amitriptyline/perphenazine (Rx)

Brand and Other Names:
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

amitriptyline/perphenazine

tablet

  • 10mg/2mg
  • 25mg/2mg
  • 10mg/4mg
  • 25mg/4mg
  • 50mg/4mg

Anxiety or Agitation with Depression

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

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

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

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

Do not exceed daily dose of 200 mg/16 mg

Schizophrenia with Depression

Indicated for patients with schizophrenic who have associated depressive symptoms

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

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

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

Do not exceed daily dose of 200 mg/16 mg

Dosing Considerations

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

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

Not recommended

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

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

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Interactions

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            Contraindicated (20)

            • disopyramide

              amitriptyline and disopyramide both increase QTc interval. Contraindicated.

              perphenazine and disopyramide both increase QTc interval. Contraindicated.

            • dronedarone

              dronedarone will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

              dronedarone will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

            • ibutilide

              perphenazine and ibutilide both increase QTc interval. Contraindicated.

            • ibutilide

              amitriptyline and ibutilide both increase QTc interval. Contraindicated.

            • indapamide

              perphenazine and indapamide both increase QTc interval. Contraindicated.

              amitriptyline and indapamide both increase QTc interval. Contraindicated.

            • iobenguane I 123

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

            • metrizamide

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

            • isocarboxazid

              isocarboxazid and amitriptyline both increase serotonin levels. Contraindicated.

            • pentamidine

              perphenazine and pentamidine both increase QTc interval. Contraindicated.

              amitriptyline and pentamidine both increase QTc interval. Contraindicated.

            • phenelzine

              phenelzine and amitriptyline both increase serotonin levels. Contraindicated.

            • pimozide

              perphenazine and pimozide both increase QTc interval. Contraindicated.

            • pimozide

              amitriptyline and pimozide both increase QTc interval. Contraindicated.

            • procainamide

              amitriptyline and procainamide both increase QTc interval. Contraindicated.

              perphenazine and procainamide both increase QTc interval. Contraindicated.

            • procarbazine

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

            • quinidine

              perphenazine and quinidine both increase QTc interval. Contraindicated.

            • quinidine

              quinidine and amitriptyline both increase QTc interval. Contraindicated.

            • safinamide

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

            • selegiline

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

            • sotalol

              perphenazine and sotalol both increase QTc interval. Contraindicated.

              amitriptyline and sotalol both increase QTc interval. Contraindicated.

            • tranylcypromine

              tranylcypromine and amitriptyline both increase serotonin levels. Contraindicated.

            Serious - Use Alternative (181)

            • albuterol

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

            • aminolevulinic acid oral

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

            • aminolevulinic acid topical

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

            • amiodarone

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

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

            • amitriptyline

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

            • amoxapine

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

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

            • amoxapine

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

            • apomorphine

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

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

            • arformoterol

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

            • aripiprazole

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

            • arsenic trioxide

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

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

            • artemether

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

            • artemether/lumefantrine

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

            • artemether/lumefantrine

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

            • benzhydrocodone/acetaminophen

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

            • benzphetamine

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

            • bromocriptine

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

            • buspirone

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

            • cabergoline

              perphenazine decreases effects of cabergoline by pharmacodynamic antagonism. Contraindicated.

            • calcium/magnesium/potassium/sodium oxybates

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

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

            • chlorpromazine

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

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

            • citalopram

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

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

            • clarithromycin

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

            • clarithromycin

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

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

            • clomipramine

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

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

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

            • clonidine

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

            • dacomitinib

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

            • cyclobenzaprine

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

            • dacomitinib

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

            • dasatinib

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

            • degarelix

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

            • desipramine

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

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

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

            • desvenlafaxine

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

            • dofetilide

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

            • dexfenfluramine

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

            • dexmethylphenidate

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

            • dextroamphetamine

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

            • dextromethorphan

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

            • diethylpropion

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

            • dobutamine

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

            • dofetilide

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

            • dolasetron

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

            • dopamine

              perphenazine decreases effects of dopamine by pharmacodynamic antagonism. Contraindicated.

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

            • dopexamine

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

            • dosulepin

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

            • dosulepin

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

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

            • doxepin

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

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

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

            • dronedarone

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

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

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

            • droperidol

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

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

            • duloxetine

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

            • epinephrine

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

            • encorafenib

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

            • ephedrine

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

            • epinephrine

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

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

            • epinephrine racemic

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

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

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

            • erythromycin base

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

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

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

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

            • erythromycin ethylsuccinate

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

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

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

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

            • erythromycin lactobionate

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

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

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

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

            • erythromycin stearate

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

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

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

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

            • escitalopram

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

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

            • fentanyl

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

            • fenfluramine

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

            • fentanyl intranasal

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

            • fentanyl transdermal

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

            • fentanyl transmucosal

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

            • fexinidazole

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

            • fluconazole

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

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

            • fluoxetine

              fluoxetine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug.

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

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

              perphenazine will increase the level or effect of fluoxetine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

              fluoxetine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

            • fluphenazine

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

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

            • fluvoxamine

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

            • formoterol

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

            • formoterol

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

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

            • fosamprenavir

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

            • givosiran

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

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

            • granisetron

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

            • haloperidol

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

            • guanfacine

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

            • haloperidol

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

            • hydrocodone

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

            • hydroxychloroquine sulfate

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

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

            • imipramine

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

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

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

            • iobenguane I 131

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

            • isocarboxazid

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

            • isoproterenol

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

            • itraconazole

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

            • ivosidenib

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

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

            • ketoconazole

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

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

            • lasmiditan

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

            • levodopa

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

            • lefamulin

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

            • levalbuterol

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

            • levodopa inhaled

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

            • levomilnacipran

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

            • linezolid

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

            • lisdexamfetamine

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

            • lisuride

              perphenazine decreases effects of lisuride by pharmacodynamic antagonism. Contraindicated.

            • lofepramine

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

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

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

            • lorcaserin

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

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

            • lumefantrine

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

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

            • macimorelin

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

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

            • maprotiline

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

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

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

            • mefloquine

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

            • methyl aminolevulinate

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

            • meperidine

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

            • metaproterenol

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

            • methamphetamine

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

            • methyldopa

              perphenazine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.

            • methylene blue

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

            • methylenedioxymethamphetamine

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

            • metoclopramide intranasal

              perphenazine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

              perphenazine increases toxicity of metoclopramide intranasal by pharmacodynamic synergism. Avoid or Use Alternate Drug. Potential for additive effects, including increased frequency and severity of tardive dyskinesia, other extrapyramidal symptoms, and neuroleptic malignant syndrome.

              amitriptyline, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

            • midodrine

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

            • mobocertinib

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

            • milnacipran

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

            • mobocertinib

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

            • moxifloxacin

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

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

            • nefazodone

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

            • nilotinib

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

            • netupitant/palonosetron

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

            • nilotinib

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

            • norepinephrine

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

            • nortriptyline

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

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

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

            • octreotide

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

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

            • octreotide (Antidote)

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

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

            • ondansetron

              perphenazine and ondansetron both increase QTc interval. Avoid or Use Alternate Drug. Avoid with congenital long QT syndrome; ECG monitoring recommended with concomitant medications that prolong QT interval, electrolyte abnormalities, CHF, or bradyarrhythmias.

              amitriptyline and ondansetron both increase QTc interval. Avoid or Use Alternate Drug. Avoid with congenital long QT syndrome; ECG monitoring recommended with concomitant medications that prolong QT interval, electrolyte abnormalities, CHF, or bradyarrhythmias.

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

            • ozanimod

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

            • paroxetine

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

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

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

            • palonosetron

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

            • paroxetine

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

            • perphenazine

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

            • phendimetrazine

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

            • phentermine

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

            • phenylephrine

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

            • phenylephrine PO

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

            • pirbuterol

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

            • pitolisant

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

            • pramipexole

              perphenazine decreases effects of pramipexole by pharmacodynamic antagonism. Contraindicated.

