Caution/Monitor.anticholinergic/sedative combosanticholinergic/sedative combos and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.apomorphineprotriptyline and apomorphine both increase sedation. Use Caution/Monitor.arformoterolprotriptyline increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.arformoterol and protriptyline both increase QTc interval. Use Caution/Monitor.aripiprazolearipiprazole and protriptyline both increase sedation. Use Caution/Monitor.armodafinilprotriptyline increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.asenapineasenapine and protriptyline both increase QTc interval. Use Caution/Monitor.asenapine and protriptyline both increase sedation. Use Caution/Monitor.asenapine transdermalasenapine transdermal and protriptyline both increase QTc interval. Use Caution/Monitor.asenapine transdermal and protriptyline both increase sedation. Use Caution/Monitor.atazanaviratazanavir increases levels of protriptyline by unspecified interaction mechanism. Use Caution/Monitor.atomoxetineatomoxetine and protriptyline both increase QTc interval. Use Caution/Monitor.atracuriumatracurium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.atropineatropine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.atropine IV/IMatropine IV/IM and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.avapritinibavapritinib and protriptyline both increase sedation. Use Caution/Monitor.azelastineazelastine and protriptyline both increase sedation. Use Caution/Monitor.azithromycinprotriptyline and azithromycin both increase QTc interval. Use Caution/Monitor.baclofenbaclofen and protriptyline both increase sedation. Use Caution/Monitor.bedaquilineprotriptyline and bedaquiline both increase QTc interval. Modify Therapy/Monitor Closely. ECG should be monitored closelybelladonna alkaloidsbelladonna alkaloids and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.belladonna and opiumbelladonna and opium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.belladonna and opium and protriptyline both increase sedation. Use Caution/Monitor.benperidolbenperidol and protriptyline both increase sedation. Use Caution/Monitor.benzhydrocodone/acetaminophenbenzhydrocodone/acetaminophen, 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.benzphetamineprotriptyline increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.benztropinebenztropine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.bethanecholbethanechol increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.brexpiprazolebrexpiprazole and protriptyline both increase sedation. Use Caution/Monitor.brimonidinebrimonidine and protriptyline both increase sedation. Use Caution/Monitor.brivaracetambrivaracetam and protriptyline both increase sedation. Use Caution/Monitor.brompheniraminebrompheniramine and protriptyline both increase sedation. Use Caution/Monitor.buprenorphinebuprenorphine and protriptyline both increase sedation. Use Caution/Monitor.buprenorphine buccalbuprenorphine buccal and protriptyline both increase sedation. Use Caution/Monitor.buprenorphine subdermal implantprotriptyline, buprenorphine subdermal implant. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.buprenorphine, long-acting injectionprotriptyline, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.bupropionprotriptyline increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.bupropion will increase the level or effect of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.butabarbitalbutabarbital and protriptyline both increase sedation. Use Caution/Monitor.butalbitalbutalbital and protriptyline both increase sedation. Use Caution/Monitor.butorphanolbutorphanol and protriptyline both increase sedation. Use Caution/Monitor.caffeineprotriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.carbacholcarbachol increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.carbinoxaminecarbinoxamine and protriptyline both increase sedation. Use Caution/Monitor.carisoprodolcarisoprodol and protriptyline both increase sedation. Use Caution/Monitor.cenobamatecenobamate, protriptyline. Either increases effects of the other by sedation. Use Caution/Monitor.ceritinibceritinib and protriptyline both increase QTc interval. Use Caution/Monitor.cevimelinecevimeline increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.chloral hydratechloral hydrate and protriptyline both increase sedation. Use Caution/Monitor.chlordiazepoxidechlordiazepoxide and protriptyline both increase sedation. Use Caution/Monitor.chlorpheniraminechlorpheniramine and protriptyline both increase sedation. Use Caution/Monitor.chlorpromazinechlorpromazine and protriptyline both increase sedation. Use Caution/Monitor.chlorzoxazonechlorzoxazone and protriptyline both increase sedation. Use Caution/Monitor.cinnarizinecinnarizine and protriptyline both increase sedation. Use Caution/Monitor.cisatracuriumcisatracurium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.clemastineclemastine