death, more likely w/thioridazine than other phenothiazines. Interaction more likely in certain predisposed pts. only.phendimetrazineamitriptyline increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.phenelzinephenelzine, 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).phenobarbitalphenobarbital 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.phentermineperphenazine 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.phenylephrineperphenazine 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 POperphenazine 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 POamitriptyline increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .phenylephrine ophthalmicamitriptyline, 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.phenytoinphenytoin 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.pholcodineperphenazine and pholcodine both increase sedation. Use Caution/Monitor.amitriptyline and pholcodine both increase sedation. Use Caution/Monitor.physostigminephysostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.pimozideperphenazine 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.pilocarpinepilocarpine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.pimozidepimozide and amitriptyline both increase sedation. Use Caution/Monitor.pirbuterolamitriptyline 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.ponatinibponatinib increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.porfimerperphenazine, porfimer. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced photosensitivity.posaconazoleperphenazine and posaconazole both increase QTc interval. Modify Therapy/Monitor Closely.amitriptyline and posaconazole both increase QTc interval. Modify Therapy/Monitor Closely.pralidoximeperphenazine 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.pregabalinpregabalin, 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.primaquineprimaquine and perphenazine both increase QTc interval. Use Caution/Monitor.primidoneprimidone and perphenazine both increase sedation. Use Caution/Monitor.primidone will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.primidone and amitriptyline both increase sedation. Use Caution/Monitor.primidone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.procarbazineprocarbazine, 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).prochlorperazineprochlorperazine and amitriptyline both increase QTc interval. Use Caution/Monitor.prochlorperazine and amitriptyline both increase sedation. Use Caution/Monitor.prochlorperazineperphenazine and prochlorperazine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.perphenazine and prochlorperazine both increase sedation. Use Caution/Monitor.promethazinepromethazine 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.propafenoneperphenazine 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.propanthelinepropantheline and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.propanthelinepropantheline 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.propofolpropofol and amitriptyline both increase sedation. Use Caution/Monitor.propofol and perphenazine both increase sedation. Use Caution/Monitor.propranololperphenazine will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.propylhexedrineamitriptyline increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.propylhexedrineperphenazine 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.protriptylineamitriptyline 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.pseudoephedrineperphenazine, 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.pyridostigminepyridostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.quazepamquazepam and perphenazine both increase sedation. Use Caution/Monitor.quazepam and amitriptyline both increase sedation. Use Caution/Monitor.quercetinquercetin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.quetiapineperphenazine 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.quetiapinequetiapine 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.quinidinequinidine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.quinineperphenazine and quinine both increase QTc interval. Use Caution/Monitor.amitriptyline and quinine both increase QTc interval. Use Caution/Monitor.ramelteonperphenazine and ramelteon both increase sedation. Use Caution/Monitor.amitriptyline and ramelteon both increase sedation. Use Caution/Monitor.ranolazineamitriptyline and ranolazine both increase QTc interval. Modify Therapy/Monitor Closely.perphenazine and ranolazine both increase QTc interval. Modify Therapy/Monitor Closely.rapacuroniumperphenazine 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.remifentanilamitriptyline, remifentanil. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. May also increase risk of serotonin syndrome.remimazolamremimazolam, 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.remimazolamremimazolam, 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.rifabutinrifabutin 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.rifampinrifampin 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.rifapentinerifapentine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.rilpivirinerilpivirine 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.rimabotulinumtoxinBperphenazine, 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.risperidoneamitriptyline 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.ritonavirritonavir 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.rizatriptanrizatriptan, 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).rivastigminerivastigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.rizatriptanrizatriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.rocuroniumrocuronium 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.rolapitantrolapitant 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.romidepsinperphenazine and romidepsin both increase QTc interval. Modify Therapy/Monitor Closely.amitriptyline and romidepsin both increase QTc interval. Modify Therapy/Monitor Closely.salmeterolperphenazine 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.SAMeamitriptyline and SAMe both increase serotonin levels. Modify Therapy/Monitor Closely.scopolaminescopolamine 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.