            • prochlorperazine

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

            • promazine

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

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

            • promethazine

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

            • propylhexedrine

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

            • protriptyline

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

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

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

            • pseudoephedrine

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

            • quinidine

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

            • quinidine

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

            • ranolazine

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

            • rasagiline

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

            • ribociclib

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

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

            • ropinirole

              perphenazine decreases effects of ropinirole by pharmacodynamic antagonism. Contraindicated.

            • salmeterol

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

            • safinamide

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

            • saquinavir

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

            • selegiline transdermal

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

            • selinexor

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

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

            • sertraline

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

            • 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.

            • sodium oxybate

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

            • St John's Wort

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

            • sufentanil SL

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

            • tedizolid

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

            • terbutaline

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

            • thioridazine

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

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

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

            • toremifene

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

            • trazodone

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

            • trazodone

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

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

            • tretinoin

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

            • tretinoin topical

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

            • trifluoperazine

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

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

            • trimipramine

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

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

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

            • umeclidinium bromide/vilanterol inhaled

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

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

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

            • vandetanib

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

            • venlafaxine

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

            • vemurafenib

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

            • venlafaxine

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

            • vilanterol/fluticasone furoate inhaled

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

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

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

            • vilazodone

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

            • yohimbe

              yohimbe decreases effects of perphenazine by pharmacodynamic antagonism. Contraindicated.

            • vortioxetine

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

            • xylometazoline

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

            • yohimbe

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

            • yohimbine

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

            • ziprasidone

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

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

            Monitor Closely (486)

            • 5-HTP

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

            • abiraterone

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

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

            • abobotulinumtoxinA

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

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

            • aclidinium

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

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

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

            • albiglutide

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

            • albuterol

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

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

            • albuterol

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

            • alfentanil

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

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

            • alfuzosin

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

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

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

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

            • almotriptan

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

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

            • alprazolam

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

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

            • amifampridine

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

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

            • amiodarone

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

            • amitriptyline

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

            • amobarbital

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

              amobarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

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

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

            • amoxapine

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

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

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

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

            • anticholinergic/sedative combos

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

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

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

              anticholinergic/sedative combos decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

            • apomorphine

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

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

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

            • aprepitant

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

            • arformoterol

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

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

            • arformoterol

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

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

            • aripiprazole

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

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

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

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

            • armodafinil

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

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

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

            • artemether

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

            • atazanavir

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

              atazanavir increases levels of amitriptyline by unspecified interaction mechanism. Use Caution/Monitor.

            • 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.

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

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

            • atorvastatin

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

            • atracurium

              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.

            • atracurium

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

            • atropine

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

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

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

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

            • atropine IV/IM

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

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

              atropine IV/IM decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

              atropine IV/IM and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • azelastine

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

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

            • azithromycin

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

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

            • baclofen

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

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

            • bedaquiline

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

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

            • belladonna alkaloids

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

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

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

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

            • belladonna and opium

              belladonna and opium and perphenazine both increase sedation. Use Caution/Monitor.

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

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

              belladonna and opium and amitriptyline both increase sedation. Use Caution/Monitor.

              belladonna and opium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

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

            • benperidol

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

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

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

            • benzhydrocodone/acetaminophen

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

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

            • benzphetamine

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

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

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

            • benztropine

              benztropine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely. Additive anticholinergic adverse effects may be seen with concurrent use.

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

            • bethanechol

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

            • brexanolone

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

            • brompheniramine

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

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

            • buprenorphine

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

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

            • buprenorphine buccal

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

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

            • buprenorphine subdermal implant

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

            • buprenorphine, long-acting injection

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

            • buprenorphine, long-acting injection

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

            • bupropion

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

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

              perphenazine increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

              amitriptyline increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

            • butabarbital

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

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

              butabarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

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

            • butalbital

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

              butalbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

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

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

            • butorphanol

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

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

            • caffeine

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

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

            • carbachol

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

            • carbinoxamine

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

            • carbamazepine

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

            • carbinoxamine

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

            • carisoprodol

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

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

            • carvedilol

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

            • cenobamate

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

            • cenobamate

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

            • ceritinib

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

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

            • cevimeline

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

            • chloral hydrate

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

            • chloral hydrate

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

            • chlordiazepoxide

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

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

            • chloroquine

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

            • chlorpheniramine

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

            • chlorpheniramine

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

            • chlorpromazine

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

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

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

            • chlorzoxazone

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

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

            • cigarette smoking

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

            • cimetidine

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

            • cinnarizine

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

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

            • cisatracurium

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

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

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

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

            • citalopram

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

            • clarithromycin

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

            • clemastine

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

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

            • clobazam

              amitriptyline, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

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

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

            • clomipramine

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

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

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

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

            • clonazepam

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

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

            • clonidine

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

            • clorazepate

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

            • clorazepate

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

            • clotrimazole

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

            • clozapine

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

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

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

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

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

            • cobicistat

              cobicistat will increase the level or effect of perphenazine by Other (see comment). Modify Therapy/Monitor Closely. A decrease in the dose of antipsychotics that are metabolized by CYP3A or CYP2D6 may be needed upon coadministration.

              cobicistat will increase the level or effect of amitriptyline by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.

              cobicistat will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Carefully titrate antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant response

            • cocaine

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

            • codeine

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

            • codeine

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

            • conivaptan

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

            • crizotinib

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

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

            • cyclizine

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

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

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

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

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

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

            • cyclobenzaprine

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

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

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

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

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

            • cyclosporine

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

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

            • cyproheptadine

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

            • cyproheptadine

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

            • dantrolene

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

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

            • darifenacin

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

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

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

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

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

            • darunavir

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

            • dasatinib

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

            • dasatinib

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

            • debrisoquine

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

            • degarelix

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

            • desflurane

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

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

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

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

            • desipramine

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

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

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

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

            • desvenlafaxine

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

            • deutetrabenazine

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

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

            • deutetrabenazine

              perphenazine and deutetrabenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely. The risk for parkinsonism, neuroleptic malignant syndrome, and akathisia may be increased by concomitant use of deutetrabenazine and dopamine antagonists or antipsychotics.

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

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

            • dexchlorpheniramine

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

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

            • dexfenfluramine

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

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

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

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

            • dexmedetomidine

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

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

            • dexmethylphenidate

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

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

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

            • dextroamphetamine

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

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

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

              amitriptyline increases effects of dextroamphetamine by unknown mechanism. Use Caution/Monitor.

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

            • dextromethorphan

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

            • dextromoramide

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

            • dextromoramide

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

            • diamorphine

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

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

            • diazepam

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

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

            • diazepam intranasal

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

            • dicyclomine

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

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

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

            • dicyclomine

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

            • diethylpropion

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

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

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

            • difenoxin hcl

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

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

            • dihydroergotamine

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

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

            • dihydroergotamine intranasal

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

            • dimenhydrinate

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

            • diltiazem

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

            • dimenhydrinate

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

            • diphenhydramine

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

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

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

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

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

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

            • diphenoxylate hcl

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

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

            • dipipanone

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

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

            • dobutamine

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

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

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

            • dofetilide

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

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

            • dolasetron

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

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

            • donepezil

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

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

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

            • dopamine

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

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

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

            • dopexamine

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

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

            • dosulepin

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

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

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

            • doxepin

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

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

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

            • doxylamine

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

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

            • droperidol

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

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

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

            • duloxetine

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

            • echothiophate iodide

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

            • efavirenz

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

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

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

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

            • elagolix

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

            • eletriptan

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

            • eletriptan

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

            • eliglustat

              eliglustat increases levels of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the concomitant drug and titrate to clinical effect.

              eliglustat increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.

              eliglustat increases levels of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the concomitant drug and titrate to clinical effect.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; A decrease in dose of the neuroleptic may be needed when coadministered.

              elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

            • encorafenib

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

            • entrectinib

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

            • entrectinib

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

            • ephedrine

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

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

              amitriptyline increases effects of ephedrine by unknown mechanism. Use Caution/Monitor.

