perphenazine (Rx)

Intractable Hiccoughs (Off-label)

8-16 mg PO qDay divided q8-12hr

Maximum: 24 mg

Treatment of Nausea/Vomiting

8-16 mg PO qDay divided q6-12hr

Maximum: 24 mg

Schizophrenia

Hospitalized patients: 8-16mg PO q6-12hr

Hospitalized patients: Not to exceed 64 mg/day divided q6-12hr

Outpatients: 4-8mg PO q8hr; reduce as soon as possible to minimum effective dose

Hepatic Impairment

Dose adjustment not described in manufacturer's labeling

Renal Impairment

Dose adjustment not described in manufacturer's labeling

Intractable Hiccoughs (Off-label)

<12 years

• Not recommended by manufacturer

>12 years

• 8-16 mg PO qDay divided q8-12hr Maximum: 24 mg

Schizophrenia

<12 years

• Not recommended by manufacturer

>12 years

• Hospitalized patients: 8-16mg PO q6-12hr
• Hospitalized patients: Not to exceed 64 mg/day divided q6-12hr
• Outpatients: 4-8mg PO q8hr; reduce as soon as possible to minimum effective dose

Initiate dosing at lower end of the range

Intractable Hiccoughs

8-16 mg PO qDay divided q8-12hr

Maximum: 24 mg

Treatment of Nausea/Vomiting

8-16 mg PO qDay divided q6-12hr

Maximum: 24 mg

Schizophrenia

Hospitalized patients: 8-16mg PO q6-12hr

Hospitalized patients: Not to exceed 64 mg/day divided q6-12hr

Outpatients: 4-8mg PO q8hr; reduce as soon as possible to minimum effective dose

Contraindicated (11)

• amisulpride

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

• disopyramide

  perphenazine and disopyramide both increase QTc interval. 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

• ibutilide

  perphenazine and ibutilide both increase QTc interval. Contraindicated.

• indapamide

  perphenazine and indapamide both increase QTc interval. Contraindicated.

• metrizamide

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

• pentamidine

  perphenazine and pentamidine both increase QTc interval. Contraindicated.

• pimozide

  perphenazine and pimozide both increase QTc interval. Contraindicated.

• procainamide

  perphenazine and procainamide both increase QTc interval. Contraindicated.

• quinidine

  perphenazine and quinidine both increase QTc interval. Contraindicated.

• sotalol

  perphenazine and sotalol both increase QTc interval. Contraindicated.

Serious - Use Alternative (96)

• adagrasib

  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.

• 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

  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.

• 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.

• aripiprazole

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

• arsenic trioxide

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

• artemether/lumefantrine

  perphenazine 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).

• bromocriptine

  perphenazine decreases effects of bromocriptine by pharmacodynamic antagonism. 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.

• chlorpromazine

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

• clarithromycin

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

• clomipramine

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

• 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.

• 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.

• dofetilide

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

• dopamine

  perphenazine decreases effects of dopamine by pharmacodynamic antagonism. Contraindicated.

• dosulepin

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

• doxepin

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

• dronedarone

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

• droperidol

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

• epinephrine

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

• epinephrine racemic

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

• erythromycin base

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

• erythromycin ethylsuccinate

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

• erythromycin lactobionate

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

• erythromycin stearate

  perphenazine and erythromycin stearate both increase 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.

• 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.

• fluconazole

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

• fluoxetine

  fluoxetine 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 fluoxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
  
  perphenazine and fluoxetine both increase QTc interval. Avoid or Use Alternate Drug.

• fluphenazine

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

• formoterol

  perphenazine and formoterol both increase QTc interval. 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.

• haloperidol

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

• imipramine

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

• isocarboxazid

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

• 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.

• ketoconazole

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

• levodopa

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

• 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.

• lisuride

  perphenazine decreases effects of lisuride by pharmacodynamic antagonism. Contraindicated.

• lofepramine

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

• lorcaserin

  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.

• 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

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

• 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.

• methyldopa

  perphenazine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

• 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.

• 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.

• moxifloxacin

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

• nilotinib

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

• nortriptyline

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

• octreotide

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

• octreotide (Antidote)

  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.

• 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.

• 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.

• pramipexole

  perphenazine decreases effects of pramipexole by pharmacodynamic antagonism. Contraindicated.

• prochlorperazine

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

• promazine

  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.

• protriptyline

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

• quinidine

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

• ribociclib

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

• ropinirole

  perphenazine decreases effects of ropinirole by pharmacodynamic antagonism. Contraindicated.

• 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.

• selinexor

  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.

• 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.

• 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.

• tetrabenazine

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

• thioridazine

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

• trazodone

  perphenazine and trazodone both increase QTc interval. 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.

• trimipramine

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

• umeclidinium bromide/vilanterol inhaled

  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.

• venlafaxine

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

• vilanterol/fluticasone furoate inhaled

  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.

• yohimbe

  yohimbe decreases effects of perphenazine by pharmacodynamic antagonism. Contraindicated.

• ziprasidone

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

Monitor Closely (363)

• 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.

• abobotulinumtoxinA

  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.
  
  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.

• 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

  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.

• alfuzosin

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

• alprazolam

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

• amifampridine

  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.

• amitriptyline

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

• amobarbital

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

• amoxapine

  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.

• anagrelide

  anagrelide and perphenazine both increase QTc interval. 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

  perphenazine and apomorphine both increase sedation. 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.

• aripiprazole

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

• armodafinil

  perphenazine 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.

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

• atracurium

  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.
  
  perphenazine increases effects of atracurium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• atropine

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

• atropine IV/IM

  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 inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  atropine IV/IM decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

• avapritinib

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

• azelastine

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

• azithromycin

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

• baclofen

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

• bedaquiline

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

• belladonna alkaloids

  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.
  
  perphenazine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• 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.
  
  belladonna and opium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of belladonna and opium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• benperidol

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

• benzhydrocodone/acetaminophen

  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.
  
  benzhydrocodone/acetaminophen and perphenazine both increase sedation. Use Caution/Monitor.

• benzphetamine

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

• benztropine

  perphenazine increases effects of benztropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic adverse effects may be seen with concurrent use. .

• brexanolone

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

• brexpiprazole

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

• brimonidine

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

• brivaracetam

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

• brompheniramine

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

• buprenorphine

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

• buprenorphine buccal

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

• buprenorphine subdermal implant

  buprenorphine subdermal implant and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  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

  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.

• bupropion

  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.

• butabarbital

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

• butalbital

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

• butorphanol

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

• caffeine

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

• carbinoxamine

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

• carisoprodol

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

• ceritinib

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

• chloral hydrate

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

• chlordiazepoxide

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

• chlorpheniramine

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

• chlorpromazine

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

• chlorzoxazone

  chlorzoxazone and perphenazine 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.

• cinnarizine

  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.

• citalopram

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

• clemastine

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

• clobazam

  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

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

• clonazepam

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

• clonidine

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

• clorazepate

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

• clozapine

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

• codeine

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

• crizotinib

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

• cyclizine

  cyclizine and perphenazine both increase sedation. Use Caution/Monitor.
  
  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.
  
  perphenazine increases effects of cyclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• cyclobenzaprine

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

• cyproheptadine

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

• dantrolene

  dantrolene and perphenazine 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.

• darifenacin

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

• dasatinib

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

• desflurane

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

• desipramine

  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.

• 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

  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 perphenazine both increase sedation. Use Caution/Monitor.

• dexfenfluramine

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

• dexmedetomidine

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

• dexmethylphenidate

  perphenazine 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

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

• dextroamphetamine transdermal

  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 perphenazine both increase sedation. Use Caution/Monitor.

• diamorphine

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

• diazepam

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

• 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.

• diethylpropion

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

• difelikefalin

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

• difenoxin hcl

  difenoxin hcl and perphenazine 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).

• dimenhydrinate

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

• diphenhydramine

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

• diphenoxylate hcl

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

• dipipanone

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

• dobutamine

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

• dofetilide

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

• dolasetron

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

• donepezil

  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

  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.

• dosulepin

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

• doxepin

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

• doxylamine

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

• droperidol

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

• efavirenz

  efavirenz and perphenazine both increase QTc interval. 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).

• eliglustat

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

• 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.

• encorafenib

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

• entrectinib

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

• ephedrine

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

• epinephrine

  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.
  
  perphenazine decreases effects of epinephrine by pharmacodynamic antagonism. Use Caution/Monitor. Block pressor response to epinephrine, which may result in severe hypotension and tachycardia.

• 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.

• 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).

