perphenazine and ofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

• olanzapine

  Monitor Closely (5)olanzapine and perphenazine both increase sedation. Use Caution/Monitor.
  
  olanzapine and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  olanzapine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  olanzapine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  olanzapine and perphenazine both increase QTc interval. Use Caution/Monitor.

• oliceridine

  Monitor Closely (3)amitriptyline, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely.
  
  oliceridine, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).
  
  amitriptyline increases toxicity of oliceridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor for signs of urinary retention or reduced gastric motility if oliceridine is coadministered with anticholinergics.

• olodaterol inhaled

  Monitor Closely (2)amitriptyline and olodaterol inhaled both increase QTc interval. Use Caution/Monitor. TCAs prolong the QTc interval and may potentiate the effects of beta2 agonists on the cardiovascular system; increased risk of ventricular arrhythmias
  
  perphenazine and olodaterol inhaled both increase QTc interval. Use Caution/Monitor. Drugs that prolong the QTc interval and may potentiate the effects of beta2 agonists on the cardiovascular system; increased risk of ventricular arrhythmias

• olopatadine intranasal

  Serious - Use Alternative (2)perphenazine and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.
  
  amitriptyline and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• onabotulinumtoxinA

  Monitor Closely (4)onabotulinumtoxinA and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.
  
  onabotulinumtoxinA decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  onabotulinumtoxinA decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of onabotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• ondansetron

  Serious - Use Alternative (3)perphenazine and ondansetron both increase QTc interval. Avoid or Use Alternate Drug. Avoid with congenital long QT syndrome; ECG monitoring recommended with concomitant medications that prolong QT interval, electrolyte abnormalities, CHF, or bradyarrhythmias.
  
  amitriptyline and ondansetron both increase QTc interval. Avoid or Use Alternate Drug. Avoid with congenital long QT syndrome; ECG monitoring recommended with concomitant medications that prolong QT interval, electrolyte abnormalities, CHF, or bradyarrhythmias.
  
  ondansetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• opium tincture

  Monitor Closely (2)opium tincture and perphenazine both increase sedation. Use Caution/Monitor.
  
  opium tincture and amitriptyline both increase sedation. Use Caution/Monitor.

• orphenadrine

  Monitor Closely (3)amitriptyline and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  orphenadrine and perphenazine both increase sedation. Use Caution/Monitor.
  
  orphenadrine and amitriptyline both increase sedation. Use Caution/Monitor.

• osilodrostat

  Monitor Closely (1)osilodrostat and amitriptyline both increase QTc interval. Use Caution/Monitor.

• osimertinib

  Monitor Closely (2)osimertinib and perphenazine both increase QTc interval. Use Caution/Monitor. Conduct periodic monitoring with ECGs and electrolytes in patients taking drugs known to prolong the QTc interval.
  
  osimertinib and amitriptyline both increase QTc interval. Use Caution/Monitor. Conduct periodic monitoring with ECGs and electrolytes in patients taking drugs known to prolong the QTc interval.

• oxaliplatin

  Monitor Closely (2)oxaliplatin will increase the level or effect of amitriptyline by Other (see comment). Use Caution/Monitor. Monitor for ECG changes if therapy is initiated in patients with drugs known to prolong QT interval.
  
  oxaliplatin and perphenazine both increase QTc interval. Use Caution/Monitor.

• oxazepam

  Monitor Closely (2)oxazepam and perphenazine both increase sedation. Use Caution/Monitor.
  
  oxazepam and amitriptyline both increase sedation. Use Caution/Monitor.

• oxcarbazepine

  Minor (2)oxcarbazepine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.
  
  oxcarbazepine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• oxybutynin

  Monitor Closely (4)oxybutynin decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  oxybutynin decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  perphenazine increases effects of oxybutynin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  oxybutynin and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)oxybutynin increases toxicity of perphenazine by unspecified interaction mechanism. Minor/Significance Unknown.

• oxybutynin topical

  Monitor Closely (4)oxybutynin topical decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  perphenazine increases effects of oxybutynin topical by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  oxybutynin topical and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  oxybutynin topical decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.Minor (1)oxybutynin topical increases toxicity of perphenazine by unspecified interaction mechanism. Minor/Significance Unknown.

• oxybutynin transdermal

  Monitor Closely (4)oxybutynin transdermal decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  oxybutynin transdermal decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  perphenazine increases effects of oxybutynin transdermal by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  oxybutynin transdermal and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)oxybutynin transdermal increases toxicity of perphenazine by unspecified interaction mechanism. Minor/Significance Unknown.

• oxycodone

  Monitor Closely (3)oxycodone and perphenazine both increase sedation. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  oxycodone and amitriptyline both increase sedation. Use Caution/Monitor.Minor (1)perphenazine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

• oxymetazoline intranasal

  Monitor Closely (1)amitriptyline increases effects of oxymetazoline intranasal by pharmacodynamic synergism. Use Caution/Monitor. TCAs inhibit norepinephrine uptake in adrenergic neurons, thereby increasing synaptic norepinephrine levels. Coadministration with alpha1 agonists may cause increased adrenergic receptor stimulation. When oxymetazoline is combined with intranasal tetracaine for dental anesthesia, avoid or use alternant anesthetic in patients taking TCAs.