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

            • epinephrine

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

              amitriptyline increases effects of epinephrine by unknown mechanism. Use Caution/Monitor.

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

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

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

            • epinephrine inhaled

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

            • epinephrine racemic

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

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

            • epinephrine racemic

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

              amitriptyline increases effects of epinephrine racemic by unknown mechanism. Use Caution/Monitor.

            • ergoloid mesylates

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

            • ergotamine

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

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

            • escitalopram

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

            • esketamine intranasal

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

            • eslicarbazepine acetate

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

            • esomeprazole

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

            • estazolam

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

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

            • ethanol

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

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

            • etomidate

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

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

            • etravirine

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

            • fedratinib

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

            • ezogabine

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

            • fedratinib

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

            • felbamate

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

            • felodipine

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

            • fenfluramine

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

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

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

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

              fenfluramine, amitriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration with drugs that increase serotoninergic effects may increase the risk of serotonin syndrome.

            • fentanyl

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

            • fesoterodine

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

            • fesoterodine

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

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

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

            • fingolimod

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

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

            • flavoxate

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

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

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

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

            • flecainide

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

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

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

            • flibanserin

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

            • fluconazole

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

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

            • fluoxetine

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

            • fluphenazine

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

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

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

            • flurazepam

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

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

            • fluvoxamine

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

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

            • formoterol

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

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

            • fosamprenavir

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

            • foscarnet

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

            • foscarnet

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

            • fosphenytoin

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

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

            • fostemsavir

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

            • frovatriptan

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

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

            • gabapentin

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

            • 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.

            • gabapentin enacarbil

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

            • galantamine

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

            • glecaprevir/pibrentasvir

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

            • glycopyrrolate

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

              amitriptyline increases levels of glycopyrrolate by unknown mechanism. Use Caution/Monitor.

            • glycopyrrolate inhaled

              perphenazine increases toxicity of glycopyrrolate inhaled by unknown mechanism. Use Caution/Monitor.

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

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

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

              amitriptyline increases levels of glycopyrrolate inhaled by unknown mechanism. Use Caution/Monitor.

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

            • glycopyrronium tosylate topical

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

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

            • grapefruit

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

            • guanfacine

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

            • haloperidol

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

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

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

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

            • henbane

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

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

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

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

            • homatropine

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

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

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

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

            • huperzine A

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

            • hydrocodone

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

            • hydrocodone

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

            • hydromorphone

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

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

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

            • hydroxyzine

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

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

            • hyoscyamine

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

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

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

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

            • hyoscyamine spray

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

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

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

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

            • iloperidone

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

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

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

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

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

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

            • imipramine

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

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

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

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

            • incobotulinumtoxinA

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

            • indacaterol, inhaled

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

            • indacaterol, inhaled

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

            • indinavir

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

            • insulin degludec

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

            • insulin degludec/insulin aspart

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

            • insulin inhaled

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

            • ipratropium

              ipratropium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. Due to the poor systemic absorption of ipratropium, interaction unlikely at regularly recommended dosages.

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

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

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

            • isoniazid

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

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

            • isoproterenol

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

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

            • isoproterenol

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

            • istradefylline

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

            • itraconazole

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

            • ivacaftor

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

            • ketamine

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

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

            • ketoconazole

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

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

            • ketotifen, ophthalmic

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

            • ketotifen, ophthalmic

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

            • L-tryptophan

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

            • lapatinib

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

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

            • lasmiditan

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

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

              amitriptyline increases effects of lasmiditan by serotonin levels. Use Caution/Monitor. Coadministration may increase risk of serotonin syndrome.

            • lemborexant

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

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

            • letermovir

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

            • levalbuterol

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

            • levalbuterol

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

            • levofloxacin

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

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

            • levomilnacipran

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

            • levorphanol

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

            • levorphanol

              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

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

              amitriptyline, lisdexamfetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue along with concomitant serotonergic drug(s).

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

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

            • lithium

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

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

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

            • lofepramine

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

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

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

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

            • lofexidine

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

              amitriptyline decreases effects of lofexidine by unspecified interaction mechanism. Use Caution/Monitor.

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

            • loprazolam

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

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

            • loratadine

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

            • lorazepam

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

            • lorazepam

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

            • lorcaserin

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

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

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

            • lormetazepam

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

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

            • loxapine

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

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

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

            • loxapine inhaled

              loxapine inhaled and perphenazine both increase sedation. Use Caution/Monitor.

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

              loxapine inhaled and amitriptyline both increase sedation. Use Caution/Monitor.

            • lsd

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

            • lumefantrine

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

            • lurasidone

              lurasidone, amitriptyline. Either increases toxicity of the other by sedation. Use Caution/Monitor. Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

              lurasidone, perphenazine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

              lurasidone increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of hypotension with concurrent use. Monitor blood pressure and adjust dose of antihypertensive agent as needed.

            • maprotiline

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

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

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

            • maraviroc

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

            • marijuana

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

            • marijuana

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

            • meclizine

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

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

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

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

            • melatonin

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

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

            • meperidine

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

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

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

            • meprobamate

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

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

            • metaproterenol

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

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

            • metaxalone

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

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

            • metformin

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

            • methadone

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

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

            • methadone

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

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

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

            • methamphetamine

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

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

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

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

            • methocarbamol

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

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

            • methoxsalen

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

            • methscopolamine

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

            • methscopolamine

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

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

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

            • methylenedioxymethamphetamine

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

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

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

            • methylergonovine

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

            • methylphenidate

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

            • methylphenidate

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

              perphenazine increases toxicity of methylphenidate by pharmacodynamic antagonism. Use Caution/Monitor. Closely monitor for signs of altered clinical response to either methylphenidate or an antipsychotic when using these drugs in combination.

            • metoclopramide

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

            • metoprolol

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

            • mexiletine

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

            • midazolam

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

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

            • midazolam intranasal

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

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

            • midodrine

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

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

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

            • mifepristone

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

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

            • milnacipran

              milnacipran, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • mipomersen

              mipomersen, amitriptyline. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

            • mirabegron

              mirabegron will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              mirabegron will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • mirtazapine

              perphenazine and mirtazapine both increase sedation. Use Caution/Monitor.

              amitriptyline and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely.

              amitriptyline and mirtazapine both increase sedation. Use Caution/Monitor.

            • modafinil

              perphenazine increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              amitriptyline increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              modafinil will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

            • morphine

              perphenazine will increase the level or effect of morphine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              amitriptyline and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

              morphine and perphenazine both increase sedation. Use Caution/Monitor.

              morphine and amitriptyline both increase sedation. Use Caution/Monitor.

            • motherwort

              perphenazine and motherwort both increase sedation. Use Caution/Monitor.

              amitriptyline and motherwort both increase sedation. Use Caution/Monitor.

            • moxonidine

              perphenazine and moxonidine both increase sedation. Use Caution/Monitor.

              amitriptyline and moxonidine both increase sedation. Use Caution/Monitor.

            • nabilone

              perphenazine and nabilone both increase sedation. Use Caution/Monitor.

              amitriptyline and nabilone both increase sedation. Use Caution/Monitor.

            • nalbuphine

              nalbuphine and amitriptyline both increase sedation. Use Caution/Monitor.

              nalbuphine and perphenazine both increase sedation. Use Caution/Monitor.

            • naratriptan

              naratriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

              naratriptan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • nebivolol

              perphenazine will increase the level or effect of nebivolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • nefazodone

              nefazodone will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              nefazodone will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nefopam

              nefopam, amitriptyline. Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Use combination with caution.

            • nelfinavir

              nelfinavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • neostigmine

              neostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • nicardipine

              nicardipine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nifedipine

              nifedipine will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • norepinephrine

              perphenazine, norepinephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

              amitriptyline increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              perphenazine increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              amitriptyline increases effects of norepinephrine by unknown mechanism. Use Caution/Monitor.

