Use Caution/Monitor. Slight and transient QT-prolongation observed with ezogabine, particularly when dose titrated to 1200 mg/day. QT interval should be monitored when ezogabine is prescribed with agents known to increase QT interval.fedratinibMonitor Closely (1)fedratinib will increase the level or effect of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.fenfluramineMonitor Closely (3)fenfluramine, protriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration with drugs that increase serotoninergic effects may increase the risk of serotonin syndrome. protriptyline and fenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely. protriptyline increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, fenfluramine. 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.fesoterodineMonitor Closely (1)fesoterodine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.fexinidazoleSerious - Use Alternative (1)fexinidazole and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.fingolimodMonitor Closely (1)fingolimod and protriptyline both increase QTc interval. Use Caution/Monitor.flavoxateMonitor Closely (1)flavoxate and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.flecainideMonitor Closely (1)protriptyline and flecainide both increase QTc interval. Modify Therapy/Monitor Closely.fluconazoleSerious - Use Alternative (1)protriptyline and fluconazole both increase QTc interval. Avoid or Use Alternate Drug.fluoxetineMonitor Closely (1)protriptyline and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)fluoxetine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.fluphenazineMonitor Closely (1)fluphenazine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fluphenazine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)protriptyline, fluphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects. protriptyline, fluphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.flurazepamMonitor Closely (1)flurazepam and protriptyline both increase sedation. Use Caution/Monitor.fluvoxamineMonitor Closely (1)fluvoxamine and protriptyline both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)fluvoxamine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.formoterolMonitor Closely (1)protriptyline increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (2)protriptyline and formoterol both increase QTc interval. Avoid or Use Alternate Drug. protriptyline, formoterol. 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.fosamprenavirSerious - Use Alternative (1)fosamprenavir increases levels of protriptyline by decreasing metabolism. Avoid or Use Alternate Drug.foscarnetMonitor Closely (1)protriptyline and foscarnet both increase QTc interval. Modify Therapy/Monitor Closely.frovatriptanMonitor Closely (1)frovatriptan and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.gabapentinMonitor Closely (1)gabapentin, 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.gabapentin enacarbilMonitor Closely (1)gabapentin enacarbil, 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.galantamineMonitor Closely (1)galantamine increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.ganaxoloneMonitor Closely (1)protriptyline and ganaxolone both increase sedation. Use Caution/Monitor.gemifloxacinMonitor Closely (1)gemifloxacin and protriptyline both increase QTc interval. Use Caution/Monitor.gilteritinibMonitor Closely (1)gilteritinib and protriptyline both increase QTc interval. Use Caution/Monitor.givosiranSerious - Use Alternative (1)givosiran will increase the level or effect of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.glimepirideMinor (1)protriptyline increases effects of glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.glipizideMinor (1)protriptyline increases effects of glipizide by pharmacodynamic synergism. Minor/Significance Unknown.glyburideMinor (1)protriptyline increases effects of glyburide by pharmacodynamic synergism. Minor/Significance Unknown.glycopyrrolateMonitor Closely (2)glycopyrrolate and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. protriptyline increases levels of glycopyrrolate by unknown mechanism. Use Caution/Monitor.glycopyrrolate inhaledMonitor Closely (2)glycopyrrolate inhaled and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. protriptyline increases levels of glycopyrrolate inhaled by unknown mechanism. Use Caution/Monitor.glycopyrronium tosylate topicalMonitor Closely (1)glycopyrronium tosylate topical, protriptyline. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of glycopyrronium tosylate topical with other anticholinergic medications may result in additive anticholinergic adverse effects.granisetronMonitor Closely (1)granisetron and protriptyline both increase QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)granisetron, protriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.guanfacineSerious - Use Alternative (1)protriptyline decreases effects of guanfacine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.haloperidolMonitor Closely (1)haloperidol and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline and haloperidol both increase QTc interval. Avoid or Use Alternate Drug.henbaneMonitor Closely (1)henbane and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.homatropineMonitor Closely (1)homatropine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.huperzine AMonitor Closely (1)huperzine A increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.hydrocodoneMonitor Closely (1)hydrocodone, 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 syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.hydromorphoneMonitor Closely (1)hydromorphone and protriptyline both increase sedation. Use Caution/Monitor.hydroxychloroquine sulfateSerious - Use Alternative (1)hydroxychloroquine sulfate and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.hydroxyprogesterone caproate (DSC)Minor (1)hydroxyprogesterone caproate (DSC), protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.hydroxyzineMonitor Closely (2)hydroxyzine and