• oxymorphone

  Monitor Closely (3)oxymorphone and amitriptyline both increase sedation. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of oxymorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  oxymorphone and perphenazine both increase sedation. Use Caution/Monitor.

• ozanimod

  Monitor Closely (2)ozanimod and perphenazine both increase QTc interval. Modify Therapy/Monitor Closely. The potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties.
  
  ozanimod and amitriptyline both increase QTc interval. Modify Therapy/Monitor Closely. The potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties.Serious - Use Alternative (1)ozanimod increases toxicity of amitriptyline by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

• paliperidone

  Monitor Closely (5)amitriptyline and paliperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  paliperidone and perphenazine both increase sedation. Use Caution/Monitor.
  
  paliperidone and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  paliperidone and amitriptyline both increase sedation. Use Caution/Monitor.
  
  perphenazine and paliperidone both increase QTc interval. Modify Therapy/Monitor Closely.

• palonosetron

  Serious - Use Alternative (1)palonosetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• panax ginseng

  Minor (1)panax ginseng increases effects of amitriptyline by pharmacodynamic synergism. Minor/Significance Unknown.

• pancuronium

  Monitor Closely (4)pancuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine increases effects of pancuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  pancuronium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  pancuronium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• panobinostat

  Monitor Closely (1)panobinostat will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Panobinostat can increase the levels and effects of sensitive CYP2D6 substrates or those with a narrow therapeutic index CYP2D6.

• papaveretum

  Monitor Closely (2)papaveretum and perphenazine both increase sedation. Use Caution/Monitor.
  
  papaveretum and amitriptyline both increase sedation. Use Caution/Monitor.

• papaverine

  Monitor Closely (2)perphenazine and papaverine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and papaverine both increase sedation. Use Caution/Monitor.

• parecoxib

  Minor (2)parecoxib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  parecoxib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• paroxetine

  Monitor Closely (2)paroxetine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  amitriptyline and paroxetine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (4)paroxetine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
  
  perphenazine will increase the level or effect of paroxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
  
  perphenazine and paroxetine both increase QTc interval. Avoid or Use Alternate Drug.
  
  paroxetine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• pasireotide

  Monitor Closely (2)amitriptyline and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.
  
  perphenazine and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.

• pazopanib

  Monitor Closely (2)perphenazine and pazopanib both increase QTc interval. Use Caution/Monitor.
  
  amitriptyline and pazopanib both increase QTc interval. Use Caution/Monitor.

• peginterferon alfa 2b

  Monitor Closely (2)peginterferon alfa 2b, perphenazine. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.
  
  peginterferon alfa 2b, amitriptyline. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.

• pentamidine

  Contraindicated (2)perphenazine and pentamidine both increase QTc interval. Contraindicated.
  
  amitriptyline and pentamidine both increase QTc interval. Contraindicated.

• pentazocine

  Monitor Closely (3)amitriptyline and pentazocine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  pentazocine and perphenazine both increase sedation. Use Caution/Monitor.
  
  pentazocine and amitriptyline both increase sedation. Use Caution/Monitor.

• pentobarbital

  Monitor Closely (4)pentobarbital and perphenazine both increase sedation. Use Caution/Monitor.
  
  pentobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  pentobarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  pentobarbital and amitriptyline both increase sedation. Use Caution/Monitor.Minor (1)pentobarbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• perhexiline

  Minor (1)perphenazine will increase the level or effect of perhexiline by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• perindopril

  Minor (1)perphenazine increases effects of perindopril by unspecified interaction mechanism. Minor/Significance Unknown.

• perphenazine

  Monitor Closely (1)perphenazine and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)amitriptyline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amitriptyline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• phendimetrazine

  Monitor Closely (3)perphenazine, phendimetrazine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, phendimetrazine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• phenelzine

  Contraindicated (1)phenelzine and amitriptyline both increase serotonin levels. Contraindicated.Monitor Closely (1)phenelzine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• phenobarbital

  Monitor Closely (5)phenobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  phenobarbital and perphenazine both increase sedation. Use Caution/Monitor.
  
  phenobarbital and amitriptyline both increase sedation. Use Caution/Monitor.Minor (1)phenobarbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• phentermine

  Monitor Closely (3)perphenazine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine, phentermine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.Serious - Use Alternative (1)amitriptyline, phentermine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• phenylephrine

  Monitor Closely (3)perphenazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.Serious - Use Alternative (1)amitriptyline, phenylephrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• phenylephrine ophthalmic

  Monitor Closely (1)amitriptyline, phenylephrine ophthalmic. Other (see comment). Use Caution/Monitor. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• phenylephrine PO

  Monitor Closely (1)amitriptyline increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .Serious - Use Alternative (1)amitriptyline, phenylephrine PO. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• phenytoin

  Monitor Closely (2)phenytoin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor therapeutic efficacy of amitriptyline; an increased dose may be required. Serum phenytoin levels should be obtained when tricyclic antidepressant agents are added to therapy due to the potential for impaired phenytoin metabolism and decreased seizure threshold. Tricyclic antidepressants when given concomitantly with anticonvulsants can increase CNS depression.
  
  phenytoin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor therapeutic efficacy of amitriptyline; an increased dose may be required. Serum phenytoin levels should be obtained when tricyclic antidepressant agents are added to therapy due to the potential for impaired phenytoin metabolism and decreased seizure threshold. Tricyclic antidepressants when given concomitantly with anticonvulsants can increase CNS depression.

