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.phendimetrazineMonitor Closely (1)protriptyline increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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.phenelzineContraindicated (1)phenelzine and protriptyline both increase serotonin levels. Contraindicated.phenobarbitalMonitor Closely (1)phenobarbital and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)phenobarbital, protriptyline. 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.phentermineMonitor Closely (1)protriptyline increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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.phenylephrineMonitor Closely (1)protriptyline increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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 ophthalmicMonitor Closely (1)protriptyline, 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.phenylephrine POMonitor Closely (1)protriptyline increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .Serious - Use Alternative (1)protriptyline, 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.pholcodineMonitor Closely (1)protriptyline and pholcodine both increase sedation. Use Caution/Monitor.physostigmineMonitor Closely (1)physostigmine increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.pilocarpineMonitor Closely (1)pilocarpine increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.pimozideContraindicated (1)protriptyline and pimozide both increase QTc interval. Contraindicated.Monitor Closely (1)pimozide and protriptyline both increase sedation. Use Caution/Monitor.pioglitazoneMinor (1)protriptyline increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.pirbuterolMonitor Closely (1)protriptyline increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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.pitolisantSerious - Use Alternative (1)protriptyline 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 protriptyline by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.posaconazoleMonitor Closely (1)protriptyline and posaconazole both increase QTc interval. Modify Therapy/Monitor Closely.pralidoximeMonitor Closely (1)pralidoxime and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.pregabalinMonitor Closely (1)pregabalin, protriptyline. 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.primidoneMonitor Closely (1)primidone and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)primidone, protriptyline. 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 (1)protriptyline and procainamide both increase QTc interval. Contraindicated.procarbazineContraindicated (1)procarbazine and protriptyline both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI use.prochlorperazineMonitor Closely (2)prochlorperazine and protriptyline both increase QTc interval. Use Caution/Monitor. prochlorperazine and protriptyline both increase sedation. Use Caution/Monitor.Minor (2)protriptyline, prochlorperazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects. protriptyline, prochlorperazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.progesterone micronizedMinor (1)progesterone micronized, protriptyline. 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 (1)promazine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)protriptyline, promazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects. protriptyline, promazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.promethazineMonitor Closely (2)promethazine and protriptyline both increase QTc interval. Use Caution/Monitor. promethazine and protriptyline both increase sedation. Use Caution/Monitor.Minor (2)protriptyline, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects. protriptyline, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.propanthelineMonitor Closely (1)propantheline and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.propofolMonitor Closely (1)propofol and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)propofol, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.propylhexedrineMonitor Closely (1)protriptyline increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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.pseudoephedrineSerious - Use Alternative (1)protriptyline 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 protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.quazepamMonitor Closely (1)quazepam and protriptyline both increase sedation. Use Caution/Monitor.quetiapineMonitor Closely (2)quetiapine and protriptyline both increase sedation. Use Caution/Monitor. quetiapine, protriptyline. 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.quinidineContraindicated (1)quinidine and protriptyline both increase QTc interval. Contraindicated.quinineMonitor Closely (1)protriptyline and quinine both increase QTc interval. Use Caution/Monitor.ramelteonMonitor Closely (1)protriptyline and ramelteon both increase sedation. Use Caution/Monitor.ranolazineMonitor Closely (1)protriptyline and ranolazine both increase QTc interval. Modify Therapy/Monitor Closely.rapacuroniumMonitor Closely (1)rapacuronium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.rasagilineSerious - Use Alternative (1)rasagiline and protriptyline 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.remimazolamMonitor Closely (1)remimazolam, protriptyline. 