• eribulin

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

• escitalopram

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

• estazolam

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

• ethanol

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

• etomidate

  etomidate and perphenazine both increase sedation. 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.

• fenfluramine

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

• 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 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.

• flavoxate

  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.
  
  perphenazine increases effects of flavoxate by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• flecainide

  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).

• fluphenazine

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

• flurazepam

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

• fluvoxamine

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

• formoterol

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

• foscarnet

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

• 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).

• ganaxolone

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

• gemifloxacin

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

• gilteritinib

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

• 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 inhaled

  glycopyrrolate inhaled decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. 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.
  
  perphenazine increases toxicity of glycopyrrolate inhaled by unknown mechanism. Use Caution/Monitor.

• glycopyrronium tosylate topical

  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.

• guanfacine

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

• haloperidol

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

• 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.

• 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.

• hydroxyzine

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

• hyoscyamine

  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 decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  hyoscyamine spray decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

• iloperidone

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

• imipramine

  perphenazine will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  perphenazine and imipramine both increase sedation. 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, perphenazine. QTc interval. Use Caution/Monitor. Drugs that are known to prolong the QTc interval may have an increased the risk of ventricular arrhythmias.

• 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 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 perphenazine both increase QTc interval. Use Caution/Monitor.

• 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.

• ketamine

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

• ketotifen, ophthalmic

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

• lapatinib

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

• lasmiditan

  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.

• 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.

• levalbuterol

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

• levofloxacin

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

• 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 perphenazine both increase sedation. Use Caution/Monitor.

• 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).

• 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

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

• lithium

  lithium, perphenazine. Other (see comment). Use Caution/Monitor. Comment: Risk of neurotoxicity. Multiple mechanisms involved.
  
  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).
  
  lithium and perphenazine both increase QTc interval. Use Caution/Monitor.

• lofepramine

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

• lofexidine

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

• loprazolam

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

• lorazepam

  lorazepam and perphenazine 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, 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.

• loxapine

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

• loxapine inhaled

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

• lumefantrine

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

• lurasidone

  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.

• maprotiline

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

• marijuana

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

• 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.

• melatonin

  perphenazine 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).

• meprobamate

  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.

• metaxalone

  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

  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 will increase the level or effect of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  perphenazine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  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.

• methocarbamol

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

• 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

  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.

• 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 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.

• midodrine

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

• mifepristone

  mifepristone, perphenazine. 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).

• mirabegron

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

• mirtazapine

  perphenazine 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.

• morphine

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

• motherwort

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

• moxonidine

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

• nabilone

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

• nalbuphine

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

• naratriptan

  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.

• norepinephrine

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

• nortriptyline

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

• ofloxacin

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

• olanzapine

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

• oliceridine

  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).

• olodaterol inhaled

  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 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.

• orphenadrine

  orphenadrine and perphenazine both increase sedation. 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.

• oxaliplatin

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

• oxazepam

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

• oxybutynin

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

• oxybutynin topical

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

• oxybutynin transdermal

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

• oxycodone

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

• 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.

• 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.

• paliperidone

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

• pancuronium

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

• 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 perphenazine both increase sedation. Use Caution/Monitor.

• papaverine

  perphenazine 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).

• pasireotide

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

• pazopanib

  perphenazine 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.

• pentazocine

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

• pentobarbital

  pentobarbital and perphenazine 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.

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

• phentermine

  perphenazine 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.
  
  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.

• pholcodine

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

• 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.

• pirbuterol

  perphenazine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. 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.

• pralidoxime

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

• primaquine

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

• primidone

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

• 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

  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

  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, 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).

• 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 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 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

  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

  perphenazine 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.

• quazepam

  quazepam and perphenazine both increase sedation. 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.

• 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.

• ramelteon

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

• ranolazine

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

• rapacuronium

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

• 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.

• 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

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

• rocuronium

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

• 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.

• romidepsin

  perphenazine 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.

• 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.

• scullcap

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

• secobarbital

  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 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.

• sevoflurane

  sevoflurane and perphenazine both increase sedation. 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.

• siponimod

  siponimod and perphenazine both increase QTc interval. 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 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 perphenazine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.

• solifenacin

  solifenacin decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. 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.
  
  solifenacin and perphenazine both increase QTc interval. Use Caution/Monitor.

• sorafenib

  sorafenib and perphenazine both increase QTc interval. 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.

• sufentanil

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

• sulfamethoxazole

  perphenazine 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 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).

• sunitinib

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

• tacrolimus

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

• telavancin

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

• temazepam

  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.

• terbutaline

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

• tetrabenazine

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

• thioridazine

  perphenazine and thioridazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. 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.

• timolol

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

• tiotropium

  tiotropium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  tiotropium decreases levels of perphenazine by pharmacodynamic antagonism. 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 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.

• topiramate

  perphenazine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

• tramadol

  tramadol and perphenazine 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

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

• triazolam

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

• triclofos

  triclofos and perphenazine 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.

• trihexyphenidyl

  trihexyphenidyl decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  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.

• trimipramine

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

• triprolidine

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

• tropisetron

  perphenazine 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 decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of trospium chloride by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• valbenazine

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

• vecuronium

  vecuronium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  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.

• venlafaxine

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

• 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).

• voriconazole

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

• vorinostat

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

• xylometazoline

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

• yohimbine

  perphenazine 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.

• ziconotide

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

• ziprasidone

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

• zolmitriptan

  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 (78)

• 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.

• 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.

• atropine IV/IM

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

• benazepril

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

• brimonidine

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

• captopril

  perphenazine increases effects of captopril by unspecified interaction mechanism. 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

  perphenazine will increase the level or effect of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. 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.

• darifenacin

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

• 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.

• dexfenfluramine

  perphenazine will increase the level or effect of dexfenfluramine by affecting hepatic enzyme CYP2D6 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.

• ethanol

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

• eucalyptus

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

• fesoterodine

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

• fluphenazine

  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.

• galantamine

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

• haloperidol

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

• 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.

• lisinopril

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

• 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.

• 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.

• metyrapone

  perphenazine 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.

• moexipril

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

• nilotinib

  nilotinib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 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.

• 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.

• parecoxib

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

• 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.

• prochlorperazine

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

• promazine

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

• promethazine

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

• 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.

• 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.

• 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.

• sage

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

• sertraline

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

• thioridazine

  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.

• 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.

• 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.

• tropisetron

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

• abiraterone

  Monitor Closely (1)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.

• abobotulinumtoxinA

  Monitor Closely (1)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

  Monitor Closely (2)aclidinium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of aclidinium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• acrivastine

  Monitor Closely (1)acrivastine and perphenazine both increase sedation. Use Caution/Monitor.

• adagrasib

  Serious - Use Alternative (1)adagrasib, perphenazine. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Each drug prolongs the QTc interval, which may increased the risk of Torsade de pointes, other serious arryhthmias, and sudden death. If coadministration unavoidable, more frequent monitoring is recommended for such patients.

• albiglutide

  Monitor Closely (1)perphenazine, albiglutide. Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase or decrease glucose levels, monitor therapy closely when these agents are concurrently administered.

• albuterol

  Monitor Closely (1)perphenazine increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• alfentanil

  Monitor Closely (1)alfentanil and perphenazine both increase sedation. Use Caution/Monitor.

• alfuzosin

  Monitor Closely (2)perphenazine and alfuzosin both increase QTc interval. Use Caution/Monitor.
  
  alfuzosin and perphenazine both increase QTc interval. Use Caution/Monitor.

• almotriptan

  Monitor Closely (1)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).

• alprazolam

  Monitor Closely (1)alprazolam and perphenazine both increase sedation. Use Caution/Monitor.

• amifampridine

  Monitor Closely (1)perphenazine increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.

• aminolevulinic acid oral

  Serious - Use Alternative (1)aminolevulinic acid oral, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid administering other phototoxic drugs with aminolevulinic acid oral for 24 hr during perioperative period.

• aminolevulinic acid topical

  Serious - Use Alternative (1)perphenazine increases toxicity of aminolevulinic acid topical by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration of photosensitizing drugs may enhance the phototoxic reaction to photodynamic therapy with aminolevulinic acid.

• amiodarone

  Serious - Use Alternative (1)perphenazine and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)amiodarone will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• amisulpride

  Contraindicated (1)amisulpride, perphenazine. Either increases toxicity of the other by Other (see comment). Contraindicated. Comment: Increases risk of neuroleptic malignant syndrome.Serious - Use Alternative (1)perphenazine and amisulpride both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered.

• amitriptyline

  Monitor Closely (1)perphenazine and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)amitriptyline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amitriptyline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• amobarbital

  Monitor Closely (1)amobarbital and perphenazine both increase sedation. Use Caution/Monitor.

• amoxapine

  Monitor Closely (2)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.Serious - Use Alternative (1)perphenazine and amoxapine both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)amoxapine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  amoxapine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• anagrelide

  Monitor Closely (1)anagrelide and perphenazine both increase QTc interval. Use Caution/Monitor.

• anticholinergic/sedative combos

  Monitor Closely (3)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

  Monitor Closely (1)perphenazine and apomorphine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)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

  Monitor Closely (2)arformoterol and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  perphenazine increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• aripiprazole

  Monitor Closely (2)aripiprazole and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  aripiprazole and perphenazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)aripiprazole and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)perphenazine will increase the level or effect of aripiprazole by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• armodafinil

  Monitor Closely (1)perphenazine increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• arsenic trioxide

  Serious - Use Alternative (1)perphenazine and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.

• artemether

  Monitor Closely (1)artemether and perphenazine both increase QTc interval. Use Caution/Monitor.

• artemether/lumefantrine

  Monitor Closely (1)artemether/lumefantrine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

• asenapine

  Monitor Closely (2)asenapine and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  asenapine and perphenazine both increase sedation. Use Caution/Monitor.Minor (1)asenapine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• asenapine transdermal

  Monitor Closely (2)asenapine transdermal and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  asenapine transdermal and perphenazine both increase sedation. Use Caution/Monitor.

• atomoxetine

  Monitor Closely (2)atomoxetine and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  perphenazine will increase the level or effect of atomoxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• atracurium

  Monitor Closely (3)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.
  
  perphenazine increases effects of atracurium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• atropine

  Monitor Closely (3)atropine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  atropine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.Minor (1)perphenazine increases toxicity of atropine by unknown mechanism. Minor/Significance Unknown.

• atropine IV/IM

  Monitor Closely (3)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 inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  atropine IV/IM decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.Minor (1)perphenazine increases toxicity of atropine IV/IM by unknown mechanism. Minor/Significance Unknown.

• avapritinib

  Monitor Closely (1)avapritinib and perphenazine both increase sedation. Use Caution/Monitor.

• azelastine

  Monitor Closely (1)azelastine and perphenazine both increase sedation. Use Caution/Monitor.

• azithromycin

  Monitor Closely (1)perphenazine and azithromycin both increase QTc interval. Use Caution/Monitor.

• baclofen

  Monitor Closely (1)baclofen and perphenazine both increase sedation. Use Caution/Monitor.

• bedaquiline

  Monitor Closely (1)perphenazine and bedaquiline both increase QTc interval. Modify Therapy/Monitor Closely. ECG should be monitored closely

• belladonna alkaloids

  Monitor Closely (3)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.
  
  perphenazine increases effects of belladonna alkaloids by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• belladonna and opium

  Monitor Closely (4)belladonna and opium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  belladonna and opium decreases levels of perphenazine by pharmacodynamic antagonism. 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 perphenazine both increase sedation. Use Caution/Monitor.

• benazepril

  Minor (1)perphenazine increases effects of benazepril by unspecified interaction mechanism. Minor/Significance Unknown.

• benperidol

  Monitor Closely (2)benperidol and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  benperidol and perphenazine both increase sedation. Use Caution/Monitor.

• benzhydrocodone/acetaminophen

  Monitor Closely (2)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.
  
  benzhydrocodone/acetaminophen and perphenazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)benzhydrocodone/acetaminophen, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

• benzphetamine

  Monitor Closely (2)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.

• benztropine

  Monitor Closely (1)perphenazine increases effects of benztropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic adverse effects may be seen with concurrent use. .

• brexanolone

  Monitor Closely (1)brexanolone, perphenazine. Either increases toxicity of the other by sedation. Use Caution/Monitor.

• brexpiprazole

  Monitor Closely (1)brexpiprazole and perphenazine both increase sedation. Use Caution/Monitor.

• brimonidine

  Monitor Closely (1)brimonidine and perphenazine both increase sedation. Use Caution/Monitor.Minor (1)brimonidine increases effects of perphenazine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

• brivaracetam

  Monitor Closely (1)brivaracetam and perphenazine both increase sedation. Use Caution/Monitor.

• bromocriptine

  Serious - Use Alternative (1)perphenazine decreases effects of bromocriptine by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

• brompheniramine

  Monitor Closely (1)brompheniramine and perphenazine both increase sedation. Use Caution/Monitor.

• buprenorphine

  Monitor Closely (2)buprenorphine and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  buprenorphine and perphenazine both increase sedation. Use Caution/Monitor.

• buprenorphine buccal

  Monitor Closely (2)buprenorphine buccal and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  buprenorphine buccal and perphenazine both increase sedation. Use Caution/Monitor.

• buprenorphine subdermal implant

  Monitor Closely (2)buprenorphine subdermal implant and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  buprenorphine subdermal implant and perphenazine both increase sedation. Use Caution/Monitor.

• buprenorphine transdermal

  Monitor Closely (2)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

  Monitor Closely (2)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.

• bupropion

  Monitor Closely (2)perphenazine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.
  
  bupropion will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• butabarbital

  Monitor Closely (1)butabarbital and perphenazine both increase sedation. Use Caution/Monitor.

• butalbital

  Monitor Closely (1)butalbital and perphenazine both increase sedation. Use Caution/Monitor.

• butorphanol

  Monitor Closely (1)butorphanol and perphenazine both increase sedation. Use Caution/Monitor.

• cabergoline

  Serious - Use Alternative (1)perphenazine decreases effects of cabergoline by pharmacodynamic antagonism. Contraindicated.

• caffeine

  Monitor Closely (1)perphenazine increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• calcium/magnesium/potassium/sodium oxybates

  Serious - Use Alternative (1)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.

• captopril

  Minor (1)perphenazine increases effects of captopril by unspecified interaction mechanism. Minor/Significance Unknown.

• carbinoxamine

  Monitor Closely (1)carbinoxamine and perphenazine both increase sedation. Use Caution/Monitor.

• carisoprodol

  Monitor Closely (1)carisoprodol and perphenazine both increase sedation. Use Caution/Monitor.

• carvedilol

  Monitor Closely (1)perphenazine will increase the level or effect of carvedilol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• celecoxib

  Minor (1)celecoxib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• cenobamate

  Monitor Closely (1)cenobamate, perphenazine. Either increases effects of the other by sedation. Use Caution/Monitor.

• ceritinib

  Monitor Closely (1)ceritinib and perphenazine both increase QTc interval. Use Caution/Monitor.

• chasteberry

  Minor (1)chasteberry decreases effects of perphenazine by pharmacodynamic antagonism. Minor/Significance Unknown. (Theoretical interaction).

• chloral hydrate

  Monitor Closely (1)chloral hydrate and perphenazine both increase sedation. Use Caution/Monitor.

• chlordiazepoxide

  Monitor Closely (1)chlordiazepoxide and perphenazine both increase sedation. Use Caution/Monitor.

• chloroquine

  Minor (3)chloroquine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  chloroquine increases levels of perphenazine by decreasing metabolism. Minor/Significance Unknown.
  
  chloroquine increases toxicity of perphenazine by QTc interval. Minor/Significance Unknown.

• chlorpheniramine

  Monitor Closely (1)chlorpheniramine and perphenazine both increase sedation. Use Caution/Monitor.

• chlorpromazine

  Monitor Closely (2)chlorpromazine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  chlorpromazine and perphenazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)chlorpromazine and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)perphenazine will increase the level or effect of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• chlorzoxazone

  Monitor Closely (1)chlorzoxazone and perphenazine both increase sedation. Use Caution/Monitor.

• cigarette smoking

  Monitor Closely (1)cigarette smoking decreases levels of perphenazine by increasing metabolism. Use Caution/Monitor. Interaction mainly seen w/chlorpromazine & thioridazine, but may occur w/other phenothiazines.

• cimetidine

  Minor (1)cimetidine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• cinnarizine

  Monitor Closely (1)cinnarizine and perphenazine both increase sedation. Use Caution/Monitor.

• cisatracurium

  Monitor Closely (3)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.

• citalopram

  Monitor Closely (1)citalopram and perphenazine both increase QTc interval. Use Caution/Monitor.

• clarithromycin

  Serious - Use Alternative (1)perphenazine and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug.

• clemastine

  Monitor Closely (1)clemastine and perphenazine both increase sedation. Use Caution/Monitor.

• clobazam

  Monitor Closely (1)clobazam will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly.