• pholcodine

  Monitor Closely (2)perphenazine and pholcodine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and pholcodine both increase sedation. Use Caution/Monitor.

• physostigmine

  Monitor Closely (1)physostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• pilocarpine

  Monitor Closely (1)pilocarpine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• pimozide

  Contraindicated (2)perphenazine and pimozide both increase QTc interval. Contraindicated.
  
  amitriptyline and pimozide both increase QTc interval. Contraindicated.Monitor Closely (3)perphenazine and pimozide both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  pimozide and amitriptyline both increase sedation. Use Caution/Monitor.
  
  perphenazine and pimozide both increase sedation. Use Caution/Monitor.

• pioglitazone

  Minor (1)amitriptyline increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• pirbuterol

  Monitor Closely (2)amitriptyline increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, pirbuterol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• pitolisant

  Serious - Use Alternative (1)amitriptyline decreases effects of pitolisant by Other (see comment). Avoid or Use Alternate Drug. Comment: Pitolisant increases histamine levels in the brain; therefore, H1 receptor antagonists that cross the blood-brain barrier may reduce the efficacy of pitolisant.

• pleurisy root

  Minor (1)pleurisy root decreases effects of amitriptyline by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.

• ponatinib

  Monitor Closely (1)ponatinib increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• porfimer

  Monitor Closely (1)perphenazine, porfimer. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced photosensitivity.

• posaconazole

  Monitor Closely (2)perphenazine and posaconazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  amitriptyline and posaconazole both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)posaconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pralidoxime

  Monitor Closely (4)perphenazine increases effects of pralidoxime by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  pralidoxime decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  pralidoxime decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  pralidoxime and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• pramipexole

  Serious - Use Alternative (1)perphenazine decreases effects of pramipexole by pharmacodynamic antagonism. Contraindicated.

• prednisone

  Minor (1)prednisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pregabalin

  Monitor Closely (1)pregabalin, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• primaquine

  Monitor Closely (1)primaquine and perphenazine both increase QTc interval. Use Caution/Monitor.

• primidone

  Monitor Closely (4)primidone will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  primidone and perphenazine both increase sedation. Use Caution/Monitor.
  
  primidone and amitriptyline both increase sedation. Use Caution/Monitor.
  
  primidone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.Minor (1)primidone, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• procainamide

  Contraindicated (2)amitriptyline and procainamide both increase QTc interval. Contraindicated.
  
  perphenazine and procainamide both increase QTc interval. Contraindicated.

• procarbazine

  Contraindicated (1)procarbazine and amitriptyline both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI use.Monitor Closely (2)procarbazine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  procarbazine, perphenazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Excessive sedation.

• prochlorperazine

  Monitor Closely (4)perphenazine and prochlorperazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  prochlorperazine and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  perphenazine and prochlorperazine both increase sedation. Use Caution/Monitor.
  
  prochlorperazine and amitriptyline both increase sedation. Use Caution/Monitor.Minor (3)amitriptyline, prochlorperazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amitriptyline, prochlorperazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  perphenazine will increase the level or effect of prochlorperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)perphenazine and prochlorperazine both increase QTc interval. Avoid or Use Alternate Drug.

• progesterone micronized

  Minor (1)progesterone micronized, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• promazine

  Serious - Use Alternative (2)promazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  perphenazine and promazine both increase QTc interval. Avoid or Use Alternate Drug.Minor (3)perphenazine will increase the level or effect of promazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  amitriptyline, promazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amitriptyline, promazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• promethazine

  Monitor Closely (5)promethazine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  promethazine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  perphenazine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  promethazine and perphenazine both increase sedation. Use Caution/Monitor.
  
  promethazine and amitriptyline both increase QTc interval. Use Caution/Monitor.Minor (3)perphenazine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  amitriptyline, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amitriptyline, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.Serious - Use Alternative (1)perphenazine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.

