protriptyline (Rx)

Brand and Other Names:Vivactil

Dosing & Uses

AdultPediatricGeriatric

Depression

Initiate at low dose (10 mg/day) and gradually titrate upward every 5-7 days

15-60 mg/day PO divided q6-8hr; not to exceed 60 mg/day

Dosage Forms & Strengths

tablet

  • 5mg
  • 10mg

Depression

<12 years: Safety and efficacy not established

≥12 years: 15-20 mg PO qDay

See Black Box Warning

5 mg PO q8hr initially; increase by 5-10 mg q3-7days PRN; cardiovascular adverse effects may increase if doses exceed 20 mg/day

Next:

Interactions

Interaction Checker

and protriptyline

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            Contraindicated (15)

            • disopyramide

              protriptyline and disopyramide both increase QTc interval. Contraindicated.

            • ibutilide

              protriptyline and ibutilide both increase QTc interval. Contraindicated.

            • indapamide

              protriptyline and indapamide both increase QTc interval. Contraindicated.

            • iobenguane I 123

              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.

            • isocarboxazid

              isocarboxazid and protriptyline both increase serotonin levels. Contraindicated.

            • pentamidine

              protriptyline and pentamidine both increase QTc interval. Contraindicated.

            • phenelzine

              phenelzine and protriptyline both increase serotonin levels. Contraindicated.

            • pimozide

              protriptyline and pimozide both increase QTc interval. Contraindicated.

            • procainamide

              protriptyline and procainamide both increase QTc interval. Contraindicated.

            • procarbazine

              procarbazine and protriptyline both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI use.

            • quinidine

              quinidine and protriptyline both increase QTc interval. Contraindicated.

            • safinamide

              protriptyline, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

            • selegiline

              selegiline and protriptyline both increase serotonin levels. Contraindicated. Concurrent use or use within 14 days of selegiline treatment is contraindicated

            • sotalol

              protriptyline and sotalol both increase QTc interval. Contraindicated.

            • tranylcypromine

              tranylcypromine and protriptyline both increase serotonin levels. Contraindicated.

            Serious - Use Alternative (141)

            • adagrasib

              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.

            • albuterol

              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.

            • amiodarone

              protriptyline and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.

            • amitriptyline

              amitriptyline and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

              amitriptyline and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • amoxapine

              amoxapine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

              amoxapine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • apomorphine

              apomorphine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • arformoterol

              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.

            • arsenic trioxide

              protriptyline and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.

            • artemether

              artemether and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • artemether/lumefantrine

              protriptyline and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen and protriptyline both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

            • benzphetamine

              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.

            • buprenorphine

              buprenorphine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • buprenorphine buccal

              buprenorphine buccal and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • buprenorphine subdermal implant

              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 inadequate

            • buprenorphine transdermal

              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 inadequate

            • buprenorphine, long-acting injection

              buprenorphine, long-acting injection and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • buspirone

              protriptyline and buspirone both increase serotonin levels. Avoid or Use Alternate Drug.

            • calcium/magnesium/potassium/sodium oxybates

              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.

            • chlorpromazine

              chlorpromazine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • citalopram

              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.

            • clarithromycin

              protriptyline and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug.

            • clomipramine

              clomipramine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

              clomipramine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • clonidine

              protriptyline decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

            • cyclobenzaprine

              protriptyline and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug.

            • dacomitinib

              dacomitinib will increase the level or effect of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid use with CYP2D6 substrates where minimal increases in concentration of the CYP2D6 substrate may lead to serious or life-threatening toxicities.

            • desipramine

              desipramine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

              desipramine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • desvenlafaxine

              protriptyline and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

            • dexfenfluramine

              protriptyline, dexfenfluramine. 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.

            • dexmethylphenidate

              protriptyline, 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.

            • dextroamphetamine

              protriptyline, dextroamphetamine. 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.

            • dextromethorphan

              protriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

            • diethylpropion

              protriptyline, diethylpropion. 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.

            • dobutamine

              protriptyline, dobutamine. 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.

            • dofetilide

              protriptyline and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.

            • dolasetron

              dolasetron, protriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • dopamine

              protriptyline, dopamine. 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.

            • dopexamine

              protriptyline, dopexamine. 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.

            • doxepin

              doxepin and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

              doxepin and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • dronedarone

              protriptyline and dronedarone both increase QTc interval. Avoid or Use Alternate Drug.

            • droperidol

              protriptyline and droperidol both increase QTc interval. Avoid or Use Alternate Drug.

            • duloxetine

              duloxetine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • encorafenib

              encorafenib and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • ephedrine

              protriptyline, ephedrine. 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.

