of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.abobotulinumtoxinAMonitor Closely (1)abobotulinumtoxinA increases effects of protriptyline by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects. .acarboseMinor (1)protriptyline increases effects of acarbose by pharmacodynamic synergism. Minor/Significance Unknown.aclidiniumMonitor Closely (1)aclidinium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.acrivastineMonitor Closely (1)acrivastine and protriptyline both increase sedation. Use Caution/Monitor.adagrasibSerious - Use Alternative (1)adagrasib, protriptyline. Either increases effects of the other by QTc interval. Avoid or Use Alternate Drug. Each drug prolongs the QTc interval, which may increased the risk of Torsade de pointes, other serious arryhthmias, and sudden death. If coadministration unavoidable, more frequent monitoring is recommended for such patients.albuterolMonitor Closely (2)albuterol and protriptyline both increase QTc interval. Use Caution/Monitor. protriptyline increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, albuterol. 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.alfentanilMonitor Closely (1)alfentanil and protriptyline both increase sedation. Use Caution/Monitor.alfuzosinMonitor Closely (2)protriptyline and alfuzosin both increase QTc interval. Use Caution/Monitor. alfuzosin and protriptyline both increase QTc interval. Use Caution/Monitor.almotriptanMonitor Closely (1)almotriptan and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.alprazolamMonitor Closely (1)alprazolam and protriptyline both increase sedation. Use Caution/Monitor.amifampridineMonitor Closely (1)protriptyline increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.amiodaroneSerious - Use Alternative (1)protriptyline and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.amisulprideMonitor Closely (1)protriptyline and amisulpride both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended if coadministered.amitriptylineMonitor 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.amobarbitalMonitor Closely (1)amobarbital and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)amobarbital, protriptyline. 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.amoxapineMonitor Closely (2)amoxapine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. amoxapine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)amoxapine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. amoxapine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.anagrelideMonitor Closely (1)anagrelide and protriptyline both increase QTc interval. Use Caution/Monitor.anticholinergic/sedative combosMonitor Closely (1)anticholinergic/sedative combos and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.apomorphineMonitor Closely (1)protriptyline and apomorphine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)apomorphine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.arformoterolMonitor Closely (2)arformoterol and protriptyline both increase QTc interval. Use Caution/Monitor. protriptyline increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, arformoterol. 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.aripiprazoleMonitor Closely (1)aripiprazole and protriptyline both increase sedation. Use Caution/Monitor.armodafinilMonitor Closely (1)protriptyline increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.arsenic trioxideSerious - Use Alternative (1)protriptyline and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.artemetherSerious - Use Alternative (1)artemether and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.artemether/lumefantrineSerious - Use Alternative (1)protriptyline and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.asenapineMonitor Closely (2)asenapine and protriptyline both increase QTc interval. Use Caution/Monitor. asenapine and protriptyline both increase sedation. Use Caution/Monitor.asenapine transdermalMonitor Closely (2)asenapine transdermal and protriptyline both increase QTc interval. Use Caution/Monitor. asenapine transdermal and protriptyline both increase sedation. Use Caution/Monitor.atazanavirMonitor Closely (1)atazanavir increases levels of protriptyline by unspecified interaction mechanism. Use Caution/Monitor.atomoxetineMonitor Closely (1)atomoxetine and protriptyline both increase QTc interval. Use Caution/Monitor.atracuriumMonitor Closely (1)atracurium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.atropineMonitor Closely (1)atropine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)protriptyline increases levels of atropine by unknown mechanism. Minor/Significance Unknown.atropine IV/IMMonitor Closely (1)atropine IV/IM and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)protriptyline increases levels of atropine IV/IM by unknown mechanism. Minor/Significance Unknown.avapritinibMonitor Closely (1)avapritinib and protriptyline both increase sedation. Use Caution/Monitor.azelastineMonitor Closely (1)azelastine and protriptyline both increase sedation. Use Caution/Monitor.azithromycinMonitor Closely (1)protriptyline and azithromycin both increase QTc interval. Use Caution/Monitor.baclofenMonitor Closely (1)baclofen and protriptyline both increase sedation. Use Caution/Monitor.bazedoxifene/conjugated estrogensMinor (1)bazedoxifene/conjugated estrogens, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.bedaquilineMonitor Closely (1)protriptyline and bedaquiline both increase QTc interval. Modify Therapy/Monitor Closely. ECG should be monitored closelybelladonna alkaloidsMonitor Closely (1)belladonna alkaloids and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.belladonna and opiumMonitor Closely (2)belladonna and opium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. belladonna and opium and protriptyline both increase sedation. Use Caution/Monitor.benperidolMonitor Closely (1)benperidol and protriptyline both increase sedation. Use Caution/Monitor.benzhydrocodone/acetaminophenMonitor Closely (1)benzhydrocodone/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.Serious - Use Alternative (1)benzhydrocodone/acetaminophen and protriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequatebenzphetamineMonitor Closely (1)protriptyline increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, benzphetamine. 