• clomipramine

  Monitor Closely (2)perphenazine will increase the level or effect of clomipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  perphenazine and clomipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and clomipramine both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)clomipramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  clomipramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• clonazepam

  Monitor Closely (1)clonazepam and perphenazine both increase sedation. Use Caution/Monitor.

• clonidine

  Monitor Closely (1)clonidine, perphenazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• clorazepate

  Monitor Closely (1)clorazepate and perphenazine both increase sedation. Use Caution/Monitor.

• clozapine

  Monitor Closely (3)clozapine and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  clozapine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  clozapine and perphenazine both increase sedation. Use Caution/Monitor.

• cobicistat

  Monitor Closely (1)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.

• codeine

  Monitor Closely (1)codeine and perphenazine both increase sedation. Use Caution/Monitor.Minor (2)perphenazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.
  
  perphenazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

• crizotinib

  Monitor Closely (1)crizotinib and perphenazine both increase QTc interval. Use Caution/Monitor.

• cyclizine

  Monitor Closely (4)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.
  
  perphenazine increases effects of cyclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  cyclizine and perphenazine both increase sedation. Use Caution/Monitor.

• cyclobenzaprine

  Monitor Closely (4)cyclobenzaprine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  cyclobenzaprine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of cyclobenzaprine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  cyclobenzaprine and perphenazine both increase sedation. Use Caution/Monitor.

• cyproheptadine

  Monitor Closely (1)cyproheptadine and perphenazine both increase sedation. Use Caution/Monitor.

• dacomitinib

  Serious - Use Alternative (1)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.

• dantrolene

  Monitor Closely (1)dantrolene and perphenazine both increase sedation. Use Caution/Monitor.

• daridorexant

  Monitor Closely (1)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.

• darifenacin

  Monitor Closely (3)darifenacin decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  darifenacin decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of darifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.Minor (1)darifenacin will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dasatinib

  Monitor Closely (1)perphenazine and dasatinib both increase QTc interval. Modify Therapy/Monitor Closely.

• degarelix

  Serious - Use Alternative (1)degarelix and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.

• desflurane

  Monitor Closely (2)desflurane and perphenazine both increase QTc interval. Use Caution/Monitor.
  
  desflurane and perphenazine both increase sedation. Use Caution/Monitor.

• desipramine

  Monitor Closely (2)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.Serious - Use Alternative (1)perphenazine and desipramine both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)desipramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  desipramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• desvenlafaxine

  Monitor Closely (1)desvenlafaxine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

• deutetrabenazine

  Monitor Closely (3)perphenazine and deutetrabenazine both increase sedation. Use Caution/Monitor.
  
  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.
  
  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

  Monitor Closely (1)dexchlorpheniramine and perphenazine both increase sedation. Use Caution/Monitor.

• dexfenfluramine

  Monitor Closely (2)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.
  
  perphenazine increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)perphenazine will increase the level or effect of dexfenfluramine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dexmedetomidine

  Monitor Closely (1)dexmedetomidine and perphenazine both increase sedation. Use Caution/Monitor.

• dexmethylphenidate

  Monitor Closely (2)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.
  
  perphenazine increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dextroamphetamine

  Monitor Closely (2)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.
  
  perphenazine increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)perphenazine will increase the level or effect of dextroamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dextroamphetamine transdermal

  Monitor Closely (1)perphenazine, dextroamphetamine transdermal. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue dextroamphetamine transdermal and concomitant serotonergic drug(s).

• dextromethorphan

  Monitor Closely (1)dextromethorphan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).Minor (1)perphenazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• dextromoramide

  Monitor Closely (1)dextromoramide and perphenazine both increase sedation. Use Caution/Monitor.

• diamorphine

  Monitor Closely (1)diamorphine and perphenazine both increase sedation. Use Caution/Monitor.

• diazepam

  Monitor Closely (1)diazepam and perphenazine both increase sedation. Use Caution/Monitor.

• dicyclomine

  Monitor Closely (3)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.

• diethylpropion

  Monitor Closely (2)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.

• difelikefalin

  Monitor Closely (1)difelikefalin and perphenazine both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  Monitor Closely (1)difenoxin hcl and perphenazine both increase sedation. Use Caution/Monitor.

• dihydroergotamine

  Monitor Closely (1)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).

• dimenhydrinate

  Monitor Closely (1)dimenhydrinate and perphenazine both increase sedation. Use Caution/Monitor.

• diphenhydramine

  Monitor Closely (4)diphenhydramine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  diphenhydramine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of diphenhydramine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  diphenhydramine and perphenazine both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• diphenoxylate hcl

  Monitor Closely (1)diphenoxylate hcl and perphenazine both increase sedation. Use Caution/Monitor.

• dipipanone

  Monitor Closely (1)dipipanone and perphenazine both increase sedation. Use Caution/Monitor.

• disopyramide

  Contraindicated (1)perphenazine and disopyramide both increase QTc interval. Contraindicated.

• dobutamine

  Monitor Closely (2)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.

• dofetilide

  Monitor Closely (1)dofetilide increases toxicity of perphenazine by QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.

• dolasetron

  Monitor Closely (1)perphenazine and dolasetron both increase QTc interval. Modify Therapy/Monitor Closely.

• donepezil

  Monitor Closely (1)donepezil and perphenazine both increase QTc interval. Use Caution/Monitor.Minor (1)perphenazine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• donepezil transdermal

  Monitor Closely (1)donepezil transdermal, perphenazine. Either decreases effects of the other by pharmacodynamic antagonism. Use Caution/Monitor.

• dopamine

  Monitor Closely (2)perphenazine, dopamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine decreases effects of dopamine by pharmacodynamic antagonism. Contraindicated.

• dopexamine

  Monitor Closely (1)perphenazine increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dosulepin

  Monitor Closely (1)perphenazine and dosulepin both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and dosulepin both increase QTc interval. Avoid or Use Alternate Drug.

• doxepin

  Monitor Closely (1)perphenazine and doxepin both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and doxepin both increase QTc interval. Avoid or Use Alternate Drug.Minor (3)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.

• doxylamine

  Monitor Closely (1)doxylamine and perphenazine both increase sedation. Use Caution/Monitor.

• dronedarone

  Serious - Use Alternative (1)perphenazine and dronedarone both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)dronedarone will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• droperidol

  Monitor Closely (2)droperidol and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  droperidol and perphenazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and droperidol both increase QTc interval. Avoid or Use Alternate Drug.

• duloxetine

  Monitor Closely (1)perphenazine will increase the level or effect of duloxetine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Minor (1)duloxetine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• efavirenz

  Monitor Closely (1)efavirenz and perphenazine both increase QTc interval. Use Caution/Monitor.

• eletriptan

  Monitor Closely (1)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).

• eliglustat

  Monitor Closely (2)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.
  
  eliglustat and perphenazine both increase QTc interval. Use Caution/Monitor.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (1)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.

• enalapril

  Minor (1)perphenazine increases effects of enalapril by unspecified interaction mechanism. Minor/Significance Unknown.

• encainide

  Minor (1)perphenazine will increase the level or effect of encainide by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• encorafenib

  Monitor Closely (1)encorafenib and perphenazine both increase QTc interval. Use Caution/Monitor.

• entrectinib

  Monitor Closely (1)entrectinib and perphenazine both increase QTc interval. Use Caution/Monitor.

• ephedrine

  Monitor Closely (2)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.

• epinephrine

  Monitor Closely (3)perphenazine, epinephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine 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.Serious - Use Alternative (1)epinephrine and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.

• epinephrine racemic

  Monitor Closely (2)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.
  
  perphenazine increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)epinephrine racemic and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.

• ergoloid mesylates

  Monitor Closely (1)ergoloid mesylates, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• ergotamine

  Monitor Closely (1)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).

• eribulin

  Monitor Closely (1)eribulin and perphenazine both increase QTc interval. Use Caution/Monitor.

• erythromycin base

  Serious - Use Alternative (1)perphenazine and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  Serious - Use Alternative (1)perphenazine and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  Serious - Use Alternative (1)perphenazine and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin stearate

  Serious - Use Alternative (1)perphenazine and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.

• escitalopram

  Monitor Closely (1)escitalopram increases toxicity of perphenazine by QTc interval. Use Caution/Monitor.

• estazolam

  Monitor Closely (1)estazolam and perphenazine both increase sedation. Use Caution/Monitor.

• ethanol

  Monitor Closely (1)perphenazine and ethanol both increase sedation. Use Caution/Monitor.Minor (1)ethanol, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.

• etomidate

  Monitor Closely (1)etomidate and perphenazine both increase sedation. Use Caution/Monitor.