            • nortriptyline

              amitriptyline and nortriptyline both increase sedation. Use Caution/Monitor.

              perphenazine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              amitriptyline and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              perphenazine and nortriptyline both increase sedation. Use Caution/Monitor.

            • ofloxacin

              amitriptyline and ofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

              perphenazine and ofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

            • olanzapine

              olanzapine and perphenazine both increase sedation. Use Caution/Monitor.

              olanzapine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              olanzapine and amitriptyline both increase sedation. Use Caution/Monitor.

            • oliceridine

              amitriptyline, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely.

              oliceridine, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation. Increased risk of hypotension if ability to maintain blood pressure has been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (eg, phenothiazines or general anesthetics).

              amitriptyline increases toxicity of oliceridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor for signs of urinary retention or reduced gastric motility if oliceridine is coadministered with anticholinergics.

            • olodaterol inhaled

              amitriptyline and olodaterol inhaled both increase QTc interval. Use Caution/Monitor. TCAs prolong the QTc interval and may potentiate the effects of beta2 agonists on the cardiovascular system; increased risk of ventricular arrhythmias

              perphenazine and olodaterol inhaled both increase QTc interval. Use Caution/Monitor. Drugs that prolong the QTc interval and may potentiate the effects of beta2 agonists on the cardiovascular system; increased risk of ventricular arrhythmias

            • onabotulinumtoxinA

              onabotulinumtoxinA and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

              onabotulinumtoxinA decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              onabotulinumtoxinA decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

              perphenazine increases effects of onabotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • opium tincture

              opium tincture and perphenazine both increase sedation. Use Caution/Monitor.

              opium tincture and amitriptyline both increase sedation. Use Caution/Monitor.

            • orphenadrine

              amitriptyline and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

              orphenadrine and perphenazine both increase sedation. Use Caution/Monitor.

              orphenadrine and amitriptyline both increase sedation. Use Caution/Monitor.

            • osilodrostat

              osilodrostat and amitriptyline both increase QTc interval. Use Caution/Monitor.

            • osimertinib

              osimertinib and perphenazine both increase QTc interval. Use Caution/Monitor. Conduct periodic monitoring with ECGs and electrolytes in patients taking drugs known to prolong the QTc interval.

            • osimertinib

              osimertinib and amitriptyline both increase QTc interval. Use Caution/Monitor. Conduct periodic monitoring with ECGs and electrolytes in patients taking drugs known to prolong the QTc interval.

            • oxaliplatin

              oxaliplatin will increase the level or effect of amitriptyline by Other (see comment). Use Caution/Monitor. Monitor for ECG changes if therapy is initiated in patients with drugs known to prolong QT interval.

            • oxazepam

              oxazepam and perphenazine both increase sedation. Use Caution/Monitor.

              oxazepam and amitriptyline both increase sedation. Use Caution/Monitor.

            • oxybutynin

              oxybutynin decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

              oxybutynin decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              perphenazine increases effects of oxybutynin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              oxybutynin and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • oxybutynin topical

              oxybutynin topical decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              perphenazine increases effects of oxybutynin topical by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              oxybutynin topical and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              oxybutynin topical decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

            • oxybutynin transdermal

              oxybutynin transdermal decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

              oxybutynin transdermal decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              perphenazine increases effects of oxybutynin transdermal by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              oxybutynin transdermal and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • oxycodone

              oxycodone and perphenazine both increase sedation. Use Caution/Monitor.

              perphenazine will increase the level or effect of oxycodone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              oxycodone and amitriptyline both increase sedation. Use Caution/Monitor.

            • oxymetazoline intranasal

              amitriptyline increases effects of oxymetazoline intranasal by pharmacodynamic synergism. Use Caution/Monitor. TCAs inhibit norepinephrine uptake in adrenergic neurons, thereby increasing synaptic norepinephrine levels. Coadministration with alpha1 agonists may cause increased adrenergic receptor stimulation. When oxymetazoline is combined with intranasal tetracaine for dental anesthesia, avoid or use alternant anesthetic in patients taking TCAs.

            • oxymorphone

              perphenazine will increase the level or effect of oxymorphone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              oxymorphone and perphenazine both increase sedation. Use Caution/Monitor.

            • oxymorphone

              oxymorphone and amitriptyline both increase sedation. Use Caution/Monitor.

            • ozanimod

              ozanimod and perphenazine both increase QTc interval. Modify Therapy/Monitor Closely. The potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties.

              ozanimod and amitriptyline both increase QTc interval. Modify Therapy/Monitor Closely. The potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties.

            • paliperidone

              amitriptyline and paliperidone both increase QTc interval. Modify Therapy/Monitor Closely.

              paliperidone and perphenazine both increase sedation. Use Caution/Monitor.

              paliperidone and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              paliperidone and amitriptyline both increase sedation. Use Caution/Monitor.

              perphenazine and paliperidone both increase QTc interval. Modify Therapy/Monitor Closely.

            • pancuronium

              pancuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              perphenazine increases effects of pancuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              pancuronium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

              pancuronium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

            • panobinostat

              panobinostat will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Panobinostat can increase the levels and effects of sensitive CYP2D6 substrates or those with a narrow therapeutic index CYP2D6.

            • papaveretum

              papaveretum and amitriptyline both increase sedation. Use Caution/Monitor.

            • papaveretum

              papaveretum and perphenazine both increase sedation. Use Caution/Monitor.

            • papaverine

              perphenazine and papaverine both increase sedation. Use Caution/Monitor.

              amitriptyline and papaverine both increase sedation. Use Caution/Monitor.

            • paroxetine

              paroxetine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

              amitriptyline and paroxetine both increase QTc interval. Modify Therapy/Monitor Closely.

            • pasireotide

              amitriptyline and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.

              perphenazine and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.

            • pazopanib

              perphenazine and pazopanib both increase QTc interval. Use Caution/Monitor.

              amitriptyline and pazopanib both increase QTc interval. Use Caution/Monitor.

            • peginterferon alfa 2b

              peginterferon alfa 2b, perphenazine. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.

              peginterferon alfa 2b, amitriptyline. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.

            • pentazocine

              amitriptyline and pentazocine both increase serotonin levels. Modify Therapy/Monitor Closely.

              pentazocine and perphenazine both increase sedation. Use Caution/Monitor.

              pentazocine and amitriptyline both increase sedation. Use Caution/Monitor.

            • pentobarbital

              pentobarbital and perphenazine both increase sedation. Use Caution/Monitor.

              pentobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              pentobarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

              pentobarbital and amitriptyline both increase sedation. Use Caution/Monitor.

            • perphenazine

              perphenazine and amitriptyline both increase sedation. Use Caution/Monitor.

            • phendimetrazine

              perphenazine increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              perphenazine, phendimetrazine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • phendimetrazine

              amitriptyline increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenelzine

              phenelzine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • phenobarbital

              phenobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              phenobarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

              phenobarbital and perphenazine both increase sedation. Use Caution/Monitor.

              phenobarbital and amitriptyline both increase sedation. Use Caution/Monitor.

            • phentermine

              perphenazine increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              amitriptyline increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              perphenazine, phentermine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • phenylephrine

              perphenazine increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              amitriptyline increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              perphenazine, phenylephrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • phenylephrine PO

              perphenazine increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

              perphenazine, phenylephrine PO. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • phenylephrine PO

              amitriptyline increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

            • phenylephrine ophthalmic

              amitriptyline, phenylephrine ophthalmic. Other (see comment). Use Caution/Monitor. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • phenytoin

              phenytoin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor therapeutic efficacy of amitriptyline; an increased dose may be required. Serum phenytoin levels should be obtained when tricyclic antidepressant agents are added to therapy due to the potential for impaired phenytoin metabolism and decreased seizure threshold. Tricyclic antidepressants when given concomitantly with anticonvulsants can increase CNS depression.

              phenytoin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor therapeutic efficacy of amitriptyline; an increased dose may be required. Serum phenytoin levels should be obtained when tricyclic antidepressant agents are added to therapy due to the potential for impaired phenytoin metabolism and decreased seizure threshold. Tricyclic antidepressants when given concomitantly with anticonvulsants can increase CNS depression.