protriptyline both increase sedation. Use Caution/Monitor. hydroxyzine and protriptyline both increase QTc interval. Use Caution/Monitor.hyoscyamineMonitor Closely (1)hyoscyamine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.hyoscyamine sprayMonitor Closely (1)hyoscyamine spray and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.ibutilideContraindicated (1)protriptyline and ibutilide both increase QTc interval. Contraindicated.iloperidoneMonitor Closely (2)protriptyline and iloperidone both increase QTc interval. Modify Therapy/Monitor Closely. iloperidone and protriptyline both increase sedation. Use Caution/Monitor.imipramineMonitor Closely (2)imipramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. imipramine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)imipramine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. imipramine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.indacaterol, inhaledMonitor Closely (1)indacaterol, inhaled, protriptyline. QTc interval. Use Caution/Monitor. Indacaterol should be administered with extreme caution to patients treated with TCAs. Drugs that are known to prolong the QTc interval may have an increased the risk of ventricular arrhythmias.indapamideContraindicated (1)protriptyline and indapamide both increase QTc interval. Contraindicated.insulin aspartMinor (1)protriptyline increases effects of insulin aspart by pharmacodynamic synergism. Minor/Significance Unknown.insulin detemirMinor (1)protriptyline increases effects of insulin detemir by pharmacodynamic synergism. Minor/Significance Unknown.insulin glargineMinor (1)protriptyline increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.insulin glulisineMinor (1)protriptyline increases effects of insulin glulisine by pharmacodynamic synergism. Minor/Significance Unknown.insulin lisproMinor (1)protriptyline increases effects of insulin lispro by pharmacodynamic synergism. Minor/Significance Unknown.insulin NPHMinor (1)protriptyline increases effects of insulin NPH by pharmacodynamic synergism. Minor/Significance Unknown.insulin regular humanMinor (1)protriptyline increases effects of insulin regular human by pharmacodynamic synergism. Minor/Significance Unknown.iobenguane I 123Contraindicated (1)protriptyline 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)protriptyline 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 (1)ipratropium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.isocarboxazidContraindicated (1)isocarboxazid and protriptyline both increase serotonin levels. Contraindicated.isofluraneMonitor Closely (1)isoflurane and protriptyline both increase QTc interval. Use Caution/Monitor.isoniazidMonitor Closely (1)protriptyline and isoniazid both increase serotonin levels. Modify Therapy/Monitor Closely.isoproterenolMonitor Closely (1)protriptyline increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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, protriptyline. Mechanism: unknown. Minor/Significance Unknown. Risk of cardiac arrhythmias.itraconazoleSerious - Use Alternative (1)protriptyline and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.ivosidenibSerious - Use Alternative (1)ivosidenib and protriptyline 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 (1)ketamine and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)ketamine, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.ketoconazoleSerious - Use Alternative (1)protriptyline and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.ketotifen, ophthalmicMonitor Closely (1)protriptyline and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.L-tryptophanMonitor Closely (1)protriptyline and L-tryptophan both increase serotonin levels. Modify Therapy/Monitor Closely.lapatinibMonitor Closely (1)protriptyline and lapatinib both increase QTc interval. Modify Therapy/Monitor Closely.lasmiditanMonitor Closely (2)lasmiditan, protriptyline. 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. protriptyline increases effects of lasmiditan by serotonin levels. Use Caution/Monitor. Coadministration may increase risk of serotonin syndrome.lemborexantMonitor Closely (1)lemborexant, protriptyline. 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.levalbuterolMonitor Closely (1)protriptyline increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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.levofloxacinMonitor Closely (1)protriptyline and levofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.levoketoconazoleSerious - Use Alternative (1)protriptyline and levoketoconazole both increase QTc interval. Avoid or Use Alternate Drug.levomilnacipranSerious - Use Alternative (1)levomilnacipran and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.levorphanolMonitor Closely (1)levorphanol and protriptyline both increase sedation. Use Caution/Monitor.levothyroxineMonitor Closely (1)levothyroxine increases effects of protriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.linezolidSerious - Use Alternative (1)linezolid and protriptyline 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 protriptyline 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 protriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.lisdexamfetamineMonitor Closely (2)protriptyline, 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). protriptyline increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, 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.lithiumMonitor Closely (2)lithium and protriptyline both increase QTc interval. Use Caution/Monitor. protriptyline and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)lithium, protriptyline. Other (see comment). Minor/Significance Unknown. Comment: Risk of neurotoxicity in geriatric pts. Multiple mechanisms involved.lofepramineMonitor Closely (2)lofepramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. lofepramine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)lofepramine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. lofepramine and protriptyline