• propafenone

  Monitor Closely (2)perphenazine will increase the level or effect of propafenone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  propafenone will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• propantheline

  Monitor Closely (4)propantheline decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  perphenazine increases effects of propantheline by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  propantheline and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  propantheline decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

• propofol

  Monitor Closely (2)propofol and amitriptyline both increase sedation. Use Caution/Monitor.
  
  propofol and perphenazine both increase sedation. Use Caution/Monitor.Minor (1)propofol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• propranolol

  Monitor Closely (1)perphenazine will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• propylhexedrine

  Monitor Closely (3)amitriptyline increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine, propylhexedrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.Serious - Use Alternative (1)amitriptyline, propylhexedrine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• protriptyline

  Monitor Closely (3)amitriptyline and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine and protriptyline both increase sedation. Use Caution/Monitor.
  
  amitriptyline and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (3)perphenazine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.Minor (2)protriptyline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  protriptyline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• pseudoephedrine

  Monitor Closely (1)perphenazine, pseudoephedrine. Mechanism: unknown. Use Caution/Monitor. Consider avoiding use of pseudoephedrine in patients receiving phenothiazines (especially thioridazine) due to the potential risk of cardiac arrhythmia or sudden death. Monitor for evidence of ventricular arrhythmias during concomitant use.Serious - Use Alternative (1)amitriptyline increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• pyridostigmine

  Monitor Closely (1)pyridostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• pyrimethamine

  Minor (1)pyrimethamine increases levels of perphenazine by decreasing metabolism. Minor/Significance Unknown.

• quazepam

  Monitor Closely (2)quazepam and perphenazine both increase sedation. Use Caution/Monitor.
  
  quazepam and amitriptyline both increase sedation. Use Caution/Monitor.

• quercetin

  Monitor Closely (1)quercetin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• quetiapine

  Monitor Closely (4)quetiapine, amitriptyline. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Avoid use with drugs that prolong QT and in patients with risk factors for prolonged QT interval. Postmarketing cases show QT prolongation with overdose in patients with concomitant illness or with drugs known to cause electrolyte imbalance or prolong QT.
  
  quetiapine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  perphenazine and quetiapine both increase sedation. Use Caution/Monitor.
  
  perphenazine and quetiapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

• quinacrine

  Minor (1)quinacrine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• quinapril

  Minor (1)perphenazine increases effects of quinapril by unspecified interaction mechanism. Minor/Significance Unknown.

• quinidine

  Contraindicated (2)perphenazine and quinidine both increase QTc interval. Contraindicated.
  
  quinidine and amitriptyline both increase QTc interval. Contraindicated.Monitor Closely (1)quinidine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (2)quinidine, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Additive cardiac effects.
  
  quinidine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• quinine

  Monitor Closely (2)perphenazine and quinine both increase QTc interval. Use Caution/Monitor.
  
  amitriptyline and quinine both increase QTc interval. Use Caution/Monitor.

• quinupristin/dalfopristin

  Minor (1)quinupristin/dalfopristin will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• quizartinib

  Monitor Closely (2)quizartinib, amitriptyline. Either increases effects of the other by QTc interval. Modify Therapy/Monitor Closely. Monitor patients more frequently with ECG if coadministered with QT prolonging drugs.
  
  quizartinib, perphenazine. Either increases effects of the other by QTc interval. Modify Therapy/Monitor Closely. Monitor patients more frequently with ECG if coadministered with QT prolonging drugs.

• ramelteon

  Monitor Closely (2)perphenazine and ramelteon both increase sedation. Use Caution/Monitor.
  
  amitriptyline and ramelteon both increase sedation. Use Caution/Monitor.

• ramipril

  Minor (1)perphenazine increases effects of ramipril by unspecified interaction mechanism. Minor/Significance Unknown.

• ranolazine

  Monitor Closely (2)amitriptyline and ranolazine both increase QTc interval. Modify Therapy/Monitor Closely.
  
  perphenazine and ranolazine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)ranolazine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.Minor (1)ranolazine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• rapacuronium

  Monitor Closely (4)perphenazine increases effects of rapacuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  rapacuronium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  rapacuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  rapacuronium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

• rasagiline

  Serious - Use Alternative (1)rasagiline and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Severe CNS toxicity associated with hyperpyrexia has been reported with the combined treatment of an antidepressant and rasagiline. Avoid combination within 14 days of MAOI use.

• remifentanil

  Monitor Closely (1)amitriptyline, remifentanil. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. May also increase risk of serotonin syndrome.

• remimazolam

  Monitor Closely (2)remimazolam, amitriptyline. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.
  
  remimazolam, perphenazine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

• repaglinide

  Minor (1)amitriptyline increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• ribociclib

  Serious - Use Alternative (2)ribociclib increases toxicity of amitriptyline by QTc interval. Avoid or Use Alternate Drug.
  
  ribociclib increases toxicity of perphenazine by QTc interval. Avoid or Use Alternate Drug.

• rifabutin

  Monitor Closely (2)rifabutin decreases levels of amitriptyline by increasing metabolism. Use Caution/Monitor.
  
  rifabutin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rifampin

  Monitor Closely (3)rifampin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  rifampin will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  rifampin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rifapentine

  Monitor Closely (1)rifapentine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rilpivirine

  Monitor Closely (1)rilpivirine increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

• rimabotulinumtoxinB

  Monitor Closely (1)perphenazine, rimabotulinumtoxinB. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Anticholinergics may enhance botulinum toxin effects. Closely monitor for increased neuromuscular blockade.

