perphenazine (Rx)

Brand and Other Names:Trilafon
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

tablets

  • 2mg
  • 4mg
  • 8mg
  • 16mg

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

Dosage Forms & Strengths

tablets

  • 2mg
  • 4mg
  • 8mg
  • 16mg

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

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Interactions

Interaction Checker

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            Contraindicated (9)

            • disopyramide

              perphenazine and disopyramide both increase QTc interval. Contraindicated.

            • 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 (88)

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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 (325)

            • 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.

            • 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.

            • 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.

            • 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.

            • 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/lumefantrine

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

            • atomoxetine

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

            • 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.

            • 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.

            • brompheniramine

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

            • buprenorphine

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

            • buprenorphine buccal

              buprenorphine buccal 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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).

            • 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.

            • 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).

            • 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.

            • 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.

            • 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.

            • 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).

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • sevoflurane

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

            • shepherd's purse

              perphenazine and shepherd's purse both increase sedation. 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.

            • 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).

            • 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.

            • 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.

            • 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.

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            Adverse Effects

            >10%

            Akathisia (60%)

            Frequency Not Defined

            Confusion

            Decreased gag reflex

            EPS

            • Akathisia (60%)
            • Dystonia
            • Muscle stiffness
            • Neuroleptic malignant syndrome (infrequent but serious)
            • Parkinsonism
            • Tardive dyskinesia

            Common

            • Anticholinergic effects
            • Sedation
            • Weight gain
            • Oligomenorrhea/amenorrhea
            • Erectile dysfunction

            Less Common

            • Orthostatic hypotension (post-IM inj), tachycardia
            • Anxiety, agitation, cerebral edema, depression, dizziness, euphoria, headache, insomnia, restless, weakness
            • Anorexia, dyspepsia, constipation, ileus
            • Lens opacities (prolonged use)

            Uncommon

            • ECG changes
            • Photosensitivity
            • Pruritis
            • Galactorrhea
            • Ejaculatory disorder
            • Diarrhea
            • Blood dyscrasia

            Rare

            • Seizure
            • Priapism
            • Cholestatic jaundice
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            Warnings

            Black Box Warnings

            Patients with dementia-related psychosis who are treated with antipsychotic drugs are at an increased risk of death as shown in short-term controlled trials. The deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature

            This drug is not approved for the treatment of patients with dementia-related psychosis

            Contraindications

            Documented hypersensitivity to phenothiazines

            Coma, severe hypotension, severe CNS depression, concurrency with large amounts of CNS depressants, poorly controlled seizure disorder, subcortical brain damage with or without hypothalamic damage, myelosuppression, liver damage, blood dyscrasias

            Severe cardiovascular disease

            Lactation

            Cautions

            Avoid using in children with suspected Reye's syndrome

            Use caution in prostatic hypertrophy, stenosing PUD, tardive dyskinesia, hypocalcemia, renal/hepatic impairment, patients who have exhibited a severe reaction to insulin or ECT, history of seizures, asthma, respiratory tract infections, cardiovascular disease

            Perphenazine products can lower convulsive threshold in susceptible individuals; they should be used with caution in alcohol withdrawal and in patients with convulsive disorders; if patient is being treated with an anticonvulsant agent, increased dosage of that agent may be required when perphenazine products are used concomitantly

            Should be used with caution in patients with psychiatric depression; possibility of suicide in depressed patients remains during treatment and until significant remission occurs; this type of patient should not have access to large quantities of this drug

            Caution should be observed in giving it to patients who have previously exhibited severe adverse reactions to other phenothiazines some of the untoward actions of perphenazine tend to appear more frequently when high doses are used; patients should be kept under close supervision

            A significant, not otherwise explained, rise in body temperature may suggest individual intolerance to perphenazine, in which case it should be discontinued

            Patients on large doses who are undergoing surgery should be watched carefully for possible hypotensive phenomena; reduced amounts of anesthetics or central nervous system depressants may be necessary

            If abnormalities in hepatic tests occur, phenothiazine treatment should be discontinued

            Renal function in patients on long-term therapy should be monitored; if blood urea nitrogen (BUN) becomes abnormal, treatment should be discontinued