            • epinephrine

              epinephrine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

              protriptyline, epinephrine. 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.

            • epinephrine racemic

              epinephrine racemic and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

              protriptyline, epinephrine racemic. 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.

            • erythromycin base

              protriptyline and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin ethylsuccinate

              protriptyline and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin lactobionate

              protriptyline and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.

            • erythromycin stearate

              protriptyline and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.

            • escitalopram

              escitalopram and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • fenfluramine

              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.

            • fexinidazole

              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.

            • fluconazole

              protriptyline and fluconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • fluoxetine

              fluoxetine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • fluphenazine

              fluphenazine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • fluvoxamine

              fluvoxamine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • formoterol

              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.

            • fosamprenavir

              fosamprenavir increases levels of protriptyline by decreasing metabolism. Avoid or Use Alternate Drug.

            • givosiran

              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.

            • granisetron

              granisetron, protriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • guanfacine

              protriptyline decreases effects of guanfacine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

            • haloperidol

              protriptyline and haloperidol both increase QTc interval. Avoid or Use Alternate Drug.

            • hydroxychloroquine sulfate

              hydroxychloroquine sulfate and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • imipramine

              imipramine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

              imipramine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • iobenguane I 131

              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.

            • isoproterenol

              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.

            • itraconazole

              protriptyline and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • ivosidenib

              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.

            • ketoconazole

              protriptyline and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • levalbuterol

              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.

            • levoketoconazole

              protriptyline and levoketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

            • levomilnacipran

              levomilnacipran and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • linezolid

              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.

            • lisdexamfetamine

              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.

            • lofepramine

              lofepramine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

              lofepramine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • lorcaserin

              protriptyline and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.

            • lumefantrine

              protriptyline and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

            • macimorelin

              macimorelin and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. Macimorelin causes an increase of ~11 msec in the corrected QT interval. Avoid coadministration with drugs that prolong QT interval, which could increase risk for developing torsade de pointes-type ventricular tachycardia. Allow sufficient washout time of drugs that are known to prolong the QT interval before administering macimorelin.

            • maprotiline

              maprotiline and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

              maprotiline and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • mefloquine

              mefloquine increases toxicity of protriptyline by QTc interval. Avoid or Use Alternate Drug. Mefloquine may enhance the QTc prolonging effect of high risk QTc prolonging agents.

            • meperidine

              protriptyline and meperidine both increase serotonin levels. Avoid or Use Alternate Drug.

            • metaproterenol

              protriptyline, metaproterenol. 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.

            • methamphetamine

              protriptyline, methamphetamine. 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.

            • methylene blue

              methylene blue and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Methylene blue may increase serotonin as a result of MAO-A inhibition. If methylene blue must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last methylene blue dose or after 2 weeks of monitoring, whichever comes first.

            • methylenedioxymethamphetamine

              protriptyline, methylenedioxymethamphetamine. 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.

            • metoclopramide intranasal

              protriptyline, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

            • midodrine

              protriptyline, midodrine. 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.

            • milnacipran

              milnacipran and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • mirtazapine

              mirtazapine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • mobocertinib

              mobocertinib and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.

            • moxifloxacin

              protriptyline and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

            • nefazodone

              nefazodone and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • netupitant/palonosetron

              netupitant/palonosetron, protriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • nilotinib

              protriptyline and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.

            • norepinephrine

              protriptyline, norepinephrine. 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.

            • nortriptyline

              nortriptyline and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

              nortriptyline and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • octreotide

              protriptyline and octreotide both increase QTc interval. Avoid or Use Alternate Drug.

            • octreotide (Antidote)

              protriptyline and octreotide (Antidote) both increase QTc interval. Avoid or Use Alternate Drug.

            • olopatadine intranasal

              protriptyline and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

            • ondansetron

              protriptyline and ondansetron both increase QTc interval. Avoid or Use Alternate Drug. Avoid with congenital long QT syndrome; ECG monitoring recommended with concomitant medications that prolong QT interval, electrolyte abnormalities, CHF, or bradyarrhythmias.

              ondansetron, protriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • ozanimod

              ozanimod increases toxicity of protriptyline by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Because the active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis. Therefore, coadministration of ozanimod with drugs that can increase norepinephrine or serotonin is not recommended. Monitor for hypertension with concomitant use.

            • palonosetron

              palonosetron, protriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

            • paroxetine

              paroxetine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • perphenazine

              perphenazine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • phendimetrazine

              protriptyline, phendimetrazine. 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.

            • phentermine

              protriptyline, phentermine. 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.

            • phenylephrine

              protriptyline, phenylephrine. 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.

            • phenylephrine PO

              protriptyline, phenylephrine PO. 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.

            • pirbuterol

              protriptyline, pirbuterol. 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.

            • pitolisant

              protriptyline decreases effects of pitolisant by Other (see comment). Avoid or Use Alternate Drug. Comment: Pitolisant increases histamine levels in the brain; therefore, H1 receptor antagonists that cross the blood-brain barrier may reduce the efficacy of pitolisant.

            • promazine

              promazine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • propylhexedrine

              protriptyline, propylhexedrine. 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.

            • pseudoephedrine

              protriptyline increases effects of pseudoephedrine by sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • rasagiline

              rasagiline and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Severe CNS toxicity associated with hyperpyrexia has been reported with the combined treatment of an antidepressant and rasagiline. Avoid combination within 14 days of MAOI use.

            • ribociclib

              ribociclib increases toxicity of protriptyline by QTc interval. Avoid or Use Alternate Drug.

            • salmeterol

              protriptyline, 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.

            • selegiline transdermal

              selegiline transdermal and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • selinexor

              selinexor, protriptyline. 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.

            • serdexmethylphenidate/dexmethylphenidate

              protriptyline, 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.

            • sertraline

              sertraline and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

              sertraline and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • sodium oxybate

              protriptyline, 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.

            • St John's Wort

              protriptyline and St John's Wort both increase serotonin levels. Avoid or Use Alternate Drug.

            • tacrolimus

              tacrolimus and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • tedizolid

              tedizolid, protriptyline. Either increases effects of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. both increase serotonin levels; increased risk of serotonin syndrome.

            • terbutaline

              protriptyline, terbutaline. 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.

            • thioridazine

              thioridazine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • trazodone

              protriptyline and trazodone both increase QTc interval. Avoid or Use Alternate Drug.

              trazodone and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • trifluoperazine

              trifluoperazine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

            • trimipramine

              protriptyline and trimipramine both increase QTc interval. Avoid or Use Alternate Drug.

              protriptyline and trimipramine both increase serotonin levels. Avoid or Use Alternate Drug.

            • umeclidinium bromide/vilanterol inhaled

              protriptyline increases toxicity of umeclidinium bromide/vilanterol inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.

              protriptyline and umeclidinium bromide/vilanterol inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Exercise extreme caution if vilanterol coadministered with MAOIs or TCAs, or within 2 weeks of discontinuation of these drugs; adrenergic agonist effects on the cardiovascular system may be potentiated

            • vandetanib

              protriptyline, vandetanib. Either increases toxicity of the other by QTc interval. Avoid or Use Alternate Drug. Avoid coadministration with drugs known to prolong QT interval; if a drug known to prolong QT interval must be used, more frequent ECG monitoring is recommended.

            • vemurafenib

              vemurafenib and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. Concomitant use of vemurafenib with drugs that prolong QT interval is not recommended.

            • venlafaxine

              venlafaxine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

            • vilanterol/fluticasone furoate inhaled

              protriptyline and vilanterol/fluticasone furoate inhaled both increase sympathetic (adrenergic) effects, including increased blood pressure and heart rate. Avoid or Use Alternate Drug. Exercise extreme caution if vilanterol coadministered with MAOIs or TCAs, or within 2 weeks of discontinuation of these drugs; adrenergic agonist effects on the cardiovascular system may be potentiated

              protriptyline increases toxicity of vilanterol/fluticasone furoate inhaled by QTc interval. Avoid or Use Alternate Drug. Exercise extreme caution when vilanterol coadministered with drugs that prolong QTc interval; adrenergic agonist effects on the cardiovascular system may be potentiated.

            • vilazodone

              protriptyline, vilazodone. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug. Concomitant therapy should be discontinued immediately if signs or symptoms of serotonin syndrome emerge and supportive symptomatic treatment should be initiated. .

            • vortioxetine

              protriptyline, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.

            • xylometazoline

              protriptyline, xylometazoline. 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.

            • yohimbe

              yohimbe, protriptyline. Mechanism: unspecified interaction mechanism. Contraindicated. May cause increase or decrease in blood pressure.

            • yohimbine

              protriptyline, yohimbine. 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.

            • ziprasidone

              protriptyline and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.

            Monitor Closely (347)

            • 5-HTP

              protriptyline and 5-HTP both increase serotonin levels. Modify Therapy/Monitor Closely.

            • abiraterone

              abiraterone increases levels of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Avoid coadministration of abiraterone with substrates of CYP2D6. If alternative therapy cannot be used, exercise caution and consider a dose reduction of the CYP2D6 substrate.

            • abobotulinumtoxinA

              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. .

            • aclidinium

              aclidinium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • acrivastine

              acrivastine and protriptyline both increase sedation. Use Caution/Monitor.

            • albuterol

              protriptyline increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              albuterol and protriptyline both increase QTc interval. Use Caution/Monitor.

            • alfentanil

              alfentanil and protriptyline both increase sedation. Use Caution/Monitor.

            • alfuzosin

              protriptyline and alfuzosin both increase QTc interval. Use Caution/Monitor.

              alfuzosin and protriptyline both increase QTc interval. Use Caution/Monitor.

            • almotriptan

              almotriptan and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

            • alprazolam

              alprazolam and protriptyline both increase sedation. Use Caution/Monitor.

            • amifampridine

              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.

            • amisulpride

              protriptyline and amisulpride both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended if coadministered.

            • amitriptyline

              amitriptyline and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              amitriptyline and protriptyline both increase sedation. Use Caution/Monitor.

            • amobarbital

              amobarbital and protriptyline both increase sedation. Use Caution/Monitor.

            • amoxapine

              amoxapine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              amoxapine and protriptyline both increase sedation. Use Caution/Monitor.

            • anagrelide

              anagrelide and protriptyline both increase QTc interval. Use Caution/Monitor.

            • anticholinergic/sedative combos

              anticholinergic/sedative combos and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • apomorphine

              protriptyline and apomorphine both increase sedation. Use Caution/Monitor.

            • arformoterol

              protriptyline 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.

            • aripiprazole

              aripiprazole and protriptyline both increase sedation. Use Caution/Monitor.

            • armodafinil

              protriptyline increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • asenapine

              asenapine and protriptyline both increase QTc interval. Use Caution/Monitor.

              asenapine and protriptyline both increase sedation. Use Caution/Monitor.

            • asenapine transdermal

              asenapine transdermal and protriptyline both increase QTc interval. Use Caution/Monitor.

              asenapine transdermal and protriptyline both increase sedation. Use Caution/Monitor.

            • atazanavir

              atazanavir increases levels of protriptyline by unspecified interaction mechanism. Use Caution/Monitor.

            • atomoxetine

              atomoxetine and protriptyline both increase QTc interval. Use Caution/Monitor.

            • atracurium

              atracurium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • atropine

              atropine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • atropine IV/IM

              atropine IV/IM and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • avapritinib

              avapritinib and protriptyline both increase sedation. Use Caution/Monitor.

            • azelastine

              azelastine and protriptyline both increase sedation. Use Caution/Monitor.

            • azithromycin

              protriptyline and azithromycin both increase QTc interval. Use Caution/Monitor.

            • baclofen

              baclofen and protriptyline both increase sedation. Use Caution/Monitor.

            • bedaquiline

              protriptyline and bedaquiline both increase QTc interval. Modify Therapy/Monitor Closely. ECG should be monitored closely

            • belladonna alkaloids

              belladonna alkaloids and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • belladonna and opium

              belladonna and opium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              belladonna and opium and protriptyline both increase sedation. Use Caution/Monitor.

            • benperidol

              benperidol and protriptyline both increase sedation. Use Caution/Monitor.

            • benzhydrocodone/acetaminophen

              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.

            • benzphetamine

              protriptyline increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • benztropine

              benztropine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • bethanechol

              bethanechol increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • brexpiprazole

              brexpiprazole and protriptyline both increase sedation. Use Caution/Monitor.

            • brimonidine

              brimonidine and protriptyline both increase sedation. Use Caution/Monitor.

            • brivaracetam

              brivaracetam and protriptyline both increase sedation. Use Caution/Monitor.

            • brompheniramine

              brompheniramine and protriptyline both increase sedation. Use Caution/Monitor.

            • buprenorphine

              buprenorphine and protriptyline both increase sedation. Use Caution/Monitor.

            • buprenorphine buccal

              buprenorphine buccal and protriptyline both increase sedation. Use Caution/Monitor.

            • buprenorphine subdermal implant

              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.

            • buprenorphine, long-acting injection

              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.

            • bupropion

              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.

            • butabarbital

              butabarbital and protriptyline both increase sedation. Use Caution/Monitor.

            • butalbital

              butalbital and protriptyline both increase sedation. Use Caution/Monitor.

            • butorphanol

              butorphanol and protriptyline both increase sedation. Use Caution/Monitor.

            • caffeine

              protriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • carbachol

              carbachol increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • carbinoxamine

              carbinoxamine and protriptyline both increase sedation. Use Caution/Monitor.

            • carisoprodol

              carisoprodol and protriptyline both increase sedation. Use Caution/Monitor.

            • cenobamate

              cenobamate, protriptyline. Either increases effects of the other by sedation. Use Caution/Monitor.