• risperidone

  Monitor Closely (5)amitriptyline and risperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  risperidone and amitriptyline both increase sedation. Use Caution/Monitor.
  
  perphenazine and risperidone both increase sedation. Use Caution/Monitor.
  
  perphenazine and risperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  perphenazine and risperidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.Minor (1)perphenazine will increase the level or effect of risperidone by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• ritonavir

  Monitor Closely (2)ritonavir will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ritonavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)ritonavir will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• rivastigmine

  Monitor Closely (1)rivastigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• rizatriptan

  Monitor Closely (2)rizatriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  rizatriptan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• rocuronium

  Monitor Closely (4)rocuronium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  rocuronium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  rocuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine increases effects of rocuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• rolapitant

  Monitor Closely (2)rolapitant will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.
  
  rolapitant will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.

• romidepsin

  Monitor Closely (2)perphenazine and romidepsin both increase QTc interval. Modify Therapy/Monitor Closely.
  
  amitriptyline and romidepsin both increase QTc interval. Modify Therapy/Monitor Closely.

• ropinirole

  Serious - Use Alternative (1)perphenazine decreases effects of ropinirole by pharmacodynamic antagonism. Contraindicated.

• rosiglitazone

  Minor (1)amitriptyline increases effects of rosiglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• rufinamide

  Minor (1)rufinamide will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• safinamide

  Contraindicated (1)amitriptyline, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.Serious - Use Alternative (1)perphenazine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

• sage

  Minor (2)perphenazine and sage both increase sedation. Minor/Significance Unknown.
  
  amitriptyline and sage both increase sedation. Minor/Significance Unknown.

• salmeterol

  Monitor Closely (2)perphenazine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, salmeterol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• SAMe

  Monitor Closely (1)amitriptyline and SAMe both increase serotonin levels. Modify Therapy/Monitor Closely.

• saquinavir

  Serious - Use Alternative (1)saquinavir, perphenazine. Either increases toxicity of the other by QTc interval. Avoid or Use Alternate Drug. Increased risk of PR or QT prolongation and cardiac arrhythmias.

• sarecycline

  Monitor Closely (1)sarecycline will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

• saxagliptin

  Minor (1)amitriptyline increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

• scopolamine

  Monitor Closely (4)scopolamine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  scopolamine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  perphenazine increases effects of scopolamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  scopolamine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• scullcap

  Monitor Closely (2)perphenazine and scullcap both increase sedation. Use Caution/Monitor.
  
  amitriptyline and scullcap both increase sedation. Use Caution/Monitor.

• secobarbital

  Monitor Closely (3)secobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  secobarbital and amitriptyline both increase sedation. Use Caution/Monitor.
  
  secobarbital and perphenazine both increase sedation. Use Caution/Monitor.Minor (1)secobarbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• selegiline

  Contraindicated (1)selegiline and amitriptyline both increase serotonin levels. Contraindicated. Concurrent use or use within 14 days of selegiline treatment is contraindicatedMonitor Closely (1)selegiline, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• selegiline transdermal

  Serious - Use Alternative (1)selegiline transdermal and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• selinexor

  Serious - Use Alternative (2)selinexor, amitriptyline. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.
  
  selinexor, perphenazine. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

• selpercatinib

  Monitor Closely (2)selpercatinib increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor.
  
  selpercatinib increases toxicity of perphenazine by QTc interval. Use Caution/Monitor.

• serdexmethylphenidate/dexmethylphenidate

  Monitor Closely (1)perphenazine, serdexmethylphenidate/dexmethylphenidate. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.Serious - Use Alternative (1)amitriptyline, serdexmethylphenidate/dexmethylphenidate. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.Minor (1)serdexmethylphenidate/dexmethylphenidate increases effects of amitriptyline by decreasing metabolism. Minor/Significance Unknown.

• sertraline

  Monitor Closely (2)sertraline and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  sertraline and amitriptyline both increase QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)sertraline and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.Minor (1)sertraline will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• sevoflurane

  Monitor Closely (4)sevoflurane and amitriptyline both increase sedation. Use Caution/Monitor.
  
  sevoflurane and perphenazine both increase sedation. Use Caution/Monitor.
  
  sevoflurane and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  sevoflurane and perphenazine both increase QTc interval. Use Caution/Monitor.Minor (1)sevoflurane, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• shepherd's purse

  Monitor Closely (2)perphenazine and shepherd's purse both increase sedation. Use Caution/Monitor.
  
  amitriptyline and shepherd's purse both increase sedation. Use Caution/Monitor.

• simvastatin

  Monitor Closely (1)simvastatin will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• siponimod

  Monitor Closely (1)siponimod and perphenazine both increase QTc interval. Use Caution/Monitor.

• sirolimus

  Monitor Closely (1)sirolimus will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• sitagliptin

  Minor (1)amitriptyline increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

• smoking

  Monitor Closely (1)smoking decreases levels of perphenazine by increasing metabolism. Use Caution/Monitor. Interaction mainly seen w/chlorpromazine & thioridazine, but may occur w/other phenothiazines.

