Dosing & Uses
Dosage Forms & Strengths
amitriptyline/perphenazine
tablet
- 10mg/2mg
- 25mg/2mg
- 10mg/4mg
- 25mg/4mg
- 50mg/4mg
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
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

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.
Frequency Not Defined
Sedation
Fatigue
Constipation
Dry mouth
Lethargy
Weakness
Anticholinergic effects
Blurred vision
Lens opacities
Orthostatic hypotension
Agitation
Anxiety
Headache
Insomnia
Nausea/vomiting
Sweating
Orthostatic hypotension
ECG changes
Tachycardia
Confusion
EPS
Dizziness
Paresthesia
Rash
Increased LFTs
Sexual dysfunction
Tinnitus
Seizure
Agranulocytosis
Thrombocytopenia
Eosinophilia
Leukopenia
SIADH
Antipsychotic side effects
Poikilothermia
Decreased gag reflex
Weight gain
Amenorrhea
Post Marketing Reports
Neuroleptic malignant syndrome
Serotonin syndrome
Warnings
Black Box Warnings
Children & Antidepressants
- In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (< 24 years of age) taking antidepressants for major depressive disorders and other psychiatric illnesses. This increase was not seen in patients >24 years of age. A slight decrease in suicidal thinking was seen in adults >65 years. Risks must be weighed in children and young adults against the benefits of taking antidepressants. Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies. This should be done during the initial 1-2 months of therapy and dosage adjustments. The patient’s family should communicate to the healthcare provider any abrupt changes in behavior. Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy. This drug is not approved for use in pediatric patients.
Antipsychotics & Dementia
- Patients with dementia-related psychosis that are treated with antipsychotic drugs are at an increased risk of death as shown in short-term controlled trials. The deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. This drug is not approved for the treatment of patients with dementia-related psychosis (See WARNINGS in package insert).
Contraindications
Tricyclic Antidepressant (amitriptyline): hypersensitivity, severe cardiovascular disorder, narrow angle glaucoma, within 14 days of MAOIs (risk of serotonin syndrome), any drugs or conditions that prolong QT interval, acute recovery post-MI
Antipsychotic (perphenazine): hypersensitivity, CNS depression, neuroleptic malignant syndrome, poorly controlled seizure disorder, subcortical braine damage, coma, severe obtundation, high dose CNS depressants, blood dyscrasia, myelosuppression, liver damage
Pregnancy & Lactation
Pregnancy Category: D
Lactation: excreted in breast milk; not recommended
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Amitriptyline: Antidepressant; neurotransmitter (especially norepinephrine and serotonin) reuptake inhibitor; elicits anticholinergic effects
Perphenazine: Antipsychotic agent; elicits moderate anticholinergic effects, weak to moderate sedative effects, strong extrapyramidal effects, and strong antiemetic activity
Pharmacokinetics
Amitriptyline
- Onset of action: 6 weeks
- Half-life: 9-27 hr
- Peak serum time: 4 hr
- Metabolism: Hepatic (CYP2C19, CYP3A4)
- Excretion: Urine (25-50%); bile (small amounts)
Perphenazine
- Half-life: 9-12 hr
- Peak plasma time: 1-3 hr; 2-4 hr (metabolite)
- Metabolism: Hepatic P450 enzyme (CYP2D6)
- Excretion: Urine; feces
Images
Formulary
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