• eucalyptus

  Minor (1)perphenazine and eucalyptus both increase sedation. Minor/Significance Unknown.

• fedratinib

  Monitor Closely (1)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.

• fenfluramine

  Monitor Closely (2)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.
  
  perphenazine increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• fentanyl

  Monitor Closely (1)fentanyl, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).Serious - Use Alternative (1)fentanyl, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl intranasal

  Serious - Use Alternative (1)fentanyl intranasal, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl transdermal

  Serious - Use Alternative (1)fentanyl transdermal, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fentanyl transmucosal

  Serious - Use Alternative (1)fentanyl transmucosal, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration with other CNS depressants, such as skeletal muscle relaxants, may cause respiratory depression, hypotension, profound sedation, coma, and/or death. Consider dose reduction of either or both agents to avoid serious adverse effects. Monitor for hypotension, respiratory depression, and profound sedation.

• fesoterodine

  Monitor Closely (3)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.Minor (1)perphenazine will increase the level or effect of fesoterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• fezolinetant

  Contraindicated (1)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

• fingolimod

  Monitor Closely (1)fingolimod and perphenazine both increase QTc interval. Use Caution/Monitor.

• flavoxate

  Monitor Closely (3)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.
  
  perphenazine increases effects of flavoxate by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• flecainide

  Monitor Closely (2)perphenazine will increase the level or effect of flecainide by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  perphenazine and flecainide both increase QTc interval. Modify Therapy/Monitor Closely.

• flibanserin

  Monitor Closely (1)flibanserin, perphenazine. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• fluconazole

  Serious - Use Alternative (1)perphenazine and fluconazole both increase QTc interval. Avoid or Use Alternate Drug.

• fluoxetine

  Serious - Use Alternative (3)perphenazine and fluoxetine both increase QTc interval. 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.
  
  perphenazine will increase the level or effect of fluoxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• fluphenazine

  Monitor Closely (2)fluphenazine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  fluphenazine and perphenazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fluphenazine and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)perphenazine will increase the level or effect of fluphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• flurazepam

  Monitor Closely (1)flurazepam and perphenazine both increase sedation. Use Caution/Monitor.

• fluvoxamine

  Monitor Closely (1)fluvoxamine and perphenazine both increase QTc interval. Use Caution/Monitor.

• formoterol

  Monitor Closely (1)perphenazine increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and formoterol both increase QTc interval. Avoid or Use Alternate Drug.

• foscarnet

  Monitor Closely (1)perphenazine and foscarnet both increase QTc interval. Modify Therapy/Monitor Closely.

• fosinopril

  Minor (1)perphenazine increases effects of fosinopril by unspecified interaction mechanism. Minor/Significance Unknown.

• frovatriptan

  Monitor Closely (1)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).

• galantamine

  Minor (1)perphenazine will increase the level or effect of galantamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• ganaxolone

  Monitor Closely (1)perphenazine and ganaxolone both increase sedation. Use Caution/Monitor.

• gemifloxacin

  Monitor Closely (1)gemifloxacin and perphenazine both increase QTc interval. Use Caution/Monitor.

• gilteritinib

  Monitor Closely (1)gilteritinib and perphenazine both increase QTc interval. Use Caution/Monitor.

• givosiran

  Serious - Use Alternative (1)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.

• glycopyrrolate

  Monitor Closely (2)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 inhaled

  Monitor Closely (4)glycopyrrolate inhaled decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. 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.
  
  perphenazine increases toxicity of glycopyrrolate inhaled by unknown mechanism. Use Caution/Monitor.

• glycopyrronium tosylate topical

  Monitor Closely (1)glycopyrronium tosylate topical, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of glycopyrronium tosylate topical with other anticholinergic medications may result in additive anticholinergic adverse effects.

• granisetron

  Monitor Closely (1)granisetron and perphenazine both increase QTc interval. Use Caution/Monitor.

• guanfacine

  Monitor Closely (1)guanfacine, perphenazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Additive hypotensive effects; potential delirium.

• haloperidol

  Monitor Closely (3)perphenazine will increase the level or effect of haloperidol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  haloperidol and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  haloperidol and perphenazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and haloperidol both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)haloperidol will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• henbane

  Monitor Closely (3)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.
  
  perphenazine increases effects of henbane by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• homatropine

  Monitor Closely (3)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.

• hydrocodone

  Monitor Closely (1)perphenazine will increase the level or effect of hydrocodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Hydromorphone (<3% of the circulating parent hydrocodone) is mainly formed by CYP2D6 mediated O-demethylation of hydrocodone. Hydromorphone may contribute to the total analgesic effect of hydrocodone.Serious - Use Alternative (1)hydrocodone, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

• hydromorphone

  Monitor Closely (2)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.

• hydroxychloroquine sulfate

  Serious - Use Alternative (1)hydroxychloroquine sulfate and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.

• hydroxyzine

  Monitor Closely (2)hydroxyzine and perphenazine both increase sedation. Use Caution/Monitor.
  
  hydroxyzine and perphenazine both increase QTc interval. Use Caution/Monitor.

• hyoscyamine

  Monitor Closely (3)hyoscyamine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  hyoscyamine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of hyoscyamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• hyoscyamine spray

  Monitor Closely (3)perphenazine increases effects of hyoscyamine spray by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.
  
  hyoscyamine spray decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  hyoscyamine spray decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

• ibutilide

  Contraindicated (1)perphenazine and ibutilide both increase QTc interval. Contraindicated.

• iloperidone

  Monitor Closely (4)perphenazine will increase the level or effect of iloperidone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  perphenazine 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 perphenazine both increase sedation. Use Caution/Monitor.

• imatinib

  Minor (1)imatinib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• imidapril

  Minor (1)perphenazine increases effects of imidapril by unspecified interaction mechanism. Minor/Significance Unknown.

• imipramine

  Monitor Closely (2)perphenazine will increase the level or effect of imipramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  perphenazine and imipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and imipramine both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)imipramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  imipramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• incobotulinumtoxinA

  Monitor Closely (1)perphenazine, incobotulinumtoxinA. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects.

• indacaterol, inhaled

  Monitor Closely (1)indacaterol, inhaled, perphenazine. QTc interval. Use Caution/Monitor. Drugs that are known to prolong the QTc interval may have an increased the risk of ventricular arrhythmias.

• indapamide

  Contraindicated (1)perphenazine and indapamide both increase QTc interval. Contraindicated.

• insulin degludec

  Monitor Closely (1)perphenazine decreases effects of insulin degludec by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

• insulin degludec/insulin aspart

  Monitor Closely (1)perphenazine decreases effects of insulin degludec/insulin aspart by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

• insulin inhaled

  Monitor Closely (1)perphenazine decreases effects of insulin inhaled by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.

• ipratropium

  Monitor Closely (3)ipratropium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  ipratropium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of ipratropium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• isocarboxazid

  Serious - Use Alternative (1)isocarboxazid, perphenazine. Other (see comment). Contraindicated. Comment: Concurrent use may prolong or intensify the hypotensive, anticholinergic, or sedative effects of isocarboxazid or perphenazine.

• isoflurane

  Monitor Closely (1)isoflurane and perphenazine both increase QTc interval. Use Caution/Monitor.

• isoproterenol

  Monitor Closely (2)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.
  
  perphenazine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• itraconazole

  Serious - Use Alternative (1)perphenazine and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

• ivosidenib

  Serious - Use Alternative (1)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.

• ketamine

  Monitor Closely (1)ketamine and perphenazine both increase sedation. Use Caution/Monitor.

• ketoconazole

  Serious - Use Alternative (1)perphenazine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• ketotifen, ophthalmic

  Monitor Closely (1)perphenazine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

• lapatinib

  Monitor Closely (1)perphenazine and lapatinib both increase QTc interval. Modify Therapy/Monitor Closely.

• lasmiditan

  Monitor Closely (1)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.

• lemborexant

  Monitor Closely (1)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.

• levalbuterol

  Monitor Closely (1)perphenazine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• levodopa

  Serious - Use Alternative (1)perphenazine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.

• levodopa inhaled

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

• levofloxacin

  Monitor Closely (1)perphenazine and levofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

• levoketoconazole

  Serious - Use Alternative (1)perphenazine and levoketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• levomilnacipran

  Monitor Closely (1)levomilnacipran, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• levorphanol

  Monitor Closely (1)levorphanol and perphenazine both increase sedation. Use Caution/Monitor.

• linezolid

  Monitor Closely (1)linezolid, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• liraglutide

  Monitor Closely (1)perphenazine, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase or decrease glucose levels, monitor therapy closely when these agents are concurrently administered.