            Use with caution in patients suffering from respiratory impairment due to acute pulmonary infections, or in chronic respiratory disorders such as severe asthma or emphysema

            Gastritis, nausea and vomiting, dizziness, and tremulousness reported following abrupt cessation of high-dose therapy; reports suggest that these symptoms can be reduced by continuing concomitant antiparkinson agents for several weeks after drug is withdrawn

            Possibility of liver damage, corneal and lenticular deposits, and irreversible dyskinesias should be considered when patients are on long-term therapy

            Because photosensitivity has been reported, undue exposure to sun should be avoided during phenothiazine treatment

            Leukopenia and neutropenia

            • Events of leukopenia/neutropenia and agranulocytosis reported
            • Possible risk factors include preexisting low white blood cell count (WBC) and history of drug induced leukopenia/neutropenia
            • Patients with a preexisting low WBC or a history of drug induced leukopenia/neutropenia should have their complete blood count
            • (CBC) monitored frequently during first few months of therapy discontiue at first sign of a decline in WBC in absence of other causative factors
            • Blood counts should be checked periodically; appearance of signs of blood dyscrasias requires discontinuance of drug and institution of appropriate therapy

            Tardive dyskinesia

            • Risk of developing the syndrome and likelihood that it will become irreversible are believed to increase as the duration of treatment and total cumulative dose of antipsychotic drugs administered to the patient increase; however, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses
            • Antipsychotics should be prescribed in manner that is most likely to minimize occurrence of tardive dyskinesia
            • Chronic antipsychotic treatment should generally be reserved for patients who suffer from chronic illness that 1) is known to respond to antipsychotic drugs, and 2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate
            • In patients who require chronic treatment, the smallest dose and shortest duration of treatment producing a satisfactory clinical response should be sought; the need for continued treatment should be reassessed periodically
            • If signs and symptoms of tardive dyskinesia appear in a patient on antipsychotics, drug discontinuation should be considered; however, some patients may require treatment despite presence of the syndrome

            Neuroleptic malignant syndrome

            • Neuroleptic malignancy syndrome (NMS) may occur; clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmias)
            • Management of NMS should include 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy, 2) intensive symptomatic treatment and medical monitoring, and 3) treatment of any concomitant serious medical problems for which specific treatments are available
            • There is no general agreement about specific pharmacologic treatment regimens for uncomplicated NMS
            • If a patient requires antipsychotic drug treatment after recovery from NMS, reintroduction of drug therapy should be carefully considered; patient should be carefully monitored; recurrences reported
            • If hypotension develops, epinephrine should not be administered since its action is blocked and partially reversed
            • If a vasopressor is needed, norepinephrine or dopamine may be used
            • Severe, acute hypotension has occurred with use of phenothiazines and is particularly likely to occur in patients with mitral insufficiency or pheochromocytoma
            • Rebound hypertension may occur in pheochromocytoma patients

            Drug interaction overview

            • Since phenothiazines and central nervous system depressants (opiates, analgesics, antihistamines, barbiturates) can potentiate each other, less than usual dosage of added drug is recommended and caution is advised when they are administered concomitantly
            • Use with caution in patients who are receiving atropine or related drugs because of additive anticholinergic effects and also in patients who will be exposed to extreme heat or phosphorus insecticides
            • The use of alcohol should be avoided, since additive effects and hypotension may occur; patients should be cautioned that their response to alcohol may be increased while they are being treated with perphenazine products; risk of suicide and danger of overdose may be increased in patients who use alcohol excessively due to its potentiation of drug’s effect
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            Pregnancy & Lactation

            Pregnancy Category: C

            Lactation: avoid

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Antipsychotic that blocks postsynaptic mesolimbic dopaminergic receptors in the brain; it has moderate anticholinergic effects, weak to moderate sedative effects, strong extrapyramidal effects, and strong antiemetic activity

            Pharmacokinetics

            Peak Plasma Time: 1-3 hr; 2-4 hr (metabolite)

            Half-Life: 9-12 hr (; 10-19 hr (metabolite)

            Concentration: 984 pg/mL; 509 pg/mL (metabolite)