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)protriptyline increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.ribociclibSerious - Use Alternative (1)ribociclib increases toxicity of protriptyline by QTc interval. Avoid or Use Alternate Drug.rifabutinMonitor Closely (1)rifabutin decreases levels of protriptyline by increasing metabolism. Use Caution/Monitor.rilpivirineMonitor Closely (1)rilpivirine increases toxicity of protriptyline by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsade de Pointes.risperidoneMonitor Closely (2)protriptyline and risperidone both increase QTc interval. Modify Therapy/Monitor Closely. risperidone and protriptyline both increase sedation. Use Caution/Monitor.rivastigmineMonitor Closely (1)rivastigmine increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.rizatriptanMonitor Closely (1)rizatriptan and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.rocuroniumMonitor Closely (1)rocuronium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.rolapitantMonitor Closely (1)rolapitant will increase the level or effect of protriptyline 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.romidepsinMonitor Closely (1)protriptyline and romidepsin both increase QTc interval. Modify Therapy/Monitor Closely.rosiglitazoneMinor (1)protriptyline increases effects of rosiglitazone by pharmacodynamic synergism. Minor/Significance Unknown.safinamideContraindicated (1)protriptyline, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.sageMinor (1)protriptyline and sage both increase sedation. Minor/Significance Unknown.salmeterolMonitor Closely (1)protriptyline increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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.SAMeMonitor Closely (1)protriptyline and SAMe both increase serotonin levels. Modify Therapy/Monitor Closely.saxagliptinMinor (1)protriptyline increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.scopolamineMonitor Closely (1)scopolamine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.scullcapMonitor Closely (1)protriptyline and scullcap both increase sedation. Use Caution/Monitor.secobarbitalMonitor Closely (1)secobarbital and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)secobarbital, protriptyline. 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.selegilineContraindicated (1)selegiline and protriptyline both increase serotonin levels. Contraindicated. Concurrent use or use within 14 days of selegiline treatment is contraindicatedselegiline transdermalSerious - Use Alternative (1)selegiline transdermal and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.selinexorSerious - Use Alternative (1)selinexor, protriptyline. 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.selpercatinibMonitor Closely (1)selpercatinib increases toxicity of protriptyline by QTc interval. Use Caution/Monitor.serdexmethylphenidate/dexmethylphenidateSerious - Use Alternative (1)protriptyline, serdexmethylphenidate/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.Minor (1)serdexmethylphenidate/dexmethylphenidate increases effects of protriptyline by decreasing metabolism. Minor/Significance Unknown.sertralineSerious - Use Alternative (2)sertraline and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug. sertraline and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.sevofluraneMonitor Closely (2)sevoflurane and protriptyline both increase sedation. Use Caution/Monitor. sevoflurane and protriptyline both increase QTc interval. Use Caution/Monitor.Minor (1)sevoflurane, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.shepherd's purseMonitor Closely (1)protriptyline and shepherd's purse both increase sedation. Use Caution/Monitor.sitagliptinMinor (1)protriptyline increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.sodium oxybateSerious - Use Alternative (1)protriptyline, 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 sulfate/?magnesium sulfate/potassium chlorideMonitor Closely (1)sodium sulfate/?magnesium sulfate/potassium chloride increases effects of protriptyline 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 chloride/magnesium sulfate/polyethylene glycolMonitor Closely (1)protriptyline, sodium sulfate/potassium chloride/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.sodium sulfate/potassium sulfate/magnesium sulfateMonitor Closely (1)sodium sulfate/potassium sulfate/magnesium sulfate increases effects of protriptyline 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.solifenacinMonitor Closely (2)solifenacin and protriptyline both increase QTc interval. Use Caution/Monitor. solifenacin and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.sorafenibMonitor Closely (1)sorafenib and protriptyline both increase QTc interval. Use Caution/Monitor.sotalolContraindicated (1)protriptyline and sotalol both increase QTc interval. Contraindicated.St John's WortSerious - Use Alternative (1)protriptyline and St John's Wort both increase serotonin levels. Avoid or Use Alternate Drug.stiripentolMonitor Closely (1)stiripentol, protriptyline. 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.succinylcholineMonitor Closely (1)succinylcholine increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.sufentanilMonitor Closely (1)sufentanil and protriptyline both increase sedation. Use Caution/Monitor.sufentanil SLMonitor Closely (1)sufentanil SL, protriptyline. 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