• sodium oxybate

  Serious - Use Alternative (2)amitriptyline, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.
  
  perphenazine, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• sodium sulfate/?magnesium sulfate/potassium chloride

  Monitor Closely (2)sodium sulfate/?magnesium sulfate/potassium chloride increases effects of amitriptyline by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of seizures when using higher dose of magnesium sulfate together with drugs that lower the seizure threshold.
  
  sodium sulfate/?magnesium sulfate/potassium chloride increases effects of perphenazine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.

• sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol

  Monitor Closely (1)amitriptyline, sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol. Other (see comment). Use Caution/Monitor. Comment: Caution when bowel preps are used with drugs that cause SIADH or NSAIDs; increased risk for water retention or electrolyte imbalance.

• sodium sulfate/potassium sulfate/magnesium sulfate

  Monitor Closely (2)sodium sulfate/potassium sulfate/magnesium sulfate increases effects of amitriptyline by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of seizures when using higher dose of magnesium sulfate together with drugs that lower the seizure threshold.
  
  sodium sulfate/potassium sulfate/magnesium sulfate increases effects of perphenazine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.

• solifenacin

  Monitor Closely (6)solifenacin and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  solifenacin and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  solifenacin decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  solifenacin and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  solifenacin decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of solifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• sorafenib

  Monitor Closely (2)sorafenib and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  sorafenib and perphenazine both increase QTc interval. Use Caution/Monitor.

• sotalol

  Contraindicated (2)perphenazine and sotalol both increase QTc interval. Contraindicated.
  
  amitriptyline and sotalol both increase QTc interval. Contraindicated.

• St John's Wort

  Monitor Closely (2)St John's Wort will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  St John's Wort will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)amitriptyline and St John's Wort both increase serotonin levels. Avoid or Use Alternate Drug.

• stiripentol

  Monitor Closely (2)stiripentol, perphenazine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.
  
  stiripentol, amitriptyline. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

• succinylcholine

  Monitor Closely (1)succinylcholine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• sufentanil

  Monitor Closely (2)sufentanil and amitriptyline both increase sedation. Use Caution/Monitor.
  
  sufentanil and perphenazine both increase sedation. Use Caution/Monitor.

• sufentanil SL

  Monitor Closely (1)sufentanil SL, amitriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.Serious - Use Alternative (1)sufentanil SL, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• sulfamethoxazole

  Monitor Closely (2)amitriptyline and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  perphenazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)sulfamethoxazole decreases levels of amitriptyline by unspecified interaction mechanism. Minor/Significance Unknown.

• sumatriptan

  Monitor Closely (2)sumatriptan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  sumatriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• sumatriptan intranasal

  Monitor Closely (2)sumatriptan intranasal, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  sumatriptan intranasal and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• sunitinib

  Monitor Closely (1)sunitinib and perphenazine both increase QTc interval. Use Caution/Monitor.

• suvorexant

  Monitor Closely (1)suvorexant and amitriptyline both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary

• tacrolimus

  Monitor Closely (2)tacrolimus and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  tacrolimus will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• tamoxifen

  Monitor Closely (1)perphenazine decreases effects of tamoxifen by decreasing metabolism. Use Caution/Monitor. Inhibition of CYP2D6 metabolism to tamoxifen's active metabolite, endoxifen.

• tapentadol

  Monitor Closely (3)tapentadol and perphenazine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  tapentadol and amitriptyline both increase sedation. Use Caution/Monitor.

• tedizolid

  Serious - Use Alternative (1)tedizolid, amitriptyline. Either increases effects of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. both increase serotonin levels; increased risk of serotonin syndrome.

• telavancin

  Monitor Closely (2)perphenazine and telavancin both increase QTc interval. Modify Therapy/Monitor Closely.
  
  amitriptyline and telavancin both increase QTc interval. Modify Therapy/Monitor Closely.

• temazepam

  Monitor Closely (2)temazepam and amitriptyline both increase sedation. Use Caution/Monitor.
  
  temazepam and perphenazine both increase sedation. Use Caution/Monitor.

• terbinafine

  Monitor Closely (2)terbinafine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.
  
  terbinafine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.

• terbutaline

  Monitor Closely (2)perphenazine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, terbutaline. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• teriflunomide

  Monitor Closely (1)teriflunomide decreases levels of amitriptyline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• tetrabenazine

  Monitor Closely (2)perphenazine and tetrabenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely.
  
  tetrabenazine and amitriptyline both increase QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)tetrabenazine and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.

• thioridazine

  Monitor Closely (3)perphenazine and thioridazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  thioridazine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  perphenazine and thioridazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (3)perphenazine and thioridazine both increase QTc interval. Avoid or Use Alternate Drug.
  
  thioridazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  perphenazine will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.Minor (3)amitriptyline, thioridazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amitriptyline, thioridazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  thioridazine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• thiothixene

  Monitor Closely (3)perphenazine and thiothixene both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  perphenazine and thiothixene both increase sedation. Use Caution/Monitor.
  
  thiothixene and amitriptyline both increase sedation. Use Caution/Monitor.

