neuron.pitolisantSerious - Use Alternative (1)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.pleurisy rootMinor (1)pleurisy root decreases effects of amitriptyline by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.ponatinibMonitor Closely (1)ponatinib increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.porfimerMonitor Closely (1)perphenazine, porfimer. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Enhanced photosensitivity.posaconazoleMonitor Closely (2)perphenazine and posaconazole both increase QTc interval. Modify Therapy/Monitor Closely. amitriptyline and posaconazole both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)posaconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.pralidoximeMonitor Closely (4)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.pramipexoleSerious - Use Alternative (1)perphenazine decreases effects of pramipexole by pharmacodynamic antagonism. Contraindicated.prednisoneMinor (1)prednisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.pregabalinMonitor Closely (1)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.primaquineMonitor Closely (1)primaquine and perphenazine both increase QTc interval. Use Caution/Monitor.primidoneMonitor Closely (4)primidone will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. primidone and perphenazine both increase sedation. 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.Minor (1)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.procainamideContraindicated (2)amitriptyline and procainamide both increase QTc interval. Contraindicated. perphenazine and procainamide both increase QTc interval. Contraindicated.procarbazineContraindicated (1)procarbazine and amitriptyline both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI use.Monitor Closely (2)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). procarbazine, perphenazine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Excessive sedation.prochlorperazineMonitor Closely (4)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.Minor (3)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.Serious - Use Alternative (1)perphenazine and prochlorperazine both increase QTc interval. Avoid or Use Alternate Drug.progesterone micronizedMinor (1)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.promazineSerious - Use Alternative (2)promazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug. perphenazine and promazine both increase QTc interval. Avoid or Use Alternate Drug.Minor (3)perphenazine will increase the level or effect of promazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown. 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.promethazineMonitor Closely (5)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.Minor (3)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.Serious - Use Alternative (1)perphenazine and promethazine both increase QTc interval. Avoid or Use Alternate Drug.propafenoneMonitor Closely (2)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.propanthelineMonitor Closely (4)propantheline decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. perphenazine increases effects of propantheline by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. propantheline and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. propantheline decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.propofolMonitor Closely (2)propofol and amitriptyline both increase sedation. Use Caution/Monitor. propofol and perphenazine both increase sedation. Use Caution/Monitor.Minor (1)propofol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.propranololMonitor Closely (1)perphenazine will increase the level or effect of propranolol by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.propylhexedrineMonitor Closely (3)amitriptyline increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. 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.Serious - Use Alternative (1)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.protriptylineMonitor Closely (3)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.Serious - Use Alternative (3)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.Minor (2)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.pseudoephedrineMonitor Closely (1)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.Serious - Use Alternative (1)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.pyridostigmineMonitor Closely (1)pyridostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.pyrimethamineMinor (1)pyrimethamine increases levels of perphenazine by decreasing metabolism. Minor/Significance Unknown.quazepamMonitor Closely (2)quazepam and perphenazine both increase sedation. Use Caution/Monitor. quazepam and amitriptyline both increase sedation. Use Caution/Monitor.quercetinMonitor Closely (1)quercetin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.quetiapineMonitor Closely (4)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. quetiapine and amitriptyline both increase sedation. Use Caution/Monitor. perphenazine and quetiapine both increase sedation. Use Caution/Monitor. perphenazine and quetiapine both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.quinacrineMinor (1)quinacrine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.quinaprilMinor (1)perphenazine increases effects of quinapril by unspecified interaction mechanism. Minor/Significance Unknown.quinidineContraindicated (2)perphenazine and quinidine both increase QTc interval. Contraindicated. quinidine and amitriptyline both increase QTc interval. Contraindicated.Monitor Closely (1)quinidine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (2)quinidine, perphenazine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Additive cardiac effects. quinidine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.quinineMonitor Closely (2)perphenazine and quinine both increase QTc interval. Use Caution/Monitor. amitriptyline and quinine both increase QTc interval. Use Caution/Monitor.quinupristin/dalfopristinMinor (1)quinupristin/dalfopristin will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.ramelteonMonitor Closely (2)perphenazine and ramelteon both increase sedation. Use Caution/Monitor. amitriptyline and ramelteon both increase sedation. Use Caution/Monitor.ramiprilMinor (1)perphenazine increases effects of ramipril by unspecified interaction mechanism. Minor/Significance Unknown.ranolazineMonitor Closely (2)amitriptyline and ranolazine both increase QTc interval. Modify Therapy/Monitor Closely. perphenazine and ranolazine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)ranolazine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.Minor (1)ranolazine will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.rapacuroniumMonitor Closely (4)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.rasagilineSerious - Use Alternative (1)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.remifentanilMonitor Closely (1)amitriptyline, remifentanil. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. May also increase risk of serotonin syndrome.remimazolamMonitor Closely (2)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. 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.repaglinideMinor (1)amitriptyline increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.ribociclibSerious - Use Alternative (2)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.rifabutinMonitor Closely (2)rifabutin decreases levels of amitriptyline by increasing metabolism. Use Caution/Monitor. rifabutin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.rifampinMonitor Closely (3)rifampin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. 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.rifapentineMonitor Closely (1)rifapentine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.rilpivirineMonitor Closely (1)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.rimabotulinumtoxinBMonitor Closely (1)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.risperidoneMonitor Closely (5)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.