            Metabolism: Hepatic P450 enzyme CYP2D6

            Metabolites: 7-hydroxyperphenazine

            Enzymes inhibited: CYP2D6

            Excretion: Urine and feces

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            perphenazine oral
            -
            2 mg tablet
            perphenazine oral
            -
            8 mg tablet
            perphenazine oral
            -
            2 mg tablet
            perphenazine oral
            -
            8 mg tablet
            perphenazine oral
            -
            4 mg tablet
            perphenazine oral
            -
            16 mg tablet
            perphenazine oral
            -
            16 mg tablet
            perphenazine oral
            -
            4 mg tablet
            perphenazine oral
            -
            8 mg tablet
            perphenazine oral
            -
            4 mg tablet
            perphenazine oral
            -
            8 mg tablet
            perphenazine oral
            -
            4 mg tablet
            perphenazine oral
            -
            2 mg tablet
            perphenazine oral
            -
            16 mg tablet
            perphenazine oral
            -
            16 mg tablet
            perphenazine oral
            -
            8 mg tablet
            perphenazine oral
            -
            4 mg tablet
            perphenazine oral
            -
            2 mg tablet

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Patient Education
            perphenazine oral

            PERPHENAZINE - ORAL

            (per-FEN-a-zeen)

            COMMON BRAND NAME(S): Trilafon

            WARNING: There may be a slightly increased risk of serious, possibly fatal side effects (such as heart failure, fast/irregular heartbeat, pneumonia) when this medication is used by older adults with dementia. This medication is not approved for the treatment of dementia-related behavior problems. Discuss the risks and benefits of this medication, as well as other effective and possibly safer treatments for dementia-related behavior problems, with the doctor.

            USES: This medication is used to treat certain mental/mood disorders (e.g., schizophrenia, manic phase of bipolar disorder, schizoaffective disorder). This medicine helps you to think more clearly, feel less nervous, and take part in everyday life. It can reduce aggressive behavior and the desire to hurt yourself/others. It may also help to decrease hallucinations (e.g., hearing/seeing things that are not there). Perphenazine is a psychiatric medication (antipsychotic-type) that works by helping to restore the balance of certain natural substances (e.g., dopamine) in the brain.

            HOW TO USE: Take this medication by mouth, usually 1-3 times a day with or without food or as directed by your doctor.Dosage is based on your medical condition and response to therapy. Your doctor may direct you to take a low dose at first, gradually increasing the dose to lower the chance of side effects such as muscle spasms. Follow your doctor's directions carefully.When you begin treatment, frequent visits to your doctor may be needed to find the best dose for you. Keep all medical/lab appointments.Take this medication regularly to get the most benefit from it. To help you remember, take it at the same time(s) each day.Although you may notice some medication effects soon after starting, it may take as much as 4-6 weeks of regular use to see the full benefit. Do not stop taking this medication without consulting your doctor. Your condition may become worse when the drug is suddenly stopped. Your dose may need to be gradually decreased.Tell your doctor if your condition does not improve or if it worsens.