• lisdexamfetamine

  Monitor Closely (2)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.

• lisinopril

  Minor (1)perphenazine increases effects of lisinopril by unspecified interaction mechanism. Minor/Significance Unknown.

• lisuride

  Serious - Use Alternative (1)perphenazine decreases effects of lisuride by pharmacodynamic antagonism. Contraindicated.

• lithium

  Monitor Closely (3)lithium, perphenazine. Other (see comment). Use Caution/Monitor. Comment: Risk of neurotoxicity. Multiple mechanisms involved.
  
  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).
  
  lithium and perphenazine both increase QTc interval. Use Caution/Monitor.

• lofepramine

  Monitor Closely (2)perphenazine will increase the level or effect of lofepramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  perphenazine and lofepramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and lofepramine both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)lofepramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  lofepramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• lofexidine

  Monitor Closely (1)perphenazine and lofexidine both increase sedation. Use Caution/Monitor.

• loprazolam

  Monitor Closely (1)loprazolam and perphenazine both increase sedation. Use Caution/Monitor.

• loratadine

  Minor (1)perphenazine will increase the level or effect of loratadine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• lorazepam

  Monitor Closely (1)lorazepam and perphenazine both increase sedation. Use Caution/Monitor.

• lorcaserin

  Monitor Closely (2)lorcaserin will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  lorcaserin, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).Serious - Use Alternative (1)perphenazine and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.

• lormetazepam

  Monitor Closely (1)lormetazepam and perphenazine both increase sedation. Use Caution/Monitor.

• loxapine

  Monitor Closely (2)loxapine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  loxapine and perphenazine both increase sedation. Use Caution/Monitor.

• loxapine inhaled

  Monitor Closely (2)loxapine inhaled and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  loxapine inhaled and perphenazine both increase sedation. Use Caution/Monitor.

• lumefantrine

  Monitor Closely (1)lumefantrine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

• lurasidone

  Monitor Closely (1)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.

• macimorelin

  Serious - Use Alternative (1)macimorelin and perphenazine both increase QTc interval. Avoid or Use Alternate Drug. Macimorelin causes an increase of ~11 msec in the corrected QT interval. Avoid coadministration with drugs that prolong QT interval, which could increase risk for developing torsade de pointes-type ventricular tachycardia. Allow sufficient washout time of drugs that are known to prolong the QT interval before administering macimorelin.

• maprotiline

  Monitor Closely (1)perphenazine and maprotiline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and maprotiline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)maprotiline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  maprotiline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• maraviroc

  Minor (1)maraviroc will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• marijuana

  Monitor Closely (1)perphenazine and marijuana both increase sedation. Use Caution/Monitor.Minor (1)marijuana will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• meclizine

  Monitor Closely (3)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.

• melatonin

  Monitor Closely (1)perphenazine and melatonin both increase sedation. Use Caution/Monitor.

• meperidine

  Monitor Closely (2)meperidine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  meperidine and perphenazine both increase sedation. Use Caution/Monitor.

• meprobamate

  Monitor Closely (1)perphenazine and meprobamate both increase sedation. Use Caution/Monitor.

• metaproterenol

  Monitor Closely (1)perphenazine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• metaxalone

  Monitor Closely (1)metaxalone and perphenazine both increase sedation. Use Caution/Monitor.

• metformin

  Monitor Closely (1)perphenazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.

• methadone

  Monitor Closely (3)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).
  
  perphenazine and methadone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  methadone and perphenazine both increase sedation. Use Caution/Monitor.

• methamphetamine

  Monitor Closely (3)perphenazine will increase the level or effect of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  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.

• methocarbamol

  Monitor Closely (1)methocarbamol and perphenazine both increase sedation. Use Caution/Monitor.

• methoxsalen

  Monitor Closely (1)methoxsalen, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive photosensitizing effects.

• methscopolamine

  Monitor Closely (3)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.

• methyl aminolevulinate

  Serious - Use Alternative (1)perphenazine, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.

• methyldopa

  Serious - Use Alternative (1)perphenazine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

• methylenedioxymethamphetamine

  Monitor Closely (2)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.

• methylergonovine

  Monitor Closely (1)methylergonovine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• methylphenidate

  Monitor Closely (2)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.

• metoclopramide

  Monitor Closely (1)perphenazine and metoclopramide both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

• metoclopramide intranasal

  Serious - Use Alternative (2)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.

• metoprolol

  Monitor Closely (1)perphenazine will increase the level or effect of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• metrizamide

  Contraindicated (1)perphenazine, metrizamide. Mechanism: unknown. Contraindicated. Risk of seizure. D/C phenothiazine 24h before admin. of metrizamide.

• metyrapone

  Minor (1)perphenazine decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown.

• metyrosine

  Minor (1)metyrosine increases toxicity of perphenazine by pharmacodynamic synergism. Minor/Significance Unknown. Increased extrapyramidal symptoms.

• mexiletine

  Monitor Closely (1)perphenazine will increase the level or effect of mexiletine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• midazolam

  Monitor Closely (1)midazolam and perphenazine both increase sedation. Use Caution/Monitor.

• midazolam intranasal

  Monitor Closely (1)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.

• midodrine

  Monitor Closely (2)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.

• mifepristone

  Monitor Closely (1)mifepristone, perphenazine. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.

• milnacipran

  Monitor Closely (1)milnacipran, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• mirabegron

  Monitor Closely (1)mirabegron will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• mirtazapine

  Monitor Closely (2)perphenazine and mirtazapine both increase sedation. Use Caution/Monitor.
  
  mirtazapine and perphenazine both increase QTc interval. Use Caution/Monitor.

• mobocertinib

  Serious - Use Alternative (1)mobocertinib and perphenazine both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.

• modafinil

  Monitor Closely (1)perphenazine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• moexipril

  Minor (1)perphenazine increases effects of moexipril by unspecified interaction mechanism. Minor/Significance Unknown.

• morphine

  Monitor Closely (2)perphenazine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  morphine and perphenazine both increase sedation. Use Caution/Monitor.

• motherwort

  Monitor Closely (1)perphenazine and motherwort both increase sedation. Use Caution/Monitor.

• moxifloxacin

  Serious - Use Alternative (1)perphenazine and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• moxonidine

  Monitor Closely (1)perphenazine and moxonidine both increase sedation. Use Caution/Monitor.

• nabilone

  Monitor Closely (1)perphenazine and nabilone both increase sedation. Use Caution/Monitor.

• nalbuphine

  Monitor Closely (1)nalbuphine and perphenazine both increase sedation. Use Caution/Monitor.

• naratriptan

  Monitor Closely (1)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

  Monitor Closely (1)perphenazine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• nilotinib

  Serious - Use Alternative (1)perphenazine and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)nilotinib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• norepinephrine

  Monitor Closely (2)perphenazine, norepinephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• nortriptyline

  Monitor Closely (2)perphenazine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  perphenazine and nortriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)nortriptyline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  nortriptyline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• octreotide

  Serious - Use Alternative (1)perphenazine and octreotide both increase QTc interval. Avoid or Use Alternate Drug.

• octreotide (Antidote)

  Serious - Use Alternative (1)perphenazine and octreotide (Antidote) both increase QTc interval. Avoid or Use Alternate Drug.

• ofloxacin

  Monitor Closely (1)perphenazine and ofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

• olanzapine

  Monitor Closely (3)olanzapine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  olanzapine and perphenazine both increase sedation. Use Caution/Monitor.
  
  olanzapine and perphenazine both increase QTc interval. Use Caution/Monitor.

• oliceridine

  Monitor Closely (1)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).

• olodaterol inhaled

  Monitor Closely (1)perphenazine and olodaterol inhaled both increase QTc interval. Use Caution/Monitor. Drugs that prolong the QTc interval and may potentiate the effects of beta2 agonists on the cardiovascular system; increased risk of ventricular arrhythmias

• olopatadine intranasal

  Serious - Use Alternative (1)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.

• onabotulinumtoxinA

  Monitor Closely (3)onabotulinumtoxinA decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  onabotulinumtoxinA decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of onabotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• ondansetron

  Serious - Use Alternative (1)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.

• opium tincture

  Monitor Closely (1)opium tincture and perphenazine both increase sedation. Use Caution/Monitor.

• orphenadrine

  Monitor Closely (1)orphenadrine and perphenazine both increase sedation. Use Caution/Monitor.

• osimertinib

  Monitor Closely (1)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.

• oxaliplatin

  Monitor Closely (1)oxaliplatin and perphenazine both increase QTc interval. Use Caution/Monitor.