and protriptyline both increase sedation. Use Caution/Monitor.clobazamclobazam will increase the level or effect of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly. protriptyline, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).clomipramineclomipramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.clomipramine and protriptyline both increase sedation. Use Caution/Monitor.clonazepamclonazepam and protriptyline both increase sedation. Use Caution/Monitor.clorazepateclorazepate and protriptyline both increase sedation. Use Caution/Monitor.clozapineclozapine and protriptyline both increase sedation. Use Caution/Monitor.clozapine and protriptyline both increase QTc interval. Use Caution/Monitor.cobicistatcobicistat will increase the level or effect of protriptyline by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat. cocaine topicalprotriptyline and cocaine topical both increase serotonin levels. Modify Therapy/Monitor Closely.codeinecodeine and protriptyline both increase sedation. Use Caution/Monitor.crizotinibcrizotinib and protriptyline both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.cyclizinecyclizine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.cyclizine and protriptyline both increase sedation. Use Caution/Monitor.cyclobenzaprinecyclobenzaprine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.cyclobenzaprine and protriptyline both increase sedation. Use Caution/Monitor.cyproheptadinecyproheptadine and protriptyline both increase sedation. Use Caution/Monitor.dantrolenedantrolene and protriptyline both increase sedation. Use Caution/Monitor.daridorexantprotriptyline and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment. darifenacindarifenacin and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.dasatinibprotriptyline and dasatinib both increase QTc interval. Modify Therapy/Monitor Closely.debrisoquineprotriptyline decreases effects of debrisoquine by Other (see comment). Use Caution/Monitor. Comment: Inhibition of uptake by adrenergic neurons.degarelixdegarelix and protriptyline both increase QTc interval. Use Caution/Monitor.desfluranedesflurane and protriptyline both increase sedation. Use Caution/Monitor.desflurane and protriptyline both increase QTc interval. Use Caution/Monitor.desipraminedesipramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.desipramine and protriptyline both increase sedation. Use Caution/Monitor.deutetrabenazineprotriptyline and deutetrabenazine both increase sedation. Use Caution/Monitor.deutetrabenazine and protriptyline both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).dexchlorpheniraminedexchlorpheniramine and protriptyline both increase sedation. Use Caution/Monitor.dexfenfluramineprotriptyline increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.protriptyline and dexfenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.dexmedetomidinedexmedetomidine and protriptyline both increase sedation. Use Caution/Monitor.dexmethylphenidateprotriptyline increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.dextroamphetamineprotriptyline increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.protriptyline and dextroamphetamine both increase serotonin levels. Modify Therapy/Monitor Closely.protriptyline increases effects of dextroamphetamine by unknown mechanism. Use Caution/Monitor.dextroamphetamine transdermalprotriptyline will increase the level or effect of dextroamphetamine transdermal by pharmacodynamic synergism. Modify Therapy/Monitor Closely. May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in dextroamphetamine levels in brain; May be potentiate cardiovascular effects. Monitor frequently and adjust or use an alternant based on clinical response.dextromoramidedextromoramide and protriptyline both increase sedation. Use Caution/Monitor.diamorphinediamorphine and protriptyline both increase sedation. Use Caution/Monitor.diazepamdiazepam and protriptyline both increase sedation. Use Caution/Monitor.diazepam intranasaldiazepam intranasal, protriptyline. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.dicyclominedicyclomine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.diethylpropionprotriptyline increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.difelikefalindifelikefalin and protriptyline both increase sedation. Use Caution/Monitor.difenoxin hcldifenoxin hcl and protriptyline both increase sedation. Use Caution/Monitor.dihydroergotamineprotriptyline and dihydroergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.dihydroergotamine intranasalprotriptyline and dihydroergotamine intranasal both increase serotonin levels. Modify Therapy/Monitor Closely.dimenhydrinatedimenhydrinate and protriptyline both increase sedation. Use Caution/Monitor.diphenhydraminediphenhydramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.diphenhydramine and protriptyline both increase sedation. Use Caution/Monitor.diphenoxylate