            SIDE EFFECTS: Drowsiness, constipation, dry mouth, dizziness, lightheadedness, blurred vision, tiredness, or unexplained weight gain may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.Dizziness and lightheadedness can increase the risk of falling. Get up slowly when rising from a sitting or lying position.Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Some people using this medication do not have serious side effects.This drug may cause muscle/nervous system problems (extrapyramidal symptoms-EPS). Your doctor may prescribe another medication to decrease these side effects. Therefore, tell your doctor right away if you notice any of the following side effects: increased anxiety, drooling/trouble swallowing, restlessness/constant need to move, shaking (tremor), shuffling walk, stiff muscles.This medication may cause a condition known as tardive dyskinesia. In some cases, this condition may be permanent. Tell your doctor right away if you develop any involuntary/repetitive muscle movements such as lip smacking/puckering, tongue thrusting, chewing, or finger/toe movements.In rare cases, perphenazine may increase your level of a certain chemical made by the body (prolactin). For females, this increase in prolactin may result in unwanted breast milk, missed/stopped periods, or difficulty becoming pregnant. For males, it may result in decreased sexual ability, inability to produce sperm, or enlarged breasts. If you develop any of these symptoms, tell your doctor right away.Tell your doctor right away if you have any serious side effects, including: difficulty urinating, easy bruising/bleeding, slow heartbeat, signs of infection (e.g., sore throat), severe muscle spasm/cramping (e.g., twisting neck, arching back, eyes rolling up), persistent nausea, seizures, stomach/abdominal pain, yellowing eyes/skin.Get medical help right away if you have any very serious side effects, including: fast/irregular heartbeat, severe dizziness, fainting.This medication may rarely cause a very serious condition called neuroleptic malignant syndrome (NMS). Get medical help right away if you have any of the following symptoms: fever, muscle stiffness/pain/tenderness/weakness, severe tiredness, severe confusion, sweating, fast/irregular heartbeat, dark urine, signs of kidney problems (such as change in the amount of urine).A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before taking perphenazine, tell your doctor or pharmacist if you are allergic to it, or to other phenothiazines (e.g., chlorpromazine, fluphenazine), or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: decreased bone marrow function, serious head injury, liver problems, nervous system problem (such as coma, drug/alcohol overdose, shock), Parkinson's disease, history of alcohol/substance abuse, low blood pressure, breathing problems (such as asthma, emphysema), breast cancer, fast/irregular heartbeat, heart valve problems, a certain adrenal gland tumor (pheochromocytoma), restless legs syndrome, seizure disorder, a certain severe reaction to other medications (neuroleptic malignant syndrome), difficulty urinating (e.g., due to prostate problems).Perphenazine may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can rarely cause serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may cause QT prolongation. Before using perphenazine, tell your doctor or pharmacist of all the drugs you take and if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics "water pills") or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using perphenazine safely.This drug may make you dizzy or drowsy or blur your vision. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness or clear vision until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).This medication may make you more sensitive to the sun. Limit your time in the sun. Avoid tanning booths and sunlamps. Use sunscreen and wear protective clothing when outdoors. Tell your doctor right away if you get sunburned or have skin blisters/redness.Before having surgery, tell your doctor or dentist that you are taking this medication.Caution is advised during hot weather because perphenazine can reduce sweating, increasing your risk for a severe reaction to too much heat (heatstroke). Drink plenty of fluids. Avoid strenuous exercise in hot weather. If you become overheated, promptly seek cooler shelter and/or stop exercising. Seek immediate medical attention if your body temperature is above normal or if you have mental/mood changes, headache, or dizziness.Children may be more sensitive to the side effects of this drug, especially uncontrolled movements.Older adults may be more sensitive to the side effects of this drug, especially dizziness, lightheadedness, drowsiness, extrapyramidal symptoms, tardive dyskinesia, and QT prolongation (see above). Drowsiness, dizziness, and lightheadedness can increase the risk of falling.During pregnancy, this medication should be used only when clearly needed. Babies born to mothers who have used this drug during the last 3 months of pregnancy may rarely develop symptoms including muscle stiffness or shakiness, drowsiness, feeding/breathing difficulties, or constant crying. If you notice any of these symptoms in your newborn especially during their first month, tell the doctor right away.Since untreated mental/mood problems (such as schizophrenia, bipolar disorder, schizoaffective disorder) can be a serious condition, do not stop taking this medication unless directed by your doctor. If you are planning pregnancy, become pregnant, or think you may be pregnant, immediately discuss with your doctor the benefits and risks of using this medication during pregnancy.Perphenazine passes into breast milk and may have undesirable effects on a nursing infant. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug are: certain drugs used for Parkinson's (e.g., bromocriptine, levodopa, pergolide), certain anticholinergic medications (e.g., dicyclomine, scopolamine), drugs affecting liver enzymes that remove perphenazine from your body (e.g., amiodarone, duloxetine, fluoxetine, paroxetine, ritonavir).Tell your doctor or pharmacist if you are taking other products that cause drowsiness such as opioid pain or cough relievers (such as codeine, hydrocodone), alcohol, marijuana (cannabis), drugs for sleep or anxiety (such as alprazolam, lorazepam, zolpidem), muscle relaxants (such as carisoprodol, cyclobenzaprine), or antihistamines (such as cetirizine, diphenhydramine).Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: slow/shallow breathing, inability to wake up (coma).

            NOTES: Do not share this medication with others.Laboratory and/or medical tests (e.g., complete blood count, liver function, eye exams) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

            MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

            STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            Information last revised May 2021. Copyright(c) 2021 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.