            • pholcodine

              perphenazine and pholcodine both increase sedation. Use Caution/Monitor.

              amitriptyline and pholcodine both increase sedation. Use Caution/Monitor.

            • physostigmine

              physostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • pimozide

              perphenazine and pimozide both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              perphenazine and pimozide both increase sedation. Use Caution/Monitor.

            • pilocarpine

              pilocarpine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • pimozide

              pimozide and amitriptyline both increase sedation. Use Caution/Monitor.

            • pirbuterol

              amitriptyline increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              perphenazine increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ponatinib

              ponatinib increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • porfimer

              perphenazine, porfimer. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced photosensitivity.

            • posaconazole

              perphenazine and posaconazole both increase QTc interval. Modify Therapy/Monitor Closely.

              amitriptyline and posaconazole both increase QTc interval. Modify Therapy/Monitor Closely.

            • pralidoxime

              perphenazine increases effects of pralidoxime by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              pralidoxime decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

              pralidoxime decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              pralidoxime and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • pregabalin

              pregabalin, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

            • primidone

              primidone and perphenazine both increase sedation. Use Caution/Monitor.

            • primidone

              primidone will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              primidone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

              primidone and amitriptyline 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.

              prochlorperazine and amitriptyline both increase QTc interval. Use Caution/Monitor.

              perphenazine and prochlorperazine both increase sedation. Use Caution/Monitor.

              prochlorperazine and amitriptyline both increase sedation. Use Caution/Monitor.

            • promethazine

              promethazine and amitriptyline both increase sedation. Use Caution/Monitor.

              promethazine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

              perphenazine and promethazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              promethazine and perphenazine both increase sedation. Use Caution/Monitor.

              promethazine and amitriptyline both increase QTc interval. Use Caution/Monitor.

            • propafenone

              perphenazine will increase the level or effect of propafenone by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

              propafenone will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • propantheline

              propantheline and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • propantheline

              propantheline decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              propantheline decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

              perphenazine increases effects of propantheline by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • propofol

              propofol and amitriptyline both increase sedation. Use Caution/Monitor.

              propofol and perphenazine both increase sedation. Use Caution/Monitor.

            • propranolol

              perphenazine will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • propylhexedrine

              amitriptyline increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • propylhexedrine

              perphenazine increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              perphenazine, propylhexedrine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

            • protriptyline

              amitriptyline and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              perphenazine and protriptyline both increase sedation. Use Caution/Monitor.

              amitriptyline and protriptyline both increase sedation. Use Caution/Monitor.

            • pseudoephedrine

              perphenazine, pseudoephedrine. Mechanism: unknown. Use Caution/Monitor. Consider avoiding use of pseudoephedrine in patients receiving phenothiazines (especially thioridazine) due to the potential risk of cardiac arrhythmia or sudden death. Monitor for evidence of ventricular arrhythmias during concomitant use.

            • pyridostigmine

              pyridostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • quazepam

              quazepam and perphenazine both increase sedation. Use Caution/Monitor.

              quazepam and amitriptyline both increase sedation. Use Caution/Monitor.

            • quercetin

              quercetin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • quetiapine

              perphenazine and quetiapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              perphenazine and quetiapine both increase sedation. Use Caution/Monitor.

            • quetiapine

              quetiapine and amitriptyline both increase sedation. Use Caution/Monitor.

              quetiapine, amitriptyline. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Avoid use with drugs that prolong QT and in patients with risk factors for prolonged QT interval. Postmarketing cases show QT prolongation with overdose in patients with concomitant illness or with drugs known to cause electrolyte imbalance or prolong QT.

            • quinidine

              quinidine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • quinine

              perphenazine and quinine both increase QTc interval. Use Caution/Monitor.

              amitriptyline and quinine both increase QTc interval. Use Caution/Monitor.

            • ramelteon

              perphenazine and ramelteon both increase sedation. Use Caution/Monitor.

              amitriptyline and ramelteon both increase sedation. Use Caution/Monitor.

            • ranolazine

              amitriptyline and ranolazine both increase QTc interval. Modify Therapy/Monitor Closely.

              perphenazine and ranolazine both increase QTc interval. Modify Therapy/Monitor Closely.

            • rapacuronium

              perphenazine increases effects of rapacuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              rapacuronium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

              rapacuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              rapacuronium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

            • remifentanil

              amitriptyline, remifentanil. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. May also increase risk of serotonin syndrome.

            • remimazolam

              remimazolam, perphenazine. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

            • remimazolam

              remimazolam, amitriptyline. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

            • rifabutin

              rifabutin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              rifabutin decreases levels of amitriptyline by increasing metabolism. Use Caution/Monitor.

            • rifampin

              rifampin will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              rifampin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              rifampin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • rifapentine

              rifapentine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rilpivirine

              rilpivirine increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

            • rimabotulinumtoxinB

              perphenazine, rimabotulinumtoxinB. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Anticholinergics may enhance botulinum toxin effects. Closely monitor for increased neuromuscular blockade.

            • risperidone

              amitriptyline and risperidone both increase QTc interval. Modify Therapy/Monitor Closely.

              risperidone and amitriptyline both increase sedation. Use Caution/Monitor.

              perphenazine and risperidone both increase sedation. Use Caution/Monitor.

              perphenazine and risperidone both increase QTc interval. Modify Therapy/Monitor Closely.

              perphenazine and risperidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

            • ritonavir

              ritonavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              ritonavir will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • rizatriptan

              rizatriptan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • rivastigmine

              rivastigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • rizatriptan

              rizatriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

            • rocuronium

              rocuronium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

              rocuronium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              perphenazine increases effects of rocuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              rocuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • rolapitant

              rolapitant will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.

              rolapitant will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.

            • romidepsin

              perphenazine and romidepsin both increase QTc interval. Modify Therapy/Monitor Closely.

              amitriptyline and romidepsin both increase QTc interval. Modify Therapy/Monitor Closely.

            • salmeterol

              perphenazine increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              amitriptyline increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • SAMe

              amitriptyline and SAMe both increase serotonin levels. Modify Therapy/Monitor Closely.

            • scopolamine

              scopolamine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              scopolamine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

              perphenazine increases effects of scopolamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • sarecycline

              sarecycline will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

            • scopolamine

              scopolamine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • scullcap

              perphenazine and scullcap both increase sedation. Use Caution/Monitor.

              amitriptyline and scullcap both increase sedation. Use Caution/Monitor.

            • secobarbital

              secobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              secobarbital and amitriptyline both increase sedation. Use Caution/Monitor.

              secobarbital and perphenazine both increase sedation. Use Caution/Monitor.

            • selegiline

              selegiline, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • selpercatinib

              selpercatinib increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor.

            • selpercatinib

              selpercatinib increases toxicity of perphenazine by QTc interval. Use Caution/Monitor.

            • sevoflurane

              sevoflurane and amitriptyline both increase sedation. Use Caution/Monitor.

              sevoflurane and perphenazine both increase sedation. Use Caution/Monitor.

            • shepherd's purse

              perphenazine and shepherd's purse both increase sedation. Use Caution/Monitor.

              amitriptyline and shepherd's purse both increase sedation. Use Caution/Monitor.

            • simvastatin

              simvastatin will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • smoking

              smoking decreases levels of perphenazine by increasing metabolism. Use Caution/Monitor. Interaction mainly seen w/chlorpromazine & thioridazine, but may occur w/other phenothiazines.

            • sirolimus

              sirolimus will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • sodium sulfate/?magnesium sulfate/potassium chloride

              sodium sulfate/?magnesium sulfate/potassium chloride increases effects of amitriptyline by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of seizures when using higher dose of magnesium sulfate together with drugs that lower the seizure threshold.

              sodium sulfate/?magnesium sulfate/potassium chloride increases effects of perphenazine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.

