hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.lorazepamMonitor Closely (2)lorazepam and perphenazine both increase sedation. Use Caution/Monitor. lorazepam and amitriptyline both increase sedation. Use Caution/Monitor.lorcaserinMonitor Closely (3)lorcaserin will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. lorcaserin will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. lorcaserin, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).Serious - Use Alternative (2)amitriptyline and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug. perphenazine and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.lormetazepamMonitor Closely (2)lormetazepam and perphenazine both increase sedation. Use Caution/Monitor. lormetazepam and amitriptyline both increase sedation. Use Caution/Monitor.loxapineMonitor Closely (3)loxapine and perphenazine both increase sedation. Use Caution/Monitor. loxapine and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. loxapine and amitriptyline both increase sedation. Use Caution/Monitor.loxapine inhaledMonitor Closely (3)loxapine inhaled and perphenazine both increase sedation. Use Caution/Monitor. loxapine inhaled and perphenazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor. loxapine inhaled and amitriptyline both increase sedation. Use Caution/Monitor.lsdMonitor Closely (1)amitriptyline and lsd both increase serotonin levels. Modify Therapy/Monitor Closely.lumefantrineMonitor Closely (1)lumefantrine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (2)perphenazine and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)lumefantrine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.lurasidoneMonitor Closely (3)lurasidone, amitriptyline. Either increases toxicity of the other by sedation. Use Caution/Monitor. Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity. lurasidone, perphenazine. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity. lurasidone increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of hypotension with concurrent use. Monitor blood pressure and adjust dose of antihypertensive agent as needed.macimorelinSerious - Use Alternative (2)macimorelin and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug. Macimorelin causes an increase of ~11 msec in the corrected QT interval. Avoid coadministration with drugs that prolong QT interval, which could increase risk for developing torsade de pointes-type ventricular tachycardia. Allow sufficient washout time of drugs that are known to prolong the QT interval before administering macimorelin. macimorelin and perphenazine both increase QTc interval. Avoid or Use Alternate Drug. Macimorelin causes an increase of ~11 msec in the corrected QT interval. Avoid coadministration with drugs that prolong QT interval, which could increase risk for developing torsade de pointes-type ventricular tachycardia. Allow sufficient washout time of drugs that are known to prolong the QT interval before administering macimorelin.maprotilineMonitor Closely (3)perphenazine and maprotiline both increase sedation. Use Caution/Monitor. amitriptyline and maprotiline both increase sedation. Use Caution/Monitor. amitriptyline and maprotiline both decrease cholinergic effects/transmission. Use Caution/Monitor.Serious - Use Alternative (3)amitriptyline and maprotiline both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and maprotiline both increase serotonin levels. Avoid or Use Alternate Drug. perphenazine and maprotiline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)maprotiline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects. maprotiline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.maravirocMonitor Closely (1)maraviroc, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.Minor (1)maraviroc will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.marijuanaMonitor Closely (2)perphenazine and marijuana both increase sedation. Use Caution/Monitor. amitriptyline and marijuana both increase sedation. Use Caution/Monitor.Minor (2)marijuana will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown. marijuana will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.mavacamtenMonitor Closely (1)amitriptyline will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose. meclizineMonitor Closely (4)meclizine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. meclizine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor. perphenazine increases effects of meclizine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. meclizine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.mefloquineSerious - Use Alternative (1)mefloquine increases toxicity of amitriptyline by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.melatoninMonitor Closely (2)perphenazine and melatonin both increase sedation. Use Caution/Monitor. amitriptyline and melatonin both increase sedation. Use Caution/Monitor.meperidineMonitor Closely (3)meperidine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction). meperidine and perphenazine both increase sedation. Use Caution/Monitor. meperidine and amitriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline and meperidine both increase serotonin levels. Avoid or Use Alternate Drug.meprobamateMonitor Closely (2)amitriptyline and meprobamate both increase sedation. Use Caution/Monitor. perphenazine and meprobamate both increase sedation. Use Caution/Monitor.mestranolMinor (1)mestranol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.metaproterenolMonitor Closely (2)perphenazine increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. amitriptyline increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, metaproterenol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.metaxaloneMonitor Closely (2)metaxalone and amitriptyline both increase sedation. Use Caution/Monitor. metaxalone and perphenazine both increase sedation. Use Caution/Monitor.metforminMonitor Closely (1)perphenazine decreases effects of metformin by pharmacodynamic antagonism. Use Caution/Monitor. Patient should be closely observed for loss of blood glucose control; when drugs are withdrawn from a patient receiving metformin, patient should be observed closely for hypoglycemia.Minor (1)amitriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.methadoneMonitor Closely (5)perphenazine and methadone both increase QTc interval. Modify Therapy/Monitor Closely. methadone, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction). methadone and perphenazine both increase sedation. Use Caution/Monitor. amitriptyline and methadone both increase QTc interval. Modify Therapy/Monitor Closely. methadone and amitriptyline both increase sedation. Use Caution/Monitor.methamphetamineMonitor Closely (4)perphenazine, methamphetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only. perphenazine increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. amitriptyline increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. perphenazine will increase the level or effect of methamphetamine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, methamphetamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.methocarbamolMonitor Closely (2)methocarbamol and perphenazine both increase sedation. Use Caution/Monitor. methocarbamol and amitriptyline both increase sedation. Use Caution/Monitor.methoxsalenMonitor Closely (1)methoxsalen, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive photosensitizing effects.methscopolamineMonitor Closely (4)methscopolamine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. perphenazine increases effects of methscopolamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. methscopolamine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. methscopolamine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.methyl aminolevulinateSerious - Use Alternative (1)perphenazine, methyl aminolevulinate. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Each drug may increase the photosensitizing effect of the other.methyldopaSerious - Use Alternative (1)perphenazine decreases effects of methyldopa by pharmacodynamic antagonism. Contraindicated.methylene blueSerious - Use Alternative (1)methylene blue and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.methylenedioxymethamphetamineMonitor Closely (3)perphenazine, methylenedioxymethamphetamine. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only. perphenazine increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. amitriptyline increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, methylenedioxymethamphetamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.methylergonovineMonitor Closely (1)methylergonovine, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).methylphenidateMonitor Closely (3)amitriptyline, methylphenidate. Other (see comment). Use Caution/Monitor. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron. perphenazine, methylphenidate. Mechanism: unknown. Use Caution/Monitor. Risk of cardiac arrhythmia or sudden death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only. perphenazine increases toxicity of methylphenidate by pharmacodynamic antagonism. Use Caution/Monitor. Closely monitor for signs of altered clinical response to either methylphenidate or an antipsychotic when using these drugs in combination.methylphenidate transdermalMonitor Closely (1)methylphenidate transdermal will increase the level or effect of amitriptyline by decreasing elimination. Modify Therapy/Monitor Closely. Consider decreasing the dose of these drugs when given coadministered with methylphenidate. Monitor for drug toxiticities when initiating or discontinuing methylphenidate. methylprednisoloneMinor (1)methylprednisolone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.metoclopramideMonitor Closely (1)perphenazine and metoclopramide both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.metoclopramide intranasalSerious - Use Alternative (3)perphenazine, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient. perphenazine increases toxicity of metoclopramide intranasal by pharmacodynamic synergism. Avoid or Use Alternate Drug. Potential for additive effects, including increased frequency and severity of tardive dyskinesia, other extrapyramidal symptoms, and neuroleptic malignant syndrome. amitriptyline, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.metoprololMonitor Closely (1)perphenazine will increase the level or effect of metoprolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.metrizamideContraindicated (1)perphenazine, metrizamide. Mechanism: unknown. Contraindicated. Risk of seizure. D/C phenothiazine 24h before admin. of metrizamide.metronidazoleMinor (1)metronidazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.metyraponeMinor (2)amitriptyline decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown. perphenazine decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown.metyrosineMinor (1)metyrosine increases toxicity of perphenazine by pharmacodynamic synergism. Minor/Significance Unknown. Increased extrapyramidal symptoms.mexiletineMonitor Closely (1)perphenazine will increase the level or effect of mexiletine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.miconazole vaginalMinor (1)miconazole vaginal will increase the level or effect