glargineMinor (1)amitriptyline increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.insulin glulisineMinor (1)amitriptyline increases effects of insulin glulisine by pharmacodynamic synergism. Minor/Significance Unknown.insulin inhaledMonitor Closely (1)perphenazine decreases effects of insulin inhaled by Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase blood glucose concentrations.insulin lisproMinor (1)amitriptyline increases effects of insulin lispro by pharmacodynamic synergism. Minor/Significance Unknown.insulin NPHMinor (1)amitriptyline increases effects of insulin NPH by pharmacodynamic synergism. Minor/Significance Unknown.insulin regular humanMinor (1)amitriptyline increases effects of insulin regular human by pharmacodynamic synergism. Minor/Significance Unknown.iobenguane I 123Contraindicated (1)amitriptyline decreases effects of iobenguane I 123 by pharmacodynamic antagonism. Contraindicated. If clinically appropriate, discontinue drugs that decrease uptake of NE for at least 5 half-lives; may cause false-negative imaging results.iobenguane I 131Serious - Use Alternative (1)amitriptyline will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.ipratropiumMonitor Closely (4)ipratropium and amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. Due to the poor systemic absorption of ipratropium, interaction unlikely at regularly recommended dosages. ipratropium decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor. ipratropium decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor. perphenazine increases effects of ipratropium by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.isocarboxazidContraindicated (1)isocarboxazid and amitriptyline both increase serotonin levels. Contraindicated.Serious - Use Alternative (1)isocarboxazid, perphenazine. Other (see comment). Contraindicated. Comment: Concurrent use may prolong or intensify the hypotensive, anticholinergic, or sedative effects of isocarboxazid or perphenazine.isofluraneMonitor Closely (2)isoflurane and amitriptyline both increase QTc interval. Use Caution/Monitor. isoflurane and perphenazine both increase QTc interval. Use Caution/Monitor.isoniazidMonitor Closely (2)amitriptyline and isoniazid both increase serotonin levels. Modify Therapy/Monitor Closely. isoniazid will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.Minor (1)isoniazid will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.isoproterenolMonitor Closely (3)perphenazine increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. amitriptyline increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. perphenazine, isoproterenol. 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, isoproterenol. 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)isoproterenol, amitriptyline. Mechanism: unknown. Minor/Significance Unknown. Risk of cardiac arrhythmias.istradefyllineMonitor Closely (1)istradefylline will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.itraconazoleMonitor Closely (2)itraconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. itraconazole and amitriptyline both increase QTc interval. Use Caution/Monitor.Minor (1)itraconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.Serious - Use Alternative (1)perphenazine and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.ivacaftorMonitor Closely (1)ivacaftor increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.ivosidenibSerious - Use Alternative (2)ivosidenib and perphenazine both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of QTc prolonging drugs with ivosidenib or replace with alternate therapies. If coadministration of a QTc prolonging drug is unavoidable, monitor for increased risk of QTc interval prolongation. ivosidenib and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of QTc prolonging drugs with ivosidenib or replace with alternate therapies. If coadministration of a QTc prolonging drug is unavoidable, monitor for increased risk of QTc interval prolongation.ketamineMonitor Closely (2)ketamine and amitriptyline both increase sedation. Use Caution/Monitor. ketamine and perphenazine both increase sedation. Use Caution/Monitor.Minor (1)ketamine, amitriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.ketoconazoleMonitor Closely (2)ketoconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. ketoconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (2)perphenazine and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.ketotifen, ophthalmicMonitor Closely (2)perphenazine and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor. amitriptyline and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.L-tryptophanMonitor Closely (1)amitriptyline and L-tryptophan both increase serotonin levels. Modify Therapy/Monitor Closely.lapatinibMonitor Closely (2)amitriptyline and lapatinib both increase QTc interval. Modify Therapy/Monitor Closely. perphenazine and lapatinib both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)lapatinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.lasmiditanMonitor Closely (3)lasmiditan, amitriptyline. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions. lasmiditan, perphenazine. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions. amitriptyline increases effects of lasmiditan by serotonin levels. Use Caution/Monitor. Coadministration may increase risk of serotonin syndrome.Serious - Use Alternative (1)lasmiditan increases effects of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.lefamulinSerious - Use Alternative (1)lefamulin and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.lemborexantMonitor Closely (2)lemborexant, perphenazine. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects. lemborexant, amitriptyline. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.letermovirMonitor Closely (1)letermovir increases levels of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.levalbuterolMonitor Closely (2)perphenazine increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. amitriptyline increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, levalbuterol. 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.levodopaSerious - Use Alternative (1)perphenazine decreases effects of levodopa by pharmacodynamic antagonism. Avoid or Use Alternate Drug.levodopa inhaledSerious - Use Alternative (1)perphenazine decreases effects of levodopa inhaled by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Phenothiazine/1st generation antipsychotics inhibit dopamine D2 receptors in varying degrees.levofloxacinMonitor Closely (2)amitriptyline and levofloxacin both increase QTc interval. Modify Therapy/Monitor Closely. perphenazine and levofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.levoketoconazoleMonitor Closely (2)levoketoconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. levoketoconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (2)perphenazine and levoketoconazole both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and levoketoconazole both increase QTc interval. Avoid or Use Alternate Drug.levomilnacipranMonitor Closely (1)levomilnacipran, 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).Serious - Use Alternative (1)levomilnacipran and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.levorphanolMonitor Closely (2)levorphanol and amitriptyline both increase sedation. Use Caution/Monitor. levorphanol and perphenazine both increase sedation. Use Caution/Monitor.levothyroxineMonitor Closely (1)levothyroxine increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.linezolidMonitor Closely (1)linezolid, 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).Serious - Use Alternative (1)linezolid and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.liothyronineMonitor Closely (1)liothyronine increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.liotrixMonitor Closely (1)liotrix increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.liraglutideMonitor Closely (1)perphenazine, liraglutide. Other (see comment). Use Caution/Monitor. Comment: Phenothiazines may increase or decrease glucose levels, monitor therapy closely when these agents are concurrently administered.lisdexamfetamineMonitor Closely (4)amitriptyline increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. amitriptyline, lisdexamfetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue along with concomitant serotonergic drug(s). perphenazine, lisdexamfetamine. 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. perphenazine increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, lisdexamfetamine. 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.lisinoprilMinor (1)perphenazine increases effects of lisinopril by unspecified interaction mechanism. Minor/Significance Unknown.lisurideSerious - Use Alternative (1)perphenazine decreases effects of lisuride by pharmacodynamic antagonism. Contraindicated.lithiumMonitor Closely (5)lithium and amitriptyline both increase QTc interval. Use Caution/Monitor. lithium and perphenazine both increase QTc interval. Use Caution/Monitor. lithium, 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). amitriptyline and lithium both increase serotonin levels. Modify Therapy/Monitor Closely. lithium, perphenazine. Other (see comment). Use Caution/Monitor. Comment: Risk of neurotoxicity. Multiple mechanisms involved.Minor (1)lithium, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Risk of neurotoxicity in geriatric pts. Multiple mechanisms involved.lofepramineMonitor Closely (4)perphenazine and lofepramine both increase sedation. Use Caution/Monitor. amitriptyline and lofepramine both increase sedation. Use Caution/Monitor. amitriptyline and lofepramine both decrease cholinergic effects/transmission. Use Caution/Monitor. perphenazine will increase the level or effect of lofepramine by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (3)amitriptyline and lofepramine both increase QTc interval. Avoid or Use Alternate Drug. amitriptyline and lofepramine both increase serotonin levels. Avoid or Use Alternate Drug. perphenazine and lofepramine both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)lofepramine, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects. lofepramine, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.lofexidineMonitor Closely (3)perphenazine and lofexidine both increase sedation. Use Caution/Monitor. amitriptyline decreases effects of lofexidine by unspecified interaction mechanism. Use Caution/Monitor. amitriptyline and lofexidine both increase sedation. Use Caution/Monitor.loprazolamMonitor Closely (2)loprazolam and amitriptyline both increase sedation. Use Caution/Monitor. loprazolam and perphenazine both increase sedation. Use Caution/Monitor.loratadineMonitor Closely (1)loratadine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)perphenazine will increase the level or effect of loratadine by affecting