Use Caution/Monitor.istradefyllineistradefylline 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.itraconazoleitraconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.itraconazole and amitriptyline both increase QTc interval. Use Caution/Monitor.ivacaftorivacaftor 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.ketamineketamine and amitriptyline both increase sedation. Use Caution/Monitor.ketamine and perphenazine both increase sedation. Use Caution/Monitor.ketoconazoleketoconazole 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, ophthalmicperphenazine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.ketotifen, ophthalmicamitriptyline and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.L-tryptophanamitriptyline and L-tryptophan both increase serotonin levels. Modify Therapy/Monitor Closely.lapatinibamitriptyline and lapatinib both increase QTc interval. Modify Therapy/Monitor Closely.perphenazine and lapatinib both increase QTc interval. Modify Therapy/Monitor Closely.lasmiditanlasmiditan, 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.lemborexantlemborexant, 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.letermovirletermovir increases levels of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.levalbuterolperphenazine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.levalbuterolamitriptyline increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.levofloxacinamitriptyline and levofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.perphenazine and levofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.levoketoconazolelevoketoconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.levoketoconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.levomilnacipranlevomilnacipran, 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).levorphanollevorphanol and amitriptyline both increase sedation. Use Caution/Monitor.levorphanol and perphenazine both increase sedation. Use Caution/Monitor.levothyroxinelevothyroxine increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.linezolidlinezolid, 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).liothyronineliothyronine increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.liotrixliotrix increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.liraglutideperphenazine, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase or decrease glucose levels, monitor therapy closely when these agents are concurrently administered.lisdexamfetamineamitriptyline 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.lithiumlithium and amitriptyline both increase QTc interval. Use Caution/Monitor.lithium and perphenazine both increase QTc interval. Use Caution/Monitor.lithium, perphenazine. unspecified interaction mechanism. Use Caution/Monitor. Serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotics may enhance serotonergic effect of serotonin modulators, which may result in serotonin syndrome. Monitor for evidence of serotonin toxicity (eg, mental status changes, autonomic instability, and neuromuscular hyperactivity) or neuroleptic malignant syndrome (eg, hyperthermia, muscle rigidity, autonomic dysfunction).amitriptyline and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.lithium, perphenazine. Other (see comment). Use Caution/Monitor. Comment: Risk of neurotoxicity. Multiple mechanisms involved.lofepramineperphenazine 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.lofexidineperphenazine 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.loprazolamloprazolam and amitriptyline both increase sedation. Use Caution/Monitor.loprazolam and perphenazine both increase sedation. Use Caution/Monitor.loratadineloratadine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.lorazepamlorazepam and perphenazine both increase sedation. Use Caution/Monitor.lorazepamlorazepam and amitriptyline both increase sedation. Use Caution/Monitor.lorcaserinlorcaserin 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).lormetazepamlormetazepam and perphenazine both increase sedation. Use Caution/Monitor.lormetazepam and amitriptyline both increase sedation. Use Caution/Monitor.loxapineloxapine 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 inhaledloxapine 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.lsdamitriptyline and lsd both increase serotonin levels. Modify Therapy/Monitor Closely.lumefantrinelumefantrine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.lurasidonelurasidone, 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.maprotilineperphenazine 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.maravirocmaraviroc, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.marijuanaperphenazine and marijuana both increase sedation. Use Caution/Monitor.marijuanaamitriptyline and marijuana both increase sedation. Use Caution/Monitor.mavacamtenamitriptyline 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. meclizinemeclizine 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.melatoninperphenazine and melatonin both increase sedation. Use Caution/Monitor.amitriptyline and melatonin both increase sedation. Use Caution/Monitor.meperidinemeperidine 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.meprobamateamitriptyline and meprobamate both increase sedation. Use Caution/Monitor.perphenazine and meprobamate both increase sedation. Use Caution/Monitor.metaproterenolperphenazine 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.metaxalonemetaxalone and amitriptyline both increase sedation. Use Caution/Monitor.metaxalone and perphenazine both increase sedation. Use Caution/Monitor.metforminperphenazine 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.methadoneamitriptyline and methadone both increase QTc interval. Modify Therapy/Monitor Closely.methadone and amitriptyline both increase sedation. Use Caution/Monitor.methadoneperphenazine 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).methamphetamineperphenazine, 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.methocarbamolmethocarbamol and perphenazine both increase sedation. Use Caution/Monitor.methocarbamol and amitriptyline both increase sedation. Use Caution/Monitor.methoxsalenmethoxsalen, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Additive photosensitizing effects.methscopolaminemethscopolamine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.methscopolaminemethscopolamine 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.methylenedioxymethamphetamineperphenazine, 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.methylergonovinemethylergonovine, 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).methylphenidateamitriptyline, 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.methylphenidateperphenazine, 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 transdermalmethylphenidate 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. metoclopramideperphenazine and metoclopramide both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.metoprololperphenazine will increase