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.benztropineMonitor Closely (1)benztropine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.bethanecholMonitor Closely (1)bethanechol increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.brexpiprazoleMonitor Closely (1)brexpiprazole and protriptyline both increase sedation. Use Caution/Monitor.brimonidineMonitor Closely (1)brimonidine and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)protriptyline decreases effects of brimonidine by pharmacodynamic antagonism. Minor/Significance Unknown.brivaracetamMonitor Closely (1)brivaracetam and protriptyline both increase sedation. Use Caution/Monitor.brompheniramineMonitor Closely (1)brompheniramine and protriptyline both increase sedation. Use Caution/Monitor.buprenorphineMonitor Closely (1)buprenorphine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)buprenorphine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.buprenorphine buccalMonitor Closely (1)buprenorphine buccal and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)buprenorphine buccal and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.buprenorphine subdermal implantMonitor Closely (1)protriptyline, 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.Serious - Use Alternative (2)buprenorphine subdermal implant and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. buprenorphine subdermal implant and protriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequatebuprenorphine transdermalSerious - Use Alternative (2)buprenorphine transdermal and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. buprenorphine transdermal and protriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequatebuprenorphine, long-acting injectionMonitor Closely (1)protriptyline, 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.Serious - Use Alternative (2)buprenorphine, long-acting injection and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. buprenorphine, long-acting injection and protriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequatebupropionMonitor Closely (2)protriptyline 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.buspironeSerious - Use Alternative (1)protriptyline and buspirone both increase serotonin levels. Avoid or Use Alternate Drug.butabarbitalMonitor Closely (1)butabarbital and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)butabarbital, protriptyline. 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.butalbitalMonitor Closely (1)butalbital and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)butalbital, protriptyline. 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.butorphanolMonitor Closely (1)butorphanol and protriptyline both increase sedation. Use Caution/Monitor.caffeineMonitor Closely (1)protriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.calcium/magnesium/potassium/sodium oxybatesSerious - Use Alternative (1)protriptyline, calcium/magnesium/potassium/sodium oxybates. 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.carbacholMonitor Closely (1)carbachol increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.carbamazepineMinor (1)carbamazepine decreases levels of protriptyline by increasing metabolism. Minor/Significance Unknown.carbinoxamineMonitor Closely (1)carbinoxamine and protriptyline both increase sedation. Use Caution/Monitor.carisoprodolMonitor Closely (1)carisoprodol and protriptyline both increase sedation. Use Caution/Monitor.cenobamateMonitor Closely (1)cenobamate, protriptyline. Either increases effects of the other by sedation. Use Caution/Monitor.ceritinibMonitor Closely (1)ceritinib and protriptyline both increase QTc interval. Use Caution/Monitor.cevimelineMonitor Closely (1)cevimeline increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.chloral hydrateMonitor Closely (1)chloral hydrate and protriptyline both increase sedation. Use Caution/Monitor.chlordiazepoxideMonitor Closely (1)chlordiazepoxide and protriptyline both increase sedation. Use Caution/Monitor.chloroquineMinor (1)chloroquine increases toxicity of protriptyline by QTc interval. Minor/Significance Unknown.chlorpheniramineMonitor Closely (1)chlorpheniramine and protriptyline both increase sedation. Use Caution/Monitor.chlorpromazineMonitor Closely (1)chlorpromazine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)chlorpromazine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)protriptyline, chlorpromazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects. protriptyline, chlorpromazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.chlorpropamideMinor (1)protriptyline increases effects of chlorpropamide by pharmacodynamic synergism. Minor/Significance Unknown.chlorzoxazoneMonitor Closely (1)chlorzoxazone and protriptyline both increase sedation. Use Caution/Monitor.cinnarizineMonitor Closely (1)cinnarizine and protriptyline both increase sedation. Use Caution/Monitor.cisatracuriumMonitor Closely (1)cisatracurium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.citalopramSerious - Use Alternative (2)citalopram and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Citalopram may increase TCA levels. Increased risk of serotonin syndrome or neuroleptic malignant syndrome. Potential risk for QT prolongation. ECG monitoring is recommended. citalopram and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.clarithromycinSerious - Use Alternative (1)protriptyline and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug.clemastineMonitor Closely (1)clemastine and protriptyline both increase sedation. Use Caution/Monitor.clobazamMonitor Closely (2)clobazam 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).clomipramineMonitor Closely (2)clomipramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. clomipramine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)clomipramine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. clomipramine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.clonazepamMonitor Closely (1)clonazepam and protriptyline both increase sedation. Use Caution/Monitor.clonidineSerious - Use Alternative (1)protriptyline decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.clorazepateMonitor Closely (1)clorazepate and protriptyline both increase sedation. Use Caution/Monitor.clozapineMonitor Closely (2)clozapine and protriptyline both increase QTc interval. Use Caution/Monitor. clozapine and protriptyline both increase sedation. Use Caution/Monitor.cobicistatMonitor Closely (1)cobicistat 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