            • sodium sulfate/potassium sulfate/magnesium sulfate

              sodium sulfate/potassium sulfate/magnesium sulfate increases effects of amitriptyline by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of seizures when using higher dose of magnesium sulfate together with drugs that lower the seizure threshold.

              sodium sulfate/potassium sulfate/magnesium sulfate increases effects of perphenazine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.

            • sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol

              amitriptyline, sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol. Other (see comment). Use Caution/Monitor. Comment: Caution when bowel preps are used with drugs that cause SIADH or NSAIDs; increased risk for water retention or electrolyte imbalance.

            • solifenacin

              solifenacin decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              solifenacin decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

              perphenazine increases effects of solifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • solifenacin

              solifenacin and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • sorafenib

              sorafenib and amitriptyline both increase QTc interval. Use Caution/Monitor.

              sorafenib and perphenazine both increase QTc interval. Use Caution/Monitor.

            • St John's Wort

              St John's Wort will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

              St John's Wort will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • stiripentol

              stiripentol, perphenazine. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

            • stiripentol

              stiripentol, amitriptyline. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

            • succinylcholine

              succinylcholine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

            • sufentanil

              sufentanil and amitriptyline both increase sedation. Use Caution/Monitor.

              sufentanil and perphenazine both increase sedation. Use Caution/Monitor.

            • sufentanil SL

              sufentanil SL, amitriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

            • sulfamethoxazole

              perphenazine and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

            • sulfamethoxazole

              amitriptyline and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

            • sumatriptan

              sumatriptan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

              sumatriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

            • sumatriptan intranasal

              sumatriptan intranasal, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

              sumatriptan intranasal and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

            • suvorexant

              suvorexant and amitriptyline both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary

            • tamoxifen

              perphenazine decreases effects of tamoxifen by decreasing metabolism. Use Caution/Monitor. Inhibition of CYP2D6 metabolism to tamoxifen's active metabolite, endoxifen.

            • tacrolimus

              tacrolimus will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • tapentadol

              tapentadol and perphenazine both increase sedation. Use Caution/Monitor.

              amitriptyline and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.

              tapentadol and amitriptyline both increase sedation. Use Caution/Monitor.

            • telavancin

              perphenazine and telavancin both increase QTc interval. Modify Therapy/Monitor Closely.

              amitriptyline and telavancin both increase QTc interval. Modify Therapy/Monitor Closely.

            • temazepam

              temazepam and amitriptyline both increase sedation. Use Caution/Monitor.

              temazepam and perphenazine both increase sedation. Use Caution/Monitor.

            • terbinafine

              terbinafine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.

              terbinafine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.

            • terbutaline

              perphenazine increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              amitriptyline increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • teriflunomide

              teriflunomide decreases levels of amitriptyline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

            • tetrabenazine

              perphenazine and tetrabenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Modify Therapy/Monitor Closely.

            • thioridazine

              perphenazine and thioridazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              thioridazine and amitriptyline both increase sedation. Use Caution/Monitor.

              perphenazine and thioridazine both increase sedation. Use Caution/Monitor.

            • thiothixene

              perphenazine and thiothixene both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              perphenazine and thiothixene both increase sedation. Use Caution/Monitor.

              thiothixene and amitriptyline both increase sedation. Use Caution/Monitor.

            • timolol

              perphenazine will increase the level or effect of timolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • tiotropium

              tiotropium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • tiotropium

              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 pharmacodynamic antagonism. Use Caution/Monitor.

              perphenazine increases effects of tolterodine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              tolterodine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              tolterodine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • tolvaptan

              tolvaptan will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • topiramate

              perphenazine and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • topiramate

              amitriptyline and topiramate both increase sedation. Modify Therapy/Monitor Closely.

              topiramate increases toxicity of amitriptyline by unspecified interaction mechanism. Use Caution/Monitor. Amitriptyline levels may increase; adjust dose based on clinical response and not on basis of plasma levels.

            • tramadol

              tramadol and perphenazine both increase sedation. Use Caution/Monitor.

              amitriptyline and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

              tramadol and amitriptyline both increase sedation. Use Caution/Monitor.

            • tranylcypromine

              tranylcypromine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • trazodone

              trazodone will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              amitriptyline and trazodone both decrease cholinergic effects/transmission. Use Caution/Monitor.

              amitriptyline and trazodone both increase sedation. Use Caution/Monitor.

            • trazodone

              perphenazine and trazodone both increase sedation. Use Caution/Monitor.

            • triazolam

              triazolam and perphenazine both increase sedation. Use Caution/Monitor.

              triazolam and amitriptyline both increase sedation. Use Caution/Monitor.

            • triclofos

              triclofos and perphenazine both increase sedation. Use Caution/Monitor.

              triclofos and amitriptyline both increase sedation. Use Caution/Monitor.

            • trifluoperazine

              perphenazine and trifluoperazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              perphenazine and trifluoperazine both increase sedation. Use Caution/Monitor.

              trifluoperazine and amitriptyline both increase sedation. Use Caution/Monitor.

            • trihexyphenidyl

              trihexyphenidyl decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

              trihexyphenidyl and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. Potential for additive anticholinergic effects.

              perphenazine increases effects of trihexyphenidyl by pharmacodynamic synergism. Use Caution/Monitor. Potential for additive anticholinergic effects.

            • trimethoprim

              perphenazine and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

              amitriptyline and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

            • trimipramine

              perphenazine and trimipramine both increase sedation. Use Caution/Monitor.

              amitriptyline and trimipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

              amitriptyline and trimipramine both increase sedation. Use Caution/Monitor.

            • triprolidine

              triprolidine and perphenazine both increase sedation. Use Caution/Monitor.

              triprolidine and amitriptyline both increase sedation. Use Caution/Monitor.

            • tropisetron

              perphenazine and tropisetron both increase QTc interval. Modify Therapy/Monitor Closely.

              amitriptyline and tropisetron both increase QTc interval. Modify Therapy/Monitor Closely.

            • trospium chloride

              trospium chloride decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              trospium chloride and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              perphenazine increases effects of trospium chloride by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              trospium chloride decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

            • tucatinib

              tucatinib will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

            • 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.

            • valerian

              valerian and amitriptyline both increase sedation. Use Caution/Monitor.

            • vecuronium

              vecuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • venlafaxine

              venlafaxine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

              amitriptyline and venlafaxine both increase QTc interval. Modify Therapy/Monitor Closely.

              venlafaxine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • verapamil

              verapamil will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. The frequency and severity of amitriptyline adverse effects (sedation, anticholinergic effects and orthostatic hypotension) may be increased. Cardiac dysrhythmic effects may be additive.

            • vilazodone

              vilazodone, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • voclosporin

              voclosporin, amitriptyline. Either increases effects of the other by QTc interval. Use Caution/Monitor.

            • voriconazole

              perphenazine and voriconazole both increase QTc interval. Modify Therapy/Monitor Closely.

              voriconazole will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

              amitriptyline and voriconazole both increase QTc interval. Modify Therapy/Monitor Closely.

            • xylometazoline

              perphenazine, xylometazoline. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

              perphenazine increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              amitriptyline increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • yohimbine

              amitriptyline increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              perphenazine, yohimbine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.

              perphenazine increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ziconotide

              amitriptyline and ziconotide both increase sedation. Use Caution/Monitor.

              perphenazine and ziconotide both increase sedation. Use Caution/Monitor.

            • ziprasidone

              ziprasidone and amitriptyline both increase sedation. Use Caution/Monitor.

              perphenazine and ziprasidone both increase sedation. Use Caution/Monitor.

              perphenazine and ziprasidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

            • zolmitriptan

              zolmitriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

              zolmitriptan, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).

            • zolpidem

              perphenazine will increase the level or effect of zolpidem by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Additive effect of decreased alertness and psychomotor performance

            • zotepine

              perphenazine and zotepine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.

              perphenazine and zotepine both increase sedation. Use Caution/Monitor.