• oxazepam

  Monitor Closely (1)oxazepam and perphenazine both increase sedation. Use Caution/Monitor.

• oxybutynin

  Monitor Closely (3)oxybutynin decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  oxybutynin decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of oxybutynin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.Minor (1)oxybutynin increases toxicity of perphenazine by unspecified interaction mechanism. Minor/Significance Unknown.

• oxybutynin topical

  Monitor Closely (3)oxybutynin topical decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  oxybutynin topical decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of oxybutynin topical by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.Minor (1)oxybutynin topical increases toxicity of perphenazine by unspecified interaction mechanism. Minor/Significance Unknown.

• oxybutynin transdermal

  Monitor Closely (3)oxybutynin transdermal decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  oxybutynin transdermal decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of oxybutynin transdermal by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.Minor (1)oxybutynin transdermal increases toxicity of perphenazine by unspecified interaction mechanism. Minor/Significance Unknown.

• oxycodone

  Monitor Closely (2)perphenazine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  oxycodone and perphenazine both increase sedation. Use Caution/Monitor.Minor (1)perphenazine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

• oxymorphone

  Monitor Closely (2)perphenazine will increase the level or effect of oxymorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  oxymorphone and perphenazine both increase sedation. Use Caution/Monitor.

• ozanimod

  Monitor Closely (1)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.

• paliperidone

  Monitor Closely (3)perphenazine and paliperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  paliperidone and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  paliperidone and perphenazine both increase sedation. Use Caution/Monitor.

• pancuronium

  Monitor Closely (3)pancuronium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  pancuronium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of pancuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• panobinostat

  Monitor Closely (1)panobinostat will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Panobinostat can increase the levels and effects of sensitive CYP2D6 substrates or those with a narrow therapeutic index CYP2D6.

• papaveretum

  Monitor Closely (1)papaveretum and perphenazine both increase sedation. Use Caution/Monitor.

• papaverine

  Monitor Closely (1)perphenazine and papaverine both increase sedation. Use Caution/Monitor.

• parecoxib

  Minor (1)parecoxib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• paroxetine

  Monitor Closely (1)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).Serious - Use Alternative (3)perphenazine and paroxetine both increase QTc interval. Avoid or Use Alternate Drug.
  
  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.

• pasireotide

  Monitor Closely (1)perphenazine and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.

• pazopanib

  Monitor Closely (1)perphenazine and pazopanib both increase QTc interval. Use Caution/Monitor.

• peginterferon alfa 2b

  Monitor Closely (1)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.

• pentamidine

  Contraindicated (1)perphenazine and pentamidine both increase QTc interval. Contraindicated.

• pentazocine

  Monitor Closely (1)pentazocine and perphenazine both increase sedation. Use Caution/Monitor.

• pentobarbital

  Monitor Closely (1)pentobarbital and perphenazine both increase sedation. Use Caution/Monitor.

• perhexiline

  Minor (1)perphenazine will increase the level or effect of perhexiline by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• perindopril

  Minor (1)perphenazine increases effects of perindopril by unspecified interaction mechanism. Minor/Significance Unknown.

• phendimetrazine

  Monitor Closely (2)perphenazine, phendimetrazine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.
  
  perphenazine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenelzine

  Monitor Closely (1)phenelzine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• phenobarbital

  Monitor Closely (1)phenobarbital and perphenazine both increase sedation. Use Caution/Monitor.

• phentermine

  Monitor Closely (2)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.
  
  perphenazine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenylephrine

  Monitor Closely (2)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.
  
  perphenazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• phenylephrine PO

  Monitor Closely (2)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.
  
  perphenazine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

• pholcodine

  Monitor Closely (1)perphenazine and pholcodine both increase sedation. Use Caution/Monitor.

• pimozide

  Contraindicated (1)perphenazine and pimozide both increase QTc interval. Contraindicated.Monitor Closely (2)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.

• pirbuterol

  Monitor Closely (1)perphenazine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• porfimer

  Monitor Closely (1)perphenazine, porfimer. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced photosensitivity.

• posaconazole

  Monitor Closely (1)perphenazine and posaconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• pralidoxime

  Monitor Closely (3)pralidoxime decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  pralidoxime decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of pralidoxime by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• pramipexole

  Serious - Use Alternative (1)perphenazine decreases effects of pramipexole by pharmacodynamic antagonism. Contraindicated.

• primaquine

  Monitor Closely (1)primaquine and perphenazine both increase QTc interval. Use Caution/Monitor.

• primidone

  Monitor Closely (1)primidone and perphenazine both increase sedation. Use Caution/Monitor.

• procainamide

  Contraindicated (1)perphenazine and procainamide both increase QTc interval. Contraindicated.

• procarbazine

  Monitor Closely (2)procarbazine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).
  
  procarbazine, perphenazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Excessive sedation.

• prochlorperazine

  Monitor Closely (2)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.Serious - Use Alternative (1)perphenazine and prochlorperazine both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)perphenazine will increase the level or effect of prochlorperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• promazine

  Serious - Use Alternative (1)perphenazine and promazine both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)perphenazine will increase the level or effect of promazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• promethazine

  Monitor Closely (3)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.Serious - Use Alternative (1)perphenazine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)perphenazine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• propafenone

  Monitor Closely (2)perphenazine will increase the level or effect of propafenone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  propafenone will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• propantheline

  Monitor Closely (3)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

  Monitor Closely (1)propofol and perphenazine both increase sedation. Use Caution/Monitor.

• propranolol

  Monitor Closely (1)perphenazine will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• propylhexedrine

  Monitor Closely (2)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.
  
  perphenazine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• protriptyline

  Monitor Closely (1)perphenazine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)protriptyline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  protriptyline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• pseudoephedrine

  Monitor Closely (1)perphenazine, pseudoephedrine. Mechanism: unknown. Use Caution/Monitor. Consider avoiding use of pseudoephedrine in patients receiving phenothiazines (especially thioridazine) due to the potential risk of cardiac arrhythmia or sudden death. Monitor for evidence of ventricular arrhythmias during concomitant use.

• pyrimethamine

  Minor (1)pyrimethamine increases levels of perphenazine by decreasing metabolism. Minor/Significance Unknown.

• quazepam

  Monitor Closely (1)quazepam and perphenazine both increase sedation. Use Caution/Monitor.

• quetiapine

  Monitor Closely (2)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.

• quinacrine

  Minor (1)quinacrine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• quinapril

  Minor (1)perphenazine increases effects of quinapril by unspecified interaction mechanism. Minor/Significance Unknown.

• quinidine

  Contraindicated (1)perphenazine and quinidine both increase QTc interval. Contraindicated.Monitor Closely (1)quinidine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)quinidine, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Additive cardiac effects.

• quinine

  Monitor Closely (1)perphenazine and quinine both increase QTc interval. Use Caution/Monitor.

• ramelteon

  Monitor Closely (1)perphenazine and ramelteon both increase sedation. Use Caution/Monitor.

• ramipril

  Minor (1)perphenazine increases effects of ramipril by unspecified interaction mechanism. Minor/Significance Unknown.

• ranolazine

  Monitor Closely (1)perphenazine and ranolazine both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)ranolazine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• rapacuronium

  Monitor Closely (3)rapacuronium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  rapacuronium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of rapacuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• remimazolam

  Monitor Closely (1)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.

• ribociclib

  Serious - Use Alternative (1)ribociclib increases toxicity of perphenazine by QTc interval. Avoid or Use Alternate Drug.

• rimabotulinumtoxinB

  Monitor Closely (1)perphenazine, rimabotulinumtoxinB. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Anticholinergics may enhance botulinum toxin effects. Closely monitor for increased neuromuscular blockade.

• risperidone

  Monitor Closely (3)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.
  
  perphenazine and risperidone both increase sedation. Use Caution/Monitor.Minor (1)perphenazine will increase the level or effect of risperidone by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• ritonavir

  Minor (1)ritonavir will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• rizatriptan

  Monitor Closely (1)rizatriptan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• rocuronium

  Monitor Closely (3)rocuronium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  rocuronium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of rocuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• rolapitant

  Monitor Closely (1)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.

• romidepsin

  Monitor Closely (1)perphenazine and romidepsin both increase QTc interval. Modify Therapy/Monitor Closely.

• ropinirole

  Serious - Use Alternative (1)perphenazine decreases effects of ropinirole by pharmacodynamic antagonism. Contraindicated.

• safinamide

  Serious - Use Alternative (1)perphenazine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.

• sage

  Minor (1)perphenazine and sage both increase sedation. Minor/Significance Unknown.