hcldiphenoxylate hcl and protriptyline both increase sedation. Use Caution/Monitor.dipipanonedipipanone and protriptyline both increase sedation. Use Caution/Monitor.dobutamineprotriptyline increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.dofetilidedofetilide increases toxicity of protriptyline by QTc interval. Use Caution/Monitor.dolasetronprotriptyline and dolasetron both increase QTc interval. Modify Therapy/Monitor Closely.donepezildonepezil increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.donepezil and protriptyline both increase QTc interval. Use Caution/Monitor.dopamineprotriptyline increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.dopexamineprotriptyline increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.doxepindoxepin and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.doxepin and protriptyline both increase sedation. Use Caution/Monitor.doxylaminedoxylamine and protriptyline both increase sedation. Use Caution/Monitor.droperidoldroperidol and protriptyline both increase sedation. Use Caution/Monitor.echothiophate iodideechothiophate iodide increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.efavirenzefavirenz and protriptyline both increase QTc interval. Use Caution/Monitor.eletriptaneletriptan and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.eliglustateliglustat increases levels of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the concomitant drug and titrate to clinical effect.eliglustat and protriptyline both increase QTc interval. Use Caution/Monitor.elvitegravir/cobicistat/emtricitabine/tenofovir DFelvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.entrectinibentrectinib and protriptyline both increase QTc interval. Use Caution/Monitor.ephedrineprotriptyline increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.protriptyline increases effects of ephedrine by unknown mechanism. Use Caution/Monitor.epinephrineprotriptyline increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.protriptyline increases effects of epinephrine by unknown mechanism. Use Caution/Monitor.epinephrine inhaledprotriptyline and epinephrine inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Use Caution/Monitor. Tricyclic antidepressants may potentiate epinephrine effect on cardiovascular system.epinephrine racemicprotriptyline increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.protriptyline increases effects of epinephrine racemic by unknown mechanism. Use Caution/Monitor.ergotamineprotriptyline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.eribulineribulin and protriptyline both increase QTc interval. Use Caution/Monitor.escitalopramescitalopram increases toxicity of protriptyline by QTc interval. Use Caution/Monitor.esketamine intranasalesketamine intranasal, protriptyline. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.estazolamestazolam and protriptyline both increase sedation. Use Caution/Monitor.ethanolprotriptyline and ethanol both increase sedation. Use Caution/Monitor.etomidateetomidate and protriptyline both increase sedation. Use Caution/Monitor.ezogabineezogabine, protriptyline. Either increases toxicity of the other by QTc interval. 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.fedratinibfedratinib 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.fenfluramineprotriptyline increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.protriptyline and fenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.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.fesoterodinefesoterodine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.fingolimodfingolimod and protriptyline both increase QTc interval. Use Caution/Monitor.flavoxateflavoxate and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.flecainideprotriptyline and flecainide both increase QTc interval. Modify Therapy/Monitor Closely.fluoxetineprotriptyline and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely.fluphenazinefluphenazine and protriptyline both increase sedation. Use Caution/Monitor.flurazepamflurazepam and protriptyline both increase sedation. Use Caution/Monitor.fluvoxaminefluvoxamine and protriptyline both increase QTc interval. Modify Therapy/Monitor Closely.formoterolprotriptyline increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.foscarnetprotriptyline and foscarnet both increase QTc interval. Modify Therapy/Monitor Closely.frovatriptanfrovatriptan and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.gabapentingabapentin, 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 enacarbilgabapentin 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.galantaminegalantamine increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.ganaxoloneprotriptyline and ganaxolone both increase sedation. Use Caution/Monitor.gemifloxacingemifloxacin and protriptyline both increase QTc interval. Use Caution/Monitor.gilteritinibgilteritinib and protriptyline both increase QTc interval. Use