            Minor (165)

            • acarbose

              amitriptyline increases effects of acarbose by pharmacodynamic synergism. Minor/Significance Unknown.

            • amiodarone

              amiodarone will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • amitriptyline

              amitriptyline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              amitriptyline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • amobarbital

              amobarbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • amoxapine

              amoxapine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              amoxapine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • aripiprazole

              perphenazine will increase the level or effect of aripiprazole by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • armodafinil

              armodafinil will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • artemether/lumefantrine

              artemether/lumefantrine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • asenapine

              asenapine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • atropine

              perphenazine increases toxicity of atropine by unknown mechanism. Minor/Significance Unknown.

              amitriptyline increases levels of atropine by unknown mechanism. Minor/Significance Unknown.

            • atropine IV/IM

              perphenazine increases toxicity of atropine IV/IM by unknown mechanism. Minor/Significance Unknown.

              amitriptyline increases levels of atropine IV/IM by unknown mechanism. Minor/Significance Unknown.

            • bazedoxifene/conjugated estrogens

              bazedoxifene/conjugated estrogens, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • benazepril

              perphenazine increases effects of benazepril by unspecified interaction mechanism. Minor/Significance Unknown.

            • bortezomib

              bortezomib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • bosentan

              bosentan will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • brimonidine

              amitriptyline decreases effects of brimonidine by pharmacodynamic antagonism. Minor/Significance Unknown.

              brimonidine increases effects of perphenazine by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

            • budesonide

              budesonide will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • captopril

              perphenazine increases effects of captopril by unspecified interaction mechanism. Minor/Significance Unknown.

            • butabarbital

              butabarbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • butalbital

              butalbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • carbamazepine

              carbamazepine decreases levels of amitriptyline by increasing metabolism. Minor/Significance Unknown.

            • celecoxib

              celecoxib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • chasteberry

              chasteberry decreases effects of perphenazine by pharmacodynamic antagonism. Minor/Significance Unknown. (Theoretical interaction).

            • chloroquine

              chloroquine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              chloroquine increases levels of perphenazine by decreasing metabolism. Minor/Significance Unknown.

              chloroquine increases toxicity of perphenazine by QTc interval. Minor/Significance Unknown.

            • chlorpromazine

              amitriptyline, chlorpromazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              amitriptyline, chlorpromazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

              perphenazine will increase the level or effect of chlorpromazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • chlorpropamide

              amitriptyline increases effects of chlorpropamide by pharmacodynamic synergism. Minor/Significance Unknown.

            • cimetidine

              cimetidine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • clomipramine

              clomipramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              clomipramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • codeine

              perphenazine will increase the level or effect of codeine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              perphenazine decreases effects of codeine by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of codeine to active metabolite morphine.

            • conjugated estrogens

              conjugated estrogens, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • conjugated estrogens, vaginal

              conjugated estrogens, vaginal, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • cortisone

              cortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • darifenacin

              darifenacin will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • desflurane

              desflurane, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

            • desipramine

              desipramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              desipramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • dexamethasone

              dexamethasone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • dexfenfluramine

              perphenazine will increase the level or effect of dexfenfluramine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • dexmethylphenidate

              dexmethylphenidate increases effects of amitriptyline by decreasing metabolism. Minor/Significance Unknown.

            • DHEA, herbal

              DHEA, herbal will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • dextroamphetamine

              perphenazine will increase the level or effect of dextroamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • dextromethorphan

              perphenazine will increase the level or effect of dextromethorphan by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • diphenhydramine

              diphenhydramine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • donepezil

              perphenazine will increase the level or effect of donepezil by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • doxepin

              perphenazine will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              doxepin, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              doxepin, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • dronedarone

              dronedarone will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • duloxetine

              duloxetine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • enalapril

              perphenazine increases effects of enalapril by unspecified interaction mechanism. Minor/Significance Unknown.

            • encainide

              perphenazine will increase the level or effect of encainide by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • estradiol

              estradiol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • estrogens conjugated synthetic

              estrogens conjugated synthetic, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • estrogens esterified

              estrogens esterified, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens may inhibit hepatic metabolism of tricyclic antidepressants. However, interactions are not common.

            • estropipate

              estropipate, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • ethanol

              ethanol, amitriptyline. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive impairment of motor skills.

              ethanol, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.

            • ethinylestradiol

              ethinylestradiol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • eucalyptus

              perphenazine and eucalyptus both increase sedation. Minor/Significance Unknown.

            • etomidate

              etomidate, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

            • etravirine

              etravirine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • eucalyptus

              amitriptyline and eucalyptus both increase sedation. Minor/Significance Unknown.

            • felodipine

              felodipine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • fesoterodine

              perphenazine will increase the level or effect of fesoterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • fludrocortisone

              fludrocortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • fluphenazine

              amitriptyline, fluphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              amitriptyline, fluphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

              perphenazine will increase the level or effect of fluphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • fosinopril

              perphenazine increases effects of fosinopril by unspecified interaction mechanism. Minor/Significance Unknown.

            • glimepiride

              amitriptyline increases effects of glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.

            • galantamine

              perphenazine will increase the level or effect of galantamine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • glipizide

              amitriptyline increases effects of glipizide by pharmacodynamic synergism. Minor/Significance Unknown.

            • glyburide

              amitriptyline increases effects of glyburide by pharmacodynamic synergism. Minor/Significance Unknown.

            • griseofulvin

              griseofulvin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • haloperidol

              haloperidol will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • hydrocortisone

              hydrocortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • hydroxyprogesterone caproate

              hydroxyprogesterone caproate, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • imatinib

              imatinib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • imidapril

              perphenazine increases effects of imidapril by unspecified interaction mechanism. Minor/Significance Unknown.

            • imipramine

              imipramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              imipramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • insulin aspart

              amitriptyline increases effects of insulin aspart by pharmacodynamic synergism. Minor/Significance Unknown.

            • insulin detemir

              amitriptyline increases effects of insulin detemir by pharmacodynamic synergism. Minor/Significance Unknown.

            • insulin glargine

              amitriptyline increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.

            • insulin glulisine

              amitriptyline increases effects of insulin glulisine by pharmacodynamic synergism. Minor/Significance Unknown.

            • insulin lispro

              amitriptyline increases effects of insulin lispro by pharmacodynamic synergism. Minor/Significance Unknown.

            • insulin NPH

              amitriptyline increases effects of insulin NPH by pharmacodynamic synergism. Minor/Significance Unknown.

            • insulin regular human

              amitriptyline increases effects of insulin regular human by pharmacodynamic synergism. Minor/Significance Unknown.

            • isoniazid

              isoniazid will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • isoproterenol

              isoproterenol, amitriptyline. Mechanism: unknown. Minor/Significance Unknown. Risk of cardiac arrhythmias.

            • itraconazole

              itraconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ketamine

              ketamine, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

            • lapatinib

              lapatinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • lisinopril

              perphenazine increases effects of lisinopril by unspecified interaction mechanism. Minor/Significance Unknown.

            • lithium

              lithium, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Risk of neurotoxicity in geriatric pts. Multiple mechanisms involved.

            • lofepramine

              lofepramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              lofepramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • loratadine

              perphenazine will increase the level or effect of loratadine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • lumefantrine

              lumefantrine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • maprotiline

              maprotiline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              maprotiline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • maraviroc

              maraviroc will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • marijuana

              marijuana will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              marijuana will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • mestranol

              mestranol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • metyrapone

              perphenazine decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown.

            • metformin

              amitriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

            • methylprednisolone

              methylprednisolone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • metronidazole

              metronidazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • metyrapone

              amitriptyline decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown.

            • metyrosine

              metyrosine increases toxicity of perphenazine by pharmacodynamic synergism. Minor/Significance Unknown. Increased extrapyramidal symptoms.

            • miconazole vaginal

              miconazole vaginal will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • miglitol

              amitriptyline increases effects of miglitol by pharmacodynamic synergism. Minor/Significance Unknown.