• salmeterol

  Monitor Closely (1)perphenazine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• saquinavir

  Serious - Use Alternative (1)saquinavir, perphenazine. Either increases toxicity of the other by QTc interval. Avoid or Use Alternate Drug. Increased risk of PR or QT prolongation and cardiac arrhythmias.

• scopolamine

  Monitor Closely (3)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.

• scullcap

  Monitor Closely (1)perphenazine and scullcap both increase sedation. Use Caution/Monitor.

• secobarbital

  Monitor Closely (1)secobarbital and perphenazine both increase sedation. Use Caution/Monitor.

• selegiline

  Monitor Closely (1)selegiline, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• selinexor

  Serious - Use Alternative (1)selinexor, perphenazine. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

• selpercatinib

  Monitor Closely (1)selpercatinib increases toxicity of perphenazine by QTc interval. Use Caution/Monitor.

• serdexmethylphenidate/dexmethylphenidate

  Monitor Closely (1)perphenazine, serdexmethylphenidate/dexmethylphenidate. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

• sertraline

  Monitor Closely (1)sertraline and perphenazine both increase QTc interval. Use Caution/Monitor.Minor (1)sertraline will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• sevoflurane

  Monitor Closely (2)sevoflurane and perphenazine both increase sedation. Use Caution/Monitor.
  
  sevoflurane and perphenazine both increase QTc interval. Use Caution/Monitor.

• shepherd's purse

  Monitor Closely (1)perphenazine and shepherd's purse both increase sedation. Use Caution/Monitor.

• siponimod

  Monitor Closely (1)siponimod and perphenazine both increase QTc interval. Use Caution/Monitor.

• smoking

  Monitor Closely (1)smoking decreases levels of perphenazine by increasing metabolism. Use Caution/Monitor. Interaction mainly seen w/chlorpromazine & thioridazine, but may occur w/other phenothiazines.

• sodium oxybate

  Serious - Use Alternative (1)perphenazine, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• sodium sulfate/?magnesium sulfate/potassium chloride

  Monitor Closely (1)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 sulfate/magnesium sulfate

  Monitor Closely (1)sodium sulfate/potassium sulfate/magnesium sulfate increases effects of perphenazine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.

• solifenacin

  Monitor Closely (4)solifenacin decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. 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.
  
  solifenacin and perphenazine both increase QTc interval. Use Caution/Monitor.

• sorafenib

  Monitor Closely (1)sorafenib and perphenazine both increase QTc interval. Use Caution/Monitor.

• sotalol

  Contraindicated (1)perphenazine and sotalol both increase QTc interval. Contraindicated.

• stiripentol

  Monitor Closely (1)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.

• sufentanil

  Monitor Closely (1)sufentanil and perphenazine both increase sedation. Use Caution/Monitor.

• sufentanil SL

  Serious - Use Alternative (1)sufentanil SL, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• sulfamethoxazole

  Monitor Closely (1)perphenazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

• sumatriptan

  Monitor Closely (1)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 intranasal

  Monitor Closely (1)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).

• sunitinib

  Monitor Closely (1)sunitinib and perphenazine both increase QTc interval. Use Caution/Monitor.

• tacrolimus

  Monitor Closely (1)tacrolimus and perphenazine both increase QTc interval. Use Caution/Monitor.

• tamoxifen

  Monitor Closely (1)perphenazine decreases effects of tamoxifen by decreasing metabolism. Use Caution/Monitor. Inhibition of CYP2D6 metabolism to tamoxifen's active metabolite, endoxifen.

• tapentadol

  Monitor Closely (1)tapentadol and perphenazine both increase sedation. Use Caution/Monitor.

• telavancin

  Monitor Closely (1)perphenazine and telavancin both increase QTc interval. Modify Therapy/Monitor Closely.

• temazepam

  Monitor Closely (1)temazepam and perphenazine both increase sedation. Use Caution/Monitor.

• terbinafine

  Monitor Closely (1)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.

• terbutaline

  Monitor Closely (1)perphenazine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• tetrabenazine

  Monitor Closely (1)perphenazine and tetrabenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)tetrabenazine and perphenazine both increase QTc interval. Avoid or Use Alternate Drug.

• thioridazine

  Monitor Closely (2)perphenazine and thioridazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  perphenazine and thioridazine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)perphenazine and thioridazine both increase QTc interval. Avoid or Use Alternate Drug.
  
  perphenazine will increase the level or effect of thioridazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.Minor (1)thioridazine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• thiothixene

  Monitor Closely (2)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.

• timolol

  Monitor Closely (1)perphenazine will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• tiotropium

  Monitor Closely (3)tiotropium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  tiotropium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of tiotropium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• tipranavir

  Minor (1)tipranavir will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• tobacco use

  Monitor Closely (1)tobacco use decreases levels of perphenazine by increasing metabolism. Use Caution/Monitor. Interaction mainly seen w/chlorpromazine & thioridazine, but may occur w/other phenothiazines.

• tolterodine

  Monitor Closely (3)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.Minor (1)perphenazine will increase the level or effect of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• topiramate

  Monitor Closely (1)perphenazine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

• tramadol

  Monitor Closely (1)tramadol and perphenazine both increase sedation. Use Caution/Monitor.

• trandolapril

  Minor (1)perphenazine increases effects of trandolapril by unspecified interaction mechanism. Minor/Significance Unknown.

• tranylcypromine

  Monitor Closely (1)tranylcypromine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• trazodone

  Monitor Closely (1)perphenazine and trazodone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and trazodone both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)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.

• tretinoin

  Serious - Use Alternative (1)perphenazine, tretinoin. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

• tretinoin topical

  Serious - Use Alternative (1)perphenazine, tretinoin topical. Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased phototoxicity.

• triazolam

  Monitor Closely (1)triazolam and perphenazine both increase sedation. Use Caution/Monitor.

• triclofos

  Monitor Closely (1)triclofos and perphenazine both increase sedation. Use Caution/Monitor.

• trifluoperazine

  Monitor Closely (2)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.Serious - Use Alternative (1)perphenazine and trifluoperazine both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)perphenazine will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• trihexyphenidyl

  Monitor Closely (2)trihexyphenidyl decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of trihexyphenidyl by pharmacodynamic synergism. Use Caution/Monitor. Potential for additive anticholinergic effects.

• trimethoprim

  Monitor Closely (1)perphenazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• trimipramine

  Monitor Closely (1)perphenazine and trimipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and trimipramine both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)trimipramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  trimipramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• triprolidine

  Monitor Closely (1)triprolidine and perphenazine both increase sedation. Use Caution/Monitor.

• tropisetron

  Monitor Closely (1)perphenazine and tropisetron both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)perphenazine will increase the level or effect of tropisetron by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• trospium chloride

  Monitor Closely (3)trospium chloride decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  trospium chloride decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.
  
  perphenazine increases effects of trospium chloride by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

• umeclidinium bromide/vilanterol inhaled

  Serious - Use Alternative (1)perphenazine increases toxicity of umeclidinium bromide/vilanterol inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.

• valbenazine

  Monitor Closely (1)valbenazine and perphenazine both increase QTc interval. Use Caution/Monitor.

• vecuronium

  Monitor Closely (3)vecuronium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.
  
  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.

• venlafaxine

  Monitor Closely (2)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).
  
  venlafaxine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and venlafaxine both increase QTc interval. Avoid or Use Alternate Drug.

• vilanterol/fluticasone furoate inhaled

  Serious - Use Alternative (1)perphenazine increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.

• vilazodone

  Monitor Closely (1)vilazodone, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• voriconazole

  Monitor Closely (1)perphenazine and voriconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• vorinostat

  Monitor Closely (1)vorinostat and perphenazine both increase QTc interval. Use Caution/Monitor.

• xylometazoline

  Monitor Closely (2)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.

• yohimbe

  Serious - Use Alternative (1)yohimbe decreases effects of perphenazine by pharmacodynamic antagonism. Contraindicated.

• yohimbine

  Monitor Closely (2)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

  Monitor Closely (1)perphenazine and ziconotide both increase sedation. Use Caution/Monitor.

• ziprasidone

  Monitor Closely (2)perphenazine and ziprasidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  perphenazine and ziprasidone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.

• zolmitriptan

  Monitor Closely (1)zolmitriptan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

• zolpidem

  Monitor Closely (1)perphenazine will increase the level or effect of zolpidem by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Additive effect of decreased alertness and psychomotor performance

• zotepine

  Monitor Closely (2)perphenazine and zotepine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.
  
  perphenazine and zotepine both increase sedation. Use Caution/Monitor.