• thyroid desiccated

  Monitor Closely (1)thyroid desiccated increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• timolol

  Monitor Closely (1)perphenazine will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• tiotropium

  Monitor Closely (4)tiotropium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  tiotropium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  tiotropium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  perphenazine increases effects of tiotropium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• tipranavir

  Minor (1)tipranavir will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• tobacco use

  Monitor Closely (1)tobacco use decreases levels of perphenazine by increasing metabolism. Use Caution/Monitor. Interaction mainly seen w/chlorpromazine & thioridazine, but may occur w/other phenothiazines.

• tolazamide

  Minor (1)amitriptyline increases effects of tolazamide by pharmacodynamic synergism. Minor/Significance Unknown.

• tolbutamide

  Minor (1)amitriptyline increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

• tolterodine

  Monitor Closely (4)tolterodine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of tolterodine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  tolterodine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  tolterodine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)perphenazine will increase the level or effect of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• tolvaptan

  Monitor Closely (1)tolvaptan will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• topiramate

  Monitor Closely (3)amitriptyline and topiramate both increase sedation. Modify Therapy/Monitor Closely.
  
  perphenazine and topiramate both increase sedation. Modify Therapy/Monitor Closely.
  
  topiramate increases toxicity of amitriptyline by unspecified interaction mechanism. Use Caution/Monitor. Amitriptyline levels may increase; adjust dose based on clinical response and not on basis of plasma levels.

• toremifene

  Serious - Use Alternative (1)amitriptyline and toremifene both increase QTc interval. Avoid or Use Alternate Drug. Concurrent use of toremifene with agents causing QT prolongation should be avoided. If concomitant use is required it's recommended that toremifene be interrupted. If interruption not possible, patients requiring therapy with a drug that prolongs QT should be closely monitored. ECGs should be obtained for high risk patients.

• tramadol

  Monitor Closely (3)tramadol and perphenazine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  tramadol and amitriptyline both increase sedation. Use Caution/Monitor.

• trandolapril

  Minor (1)perphenazine increases effects of trandolapril by unspecified interaction mechanism. Minor/Significance Unknown.

• tranylcypromine

  Contraindicated (1)tranylcypromine and amitriptyline both increase serotonin levels. Contraindicated.Monitor Closely (1)tranylcypromine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• trazodone

  Monitor Closely (4)amitriptyline and trazodone both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  trazodone will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  perphenazine and trazodone both increase sedation. Use Caution/Monitor.
  
  amitriptyline and trazodone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (3)perphenazine and trazodone both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and trazodone both increase QTc interval. Avoid or Use Alternate Drug.
  
  trazodone and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.Minor (2)trazodone, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  trazodone, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.

• tretinoin

  Serious - Use Alternative (1)perphenazine, tretinoin. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

• tretinoin topical

  Serious - Use Alternative (1)perphenazine, tretinoin topical. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

• triazolam

  Monitor Closely (2)triazolam and perphenazine both increase sedation. Use Caution/Monitor.
  
  triazolam and amitriptyline both increase sedation. Use Caution/Monitor.

• triclofos

  Monitor Closely (2)triclofos and perphenazine both increase sedation. Use Caution/Monitor.
  
  triclofos and amitriptyline both increase sedation. Use Caution/Monitor.

• trifluoperazine

  Monitor Closely (3)perphenazine and trifluoperazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  perphenazine and trifluoperazine both increase sedation. Use Caution/Monitor.
  
  trifluoperazine and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)perphenazine and trifluoperazine both increase QTc interval. Avoid or Use Alternate Drug.
  
  trifluoperazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (3)perphenazine will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  amitriptyline, trifluoperazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amitriptyline, trifluoperazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• trihexyphenidyl

  Monitor Closely (3)trihexyphenidyl decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  trihexyphenidyl and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. Potential for additive anticholinergic effects.
  
  perphenazine increases effects of trihexyphenidyl by pharmacodynamic synergism. Use Caution/Monitor. Potential for additive anticholinergic effects.

• trimethoprim

  Monitor Closely (2)perphenazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.
  
  amitriptyline and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• trimipramine

  Monitor Closely (3)perphenazine and trimipramine both increase sedation. Use Caution/Monitor.
  
  amitriptyline and trimipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  amitriptyline and trimipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (3)perphenazine and trimipramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and trimipramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and trimipramine both increase serotonin levels. Avoid or Use Alternate Drug.Minor (2)trimipramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  trimipramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• triprolidine

  Monitor Closely (2)triprolidine and perphenazine both increase sedation. Use Caution/Monitor.
  
  triprolidine and amitriptyline both increase sedation. Use Caution/Monitor.

