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.primidoneMonitor Closely (3)primidone will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. primidone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. primidone and amitriptyline both increase sedation. Use Caution/Monitor.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 (1)amitriptyline 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.prochlorperazineMonitor Closely (2)prochlorperazine and amitriptyline both increase QTc interval. Use Caution/Monitor. prochlorperazine and amitriptyline both increase sedation. Use Caution/Monitor.Minor (2)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.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 (1)promazine and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)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 (2)promethazine and amitriptyline both increase QTc interval. Use Caution/Monitor. promethazine and amitriptyline both increase sedation. Use Caution/Monitor.Minor (2)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.propanthelineMonitor Closely (1)propantheline and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.propofolMonitor Closely (1)propofol and amitriptyline both increase sedation. Use Caution/Monitor.Minor (1)propofol, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.propylhexedrineMonitor Closely (1)amitriptyline increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.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 (2)amitriptyline and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. amitriptyline and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)amitriptyline and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.pseudoephedrineSerious - 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.quazepamMonitor Closely (1)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 (2)quetiapine 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.quinidineContraindicated (1)quinidine and amitriptyline both increase QTc interval. Contraindicated.Serious - Use Alternative (1)quinidine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.quinineMonitor Closely (1)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 (1)amitriptyline and ramelteon both increase sedation. Use Caution/Monitor.ranolazineMonitor Closely (1)amitriptyline 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.rapacuroniumMonitor Closely (1)rapacuronium and amitriptyline both decrease cholinergic effects/transmission. 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 (1)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.repaglinideMinor (1)amitriptyline increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.ribociclibSerious - Use Alternative (1)ribociclib increases toxicity of amitriptyline 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.risperidoneMonitor Closely (2)amitriptyline and risperidone both increase QTc interval. Modify Therapy/Monitor Closely. risperidone and amitriptyline both increase sedation. Use Caution/Monitor.ritonavirMonitor Closely (2)ritonavir 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.rivastigmineMonitor Closely (1)rivastigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.rizatriptanMonitor Closely (1)rizatriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.rocuroniumMonitor Closely (1)rocuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.rolapitantMonitor Closely (1)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.romidepsinMonitor Closely (1)amitriptyline and romidepsin both increase QTc interval. Modify Therapy/Monitor Closely.rosiglitazoneMinor (1)amitriptyline increases effects of rosiglitazone by pharmacodynamic synergism. Minor/Significance Unknown.rufinamideMinor (1)rufinamide will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.safinamideContraindicated (1)amitriptyline, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.sageMinor (1)amitriptyline and sage both increase sedation. Minor/Significance Unknown.salmeterolMonitor Closely (1)amitriptyline increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, 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)amitriptyline and SAMe both increase serotonin levels. Modify Therapy/Monitor Closely.sarecyclineMonitor Closely (1)sarecycline will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.saxagliptinMinor (1)amitriptyline increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.scopolamineMonitor Closely (1)scopolamine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.scullcapMonitor Closely (1)amitriptyline and scullcap both increase sedation. Use Caution/Monitor.secobarbitalMonitor Closely (2)secobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. secobarbital and amitriptyline both increase sedation. Use Caution/Monitor.Minor (1)secobarbital, 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.selegilineContraindicated (1)selegiline and amitriptyline both increase serotonin levels. Contraindicated. Concurrent use or use within 14 days of selegiline treatment is contraindicatedselegiline transdermalSerious - Use Alternative (1)selegiline transdermal and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.selinexorSerious - Use Alternative (1)selinexor, amitriptyline. 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 amitriptyline by QTc interval. Use Caution/Monitor.serdexmethylphenidate/dexmethylphenidateSerious - Use Alternative (1)amitriptyline, 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 amitriptyline by decreasing metabolism. Minor/Significance Unknown.sertralineMonitor Closely (1)sertraline and amitriptyline both increase QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)sertraline and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.sevofluraneMonitor Closely (2)sevoflurane and amitriptyline both increase QTc interval. Use Caution/Monitor. sevoflurane and amitriptyline both increase sedation. Use Caution/Monitor.Minor (1)sevoflurane, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.shepherd's purseMonitor Closely (1)amitriptyline and shepherd's purse both increase sedation. Use Caution/Monitor.simvastatinMonitor Closely (1)simvastatin will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.sirolimusMonitor Closely (1)sirolimus will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.sitagliptinMinor (1)amitriptyline increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.sodium oxybateSerious - Use Alternative (1)amitriptyline, 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 amitriptyline 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)amitriptyline, 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 amitriptyline 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 amitriptyline both increase QTc interval. Use Caution/Monitor. solifenacin and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.sorafenibMonitor Closely (1)sorafenib and amitriptyline both increase QTc interval. Use Caution/Monitor.sotalolContraindicated (1)amitriptyline and sotalol both increase QTc interval. Contraindicated.St John's WortMonitor Closely (2)St John's Wort will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. St John's Wort will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)amitriptyline and St John's Wort both increase serotonin levels. Avoid or Use Alternate Drug.stiripentolMonitor Closely (1)stiripentol, amitriptyline. 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 amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.sufentanilMonitor Closely (1)sufentanil and amitriptyline both increase sedation. Use Caution/Monitor.sufentanil SLMonitor Closely (1)sufentanil SL, amitriptyline. 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 syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.sulfamethoxazoleMonitor Closely (1)amitriptyline and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)sulfamethoxazole decreases levels of amitriptyline by unspecified interaction mechanism. Minor/Significance Unknown.sumatriptanMonitor Closely (1)sumatriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.sumatriptan intranasalMonitor Closely (1)sumatriptan intranasal and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.suvorexantMonitor Closely (1)suvorexant and amitriptyline both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants