perphenazine and risperidone both increase antidopaminergic effects, including extrapyramidal symptoms and neuroleptic malignant syndrome. Use Caution/Monitor.Minor (1)perphenazine will increase the level or effect of risperidone by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.ritonavirMonitor Closely (2)ritonavir will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. ritonavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)ritonavir will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.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 (2)rizatriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely. rizatriptan, 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).rocuroniumMonitor Closely (4)rocuronium 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. rocuronium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. perphenazine increases effects of rocuronium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.rolapitantMonitor Closely (2)rolapitant 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.romidepsinMonitor Closely (2)perphenazine and romidepsin both increase QTc interval. Modify Therapy/Monitor Closely. amitriptyline and romidepsin both increase QTc interval. Modify Therapy/Monitor Closely.ropiniroleSerious - Use Alternative (1)perphenazine decreases effects of ropinirole by pharmacodynamic antagonism. Contraindicated.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.Serious - Use Alternative (1)perphenazine decreases effects of safinamide by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Dopamine antagonists may decrease safinamide effects and exacerbate Parkinson disease symptoms.sageMinor (2)perphenazine and sage both increase sedation. Minor/Significance Unknown. amitriptyline and sage both increase sedation. Minor/Significance Unknown.salmeterolMonitor Closely (2)perphenazine 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.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.saquinavirSerious - Use Alternative (1)saquinavir, perphenazine. Either increases toxicity of the other by QTc interval. Avoid or Use Alternate Drug. Increased risk of PR or QT prolongation and cardiac arrhythmias.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 (4)scopolamine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor. scopolamine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. perphenazine increases effects of scopolamine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia. scopolamine and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.scullcapMonitor Closely (2)perphenazine and scullcap both increase sedation. Use Caution/Monitor. amitriptyline and scullcap both increase sedation. Use Caution/Monitor.secobarbitalMonitor Closely (3)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. secobarbital and perphenazine 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 contraindicatedMonitor Closely (1)selegiline, 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).selegiline transdermalSerious - Use Alternative (1)selegiline transdermal and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.selinexorSerious - Use Alternative (2)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. selinexor, perphenazine. 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 (2)selpercatinib increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor. selpercatinib increases toxicity of perphenazine by QTc interval. Use Caution/Monitor.serdexmethylphenidate/dexmethylphenidateMonitor Closely (1)perphenazine, serdexmethylphenidate/dexmethylphenidate. 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, 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 (2)sertraline and perphenazine both increase QTc interval. Use Caution/Monitor. 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.Minor (1)sertraline will increase the level or effect of perphenazine by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.sevofluraneMonitor Closely (4)sevoflurane and amitriptyline both increase sedation. Use Caution/Monitor. sevoflurane and perphenazine both increase sedation. Use Caution/Monitor. sevoflurane and amitriptyline both increase QTc interval. Use Caution/Monitor. sevoflurane and perphenazine both increase QTc interval. Use Caution/Monitor.Minor (1)sevoflurane, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.shepherd's purseMonitor Closely (2)perphenazine and shepherd's purse both increase sedation. Use Caution/Monitor. 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.siponimodMonitor Closely (1)siponimod and perphenazine both increase QTc interval. 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.smokingMonitor Closely (1)smoking decreases levels of perphenazine by increasing metabolism. Use Caution/Monitor. Interaction mainly seen w/chlorpromazine & thioridazine, but may occur w/other phenothiazines.sodium oxybateSerious - Use Alternative (2)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. perphenazine, 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 (2)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/?magnesium sulfate/potassium chloride increases effects of perphenazine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.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 (2)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. sodium sulfate/potassium sulfate/magnesium sulfate increases effects of perphenazine by unknown mechanism. Use Caution/Monitor. Closely monitor for evidence of enhanced CNS depression when using higher dose of magnesium sulfate together with a CNS depressant.solifenacinMonitor Closely (6)solifenacin and perphenazine both increase QTc interval. Use Caution/Monitor. solifenacin and amitriptyline both increase QTc interval. Use Caution/Monitor. solifenacin decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. solifenacin and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. solifenacin decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor. perphenazine increases effects of solifenacin by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.sorafenibMonitor Closely (2)sorafenib and amitriptyline both increase QTc interval. Use Caution/Monitor. sorafenib and perphenazine both increase QTc interval. Use Caution/Monitor.sotalolContraindicated (2)perphenazine and sotalol both increase QTc interval. Contraindicated. 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 (2)stiripentol, perphenazine. 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. 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 (2)sufentanil and amitriptyline both increase sedation. Use Caution/Monitor. sufentanil and perphenazine 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.Serious - Use Alternative (1)sufentanil SL, perphenazine. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. 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.sulfamethoxazoleMonitor Closely (2)amitriptyline and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely. perphenazine 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 (2)sumatriptan, 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). sumatriptan and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.sumatriptan intranasalMonitor Closely (2)sumatriptan intranasal, 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). sumatriptan intranasal and amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.sunitinibMonitor Closely (1)sunitinib and perphenazine both increase QTc interval. Use Caution/Monitor.suvorexantMonitor Closely (1)suvorexant and amitriptyline both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be