• tropisetron

  Monitor Closely (2)perphenazine and tropisetron both increase QTc interval. Modify Therapy/Monitor Closely.
  
  amitriptyline and tropisetron both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)perphenazine will increase the level or effect of tropisetron by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• trospium chloride

  Monitor Closely (4)trospium chloride decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  trospium chloride and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  perphenazine increases effects of trospium chloride by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  trospium chloride decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

• tucatinib

  Monitor Closely (1)tucatinib will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

• umeclidinium bromide/vilanterol inhaled

  Serious - Use Alternative (3)amitriptyline and umeclidinium bromide/vilanterol inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Exercise extreme caution if vilanterol coadministered with MAOIs or TCAs, or within 2 weeks of discontinuation of these drugs; adrenergic agonist effects on the cardiovascular system may be potentiated
  
  amitriptyline increases toxicity of umeclidinium bromide/vilanterol inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.
  
  perphenazine increases toxicity of umeclidinium bromide/vilanterol inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.

• valbenazine

  Monitor Closely (2)valbenazine and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  valbenazine and perphenazine both increase QTc interval. Use Caution/Monitor.

• valerian

  Monitor Closely (1)valerian and amitriptyline both increase sedation. Use Caution/Monitor.

• vandetanib

  Serious - Use Alternative (1)amitriptyline, vandetanib. Either increases toxicity of the other by QTc interval. Avoid or Use Alternate Drug. Avoid coadministration with drugs known to prolong QT interval; if a drug known to prolong QT interval must be used, more frequent ECG monitoring is recommended.

• vasopressin

  Minor (1)amitriptyline increases effects of vasopressin by pharmacodynamic synergism. Minor/Significance Unknown.

• vecuronium

  Monitor Closely (4)vecuronium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of vecuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  vecuronium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  vecuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• vemurafenib

  Serious - Use Alternative (1)vemurafenib and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.

• venlafaxine

  Monitor Closely (3)venlafaxine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  amitriptyline and venlafaxine both increase QTc interval. Modify Therapy/Monitor Closely.
  
  venlafaxine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (2)venlafaxine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.
  
  perphenazine and venlafaxine both increase QTc interval. Avoid or Use Alternate Drug.

• verapamil

  Monitor Closely (1)verapamil will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. The frequency and severity of amitriptyline adverse effects (sedation, anticholinergic effects and orthostatic hypotension) may be increased. Cardiac dysrhythmic effects may be additive. Minor (2)verapamil will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  verapamil increases levels of amitriptyline by decreasing metabolism. Minor/Significance Unknown.

• vilanterol/fluticasone furoate inhaled

  Serious - Use Alternative (3)amitriptyline and vilanterol/fluticasone furoate inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Exercise extreme caution if vilanterol coadministered with MAOIs or TCAs, or within 2 weeks of discontinuation of these drugs; adrenergic agonist effects on the cardiovascular system may be potentiated
  
  amitriptyline increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.
  
  perphenazine increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.

• vilazodone

  Monitor Closely (1)vilazodone, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).Serious - Use Alternative (1)amitriptyline, vilazodone. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Concomitant therapy should be discontinued immediately if signs or symptoms of serotonin syndrome emerge and supportive symptomatic treatment should be initiated. .

• vildagliptin

  Minor (1)amitriptyline increases effects of vildagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

• voclosporin

  Monitor Closely (1)voclosporin, amitriptyline. Either increases effects of the other by QTc interval. Use Caution/Monitor.

• voriconazole

  Monitor Closely (3)perphenazine and voriconazole both increase QTc interval. Modify Therapy/Monitor Closely.
  
  voriconazole will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  amitriptyline and voriconazole both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)voriconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vorinostat

  Monitor Closely (1)vorinostat and perphenazine both increase QTc interval. Use Caution/Monitor.

• vortioxetine

  Serious - Use Alternative (1)amitriptyline, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.

• warfarin

  Monitor Closely (1)amitriptyline increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.

• xylometazoline

  Monitor Closely (3)perphenazine, xylometazoline. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  amitriptyline increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, xylometazoline. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• yohimbe

  Serious - Use Alternative (2)yohimbe, amitriptyline. Mechanism: unspecified interaction mechanism. Contraindicated. May cause increase or decrease in blood pressure.
  
  yohimbe decreases effects of perphenazine by pharmacodynamic antagonism. Contraindicated.

• yohimbine

  Monitor Closely (3)amitriptyline increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  perphenazine, yohimbine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, yohimbine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• zafirlukast

  Minor (1)zafirlukast will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ziconotide

  Monitor Closely (2)amitriptyline and ziconotide both increase sedation. Use Caution/Monitor.
  
  perphenazine and ziconotide both increase sedation. Use Caution/Monitor.

• ziprasidone

  Monitor Closely (3)ziprasidone and amitriptyline both increase sedation. Use Caution/Monitor.
  
  perphenazine and ziprasidone both increase sedation. Use Caution/Monitor.
  
  perphenazine and ziprasidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.Serious - Use Alternative (2)perphenazine and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.

• zolmitriptan

  Monitor Closely (2)zolmitriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  zolmitriptan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• zolpidem

  Monitor Closely (1)perphenazine will increase the level or effect of zolpidem by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Additive effect of decreased alertness and psychomotor performanceMinor (1)zolpidem, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.

• zotepine

  Monitor Closely (2)perphenazine and zotepine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  perphenazine and zotepine both increase sedation. Use Caution/Monitor.