            • modafinil

              modafinil will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • moexipril

              perphenazine increases effects of moexipril by unspecified interaction mechanism. Minor/Significance Unknown.

            • nateglinide

              amitriptyline increases effects of nateglinide by pharmacodynamic synergism. Minor/Significance Unknown.

            • nevirapine

              nevirapine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nifedipine

              nifedipine will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nilotinib

              nilotinib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              nilotinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • nortriptyline

              nortriptyline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              nortriptyline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • oxcarbazepine

              oxcarbazepine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

              oxcarbazepine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • oxybutynin

              oxybutynin increases toxicity of perphenazine by unspecified interaction mechanism. Minor/Significance Unknown.

            • oxybutynin topical

              oxybutynin topical increases toxicity of perphenazine by unspecified interaction mechanism. Minor/Significance Unknown.

            • oxybutynin transdermal

              oxybutynin transdermal increases toxicity of perphenazine by unspecified interaction mechanism. Minor/Significance Unknown.

            • oxycodone

              perphenazine decreases effects of oxycodone by decreasing metabolism. Minor/Significance Unknown. Decreased conversion of oxycodone to active metabolite morphine.

            • panax ginseng

              panax ginseng increases effects of amitriptyline by pharmacodynamic synergism. Minor/Significance Unknown.

            • parecoxib

              parecoxib will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              parecoxib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

            • pentobarbital

              pentobarbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • perhexiline

              perphenazine will increase the level or effect of perhexiline by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • perindopril

              perphenazine increases effects of perindopril by unspecified interaction mechanism. Minor/Significance Unknown.

            • perphenazine

              amitriptyline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              amitriptyline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • phenobarbital

              phenobarbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • pioglitazone

              amitriptyline increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

            • pleurisy root

              pleurisy root decreases effects of amitriptyline by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.

            • posaconazole

              posaconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • prednisone

              prednisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • primidone

              primidone, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • prochlorperazine

              amitriptyline, prochlorperazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              amitriptyline, prochlorperazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

              perphenazine will increase the level or effect of prochlorperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • progesterone micronized

              progesterone micronized, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • promazine

              perphenazine will increase the level or effect of promazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • promazine

              amitriptyline, promazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              amitriptyline, promazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • promethazine

              perphenazine will increase the level or effect of promethazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              amitriptyline, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              amitriptyline, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • propofol

              propofol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

            • protriptyline

              protriptyline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              protriptyline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • pyrimethamine

              pyrimethamine increases levels of perphenazine by decreasing metabolism. Minor/Significance Unknown.

            • quinacrine

              quinacrine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • quinapril

              perphenazine increases effects of quinapril by unspecified interaction mechanism. Minor/Significance Unknown.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ramipril

              perphenazine increases effects of ramipril by unspecified interaction mechanism. Minor/Significance Unknown.

            • ranolazine

              ranolazine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • repaglinide

              amitriptyline increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

            • risperidone

              perphenazine will increase the level or effect of risperidone by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • ritonavir

              ritonavir will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • rosiglitazone

              amitriptyline increases effects of rosiglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

            • rufinamide

              rufinamide will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • sage

              perphenazine and sage both increase sedation. Minor/Significance Unknown.

              amitriptyline and sage both increase sedation. Minor/Significance Unknown.

            • saxagliptin

              amitriptyline increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

            • sertraline

              sertraline will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • secobarbital

              secobarbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

            • sevoflurane

              sevoflurane, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

            • sitagliptin

              amitriptyline increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

            • sulfamethoxazole

              sulfamethoxazole decreases levels of amitriptyline by unspecified interaction mechanism. Minor/Significance Unknown.

            • thioridazine

              amitriptyline, thioridazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              amitriptyline, thioridazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

              thioridazine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • tipranavir

              tipranavir will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • tolazamide

              amitriptyline increases effects of tolazamide by pharmacodynamic synergism. Minor/Significance Unknown.

            • tolbutamide

              amitriptyline increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

            • tolterodine

              perphenazine will increase the level or effect of tolterodine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • trandolapril

              perphenazine increases effects of trandolapril by unspecified interaction mechanism. Minor/Significance Unknown.

            • trazodone

              trazodone, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.

              trazodone, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

            • trifluoperazine

              perphenazine will increase the level or effect of trifluoperazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

              amitriptyline, trifluoperazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              amitriptyline, trifluoperazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • trimipramine

              trimipramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              trimipramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • vasopressin

              amitriptyline increases effects of vasopressin by pharmacodynamic synergism. Minor/Significance Unknown.

            • tropisetron

              perphenazine will increase the level or effect of tropisetron by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • verapamil

              verapamil will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

              verapamil increases levels of amitriptyline by decreasing metabolism. Minor/Significance Unknown.

            Frequency Not Defined

            Sedation

            Fatigue

            Constipation

            Dry mouth

            Lethargy

            Weakness

            Anticholinergic effects

            Blurred vision

            Lens opacities

            Orthostatic hypotension

            Agitation

            Anxiety

            Headache

            Insomnia

            Nausea/vomiting

            Sweating

            Orthostatic hypotension

            ECG changes

            Tachycardia

            Confusion

            EPS

            Dizziness

            Paresthesia

            Rash

            Increased LFTs

            Sexual dysfunction

            Tinnitus

            Seizure

            Agranulocytosis

            Thrombocytopenia

            Eosinophilia

            Leukopenia

            SIADH

            Antipsychotic side effects

            Poikilothermia

            Decreased gag reflex

            Weight gain

            Amenorrhea

            Post Marketing Reports

            Neuroleptic malignant syndrome

            Serotonin syndrome

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            Warnings

            Black Box Warnings

            Children & Antidepressants

            • In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (< 24 years of age) taking antidepressants for major depressive disorders and other psychiatric illnesses. This increase was not seen in patients >24 years of age. A slight decrease in suicidal thinking was seen in adults >65 years. Risks must be weighed in children and young adults against the benefits of taking antidepressants. Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies. This should be done during the initial 1-2 months of therapy and dosage adjustments. The patient’s family should communicate to the healthcare provider any abrupt changes in behavior. Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy. This drug is not approved for use in pediatric patients.

            Antipsychotics & Dementia

            • Patients with dementia-related psychosis that are treated with antipsychotic drugs are at an increased risk of death as shown in short-term controlled trials. The deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. This drug is not approved for the treatment of patients with dementia-related psychosis (See WARNINGS in package insert).

            Contraindications

            Tricyclic Antidepressant (amitriptyline): hypersensitivity, severe cardiovascular disorder, narrow angle glaucoma, within 14 days of MAOIs (risk of serotonin syndrome), any drugs or conditions that prolong QT interval, acute recovery post-MI

            Antipsychotic (perphenazine): hypersensitivity, CNS depression, neuroleptic malignant syndrome, poorly controlled seizure disorder, subcortical braine damage, coma, severe obtundation, high dose CNS depressants, blood dyscrasia, myelosuppression, liver damage

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            Pregnancy & Lactation

            Pregnancy Category: D

            Lactation: excreted in breast milk; not recommended

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Amitriptyline: Antidepressant; neurotransmitter (especially norepinephrine and serotonin) reuptake inhibitor; elicits anticholinergic effects

            Perphenazine: Antipsychotic agent; elicits moderate anticholinergic effects, weak to moderate sedative effects, strong extrapyramidal effects, and strong antiemetic activity

            Pharmacokinetics

            Amitriptyline

            • Onset of action: 6 weeks
            • Half-life: 9-27 hr
            • Peak serum time: 4 hr
            • Metabolism: Hepatic (CYP2C19, CYP3A4)
            • Excretion: Urine (25-50%); bile (small amounts)

            Perphenazine

            • Half-life: 9-12 hr
            • Peak plasma time: 1-3 hr; 2-4 hr (metabolite)
            • Metabolism: Hepatic P450 enzyme (CYP2D6)
            • Excretion: Urine; feces
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            Images

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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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            Code Definition
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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.