            • ceritinib

              ceritinib and protriptyline both increase QTc interval. Use Caution/Monitor.

            • cevimeline

              cevimeline increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • chloral hydrate

              chloral hydrate and protriptyline both increase sedation. Use Caution/Monitor.

            • chlordiazepoxide

              chlordiazepoxide and protriptyline both increase sedation. Use Caution/Monitor.

            • chlorpheniramine

              chlorpheniramine and protriptyline both increase sedation. Use Caution/Monitor.

            • chlorpromazine

              chlorpromazine and protriptyline both increase sedation. Use Caution/Monitor.

            • chlorzoxazone

              chlorzoxazone and protriptyline both increase sedation. Use Caution/Monitor.

            • cinnarizine

              cinnarizine and protriptyline both increase sedation. Use Caution/Monitor.

            • cisatracurium

              cisatracurium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • clemastine

              clemastine and protriptyline both increase sedation. Use Caution/Monitor.

            • clobazam

              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).

            • clomipramine

              clomipramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              clomipramine and protriptyline both increase sedation. Use Caution/Monitor.

            • clonazepam

              clonazepam and protriptyline both increase sedation. Use Caution/Monitor.

            • clorazepate

              clorazepate and protriptyline both increase sedation. Use Caution/Monitor.

            • clozapine

              clozapine and protriptyline both increase sedation. Use Caution/Monitor.

              clozapine and protriptyline both increase QTc interval. Use Caution/Monitor.

            • cobicistat

              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 feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.

            • cocaine topical

              protriptyline and cocaine topical both increase serotonin levels. Modify Therapy/Monitor Closely.

            • codeine

              codeine and protriptyline both increase sedation. Use Caution/Monitor.

            • crizotinib

              crizotinib and protriptyline both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

            • cyclizine

              cyclizine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              cyclizine and protriptyline both increase sedation. Use Caution/Monitor.

            • cyclobenzaprine

              cyclobenzaprine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              cyclobenzaprine and protriptyline both increase sedation. Use Caution/Monitor.

            • cyproheptadine

              cyproheptadine and protriptyline both increase sedation. Use Caution/Monitor.

            • dantrolene

              dantrolene and protriptyline both increase sedation. Use Caution/Monitor.

            • daridorexant

              protriptyline 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.

            • darifenacin

              darifenacin and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • dasatinib

              protriptyline and dasatinib both increase QTc interval. Modify Therapy/Monitor Closely.

            • debrisoquine

              protriptyline decreases effects of debrisoquine by Other (see comment). Use Caution/Monitor. Comment: Inhibition of uptake by adrenergic neurons.

            • degarelix

              degarelix and protriptyline both increase QTc interval. Use Caution/Monitor.

            • desflurane

              desflurane and protriptyline both increase sedation. Use Caution/Monitor.

              desflurane and protriptyline both increase QTc interval. Use Caution/Monitor.

            • desipramine

              desipramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              desipramine and protriptyline both increase sedation. Use Caution/Monitor.

            • deutetrabenazine

              protriptyline 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).

            • dexchlorpheniramine

              dexchlorpheniramine and protriptyline both increase sedation. Use Caution/Monitor.

            • dexfenfluramine

              protriptyline 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.

            • dexmedetomidine

              dexmedetomidine and protriptyline both increase sedation. Use Caution/Monitor.

            • dexmethylphenidate

              protriptyline increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dextroamphetamine

              protriptyline 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 transdermal

              protriptyline 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.

            • dextromoramide

              dextromoramide and protriptyline both increase sedation. Use Caution/Monitor.

            • diamorphine

              diamorphine and protriptyline both increase sedation. Use Caution/Monitor.

            • diazepam

              diazepam and protriptyline both increase sedation. Use Caution/Monitor.

            • diazepam intranasal

              diazepam intranasal, protriptyline. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration may potentiate the CNS-depressant effects of each drug.

            • dicyclomine

              dicyclomine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • diethylpropion

              protriptyline increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • difelikefalin

              difelikefalin and protriptyline both increase sedation. Use Caution/Monitor.

            • difenoxin hcl

              difenoxin hcl and protriptyline both increase sedation. Use Caution/Monitor.

            • dihydroergotamine

              protriptyline and dihydroergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • dihydroergotamine intranasal

              protriptyline and dihydroergotamine intranasal both increase serotonin levels. Modify Therapy/Monitor Closely.

            • dimenhydrinate

              dimenhydrinate and protriptyline both increase sedation. Use Caution/Monitor.

            • diphenhydramine

              diphenhydramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              diphenhydramine and protriptyline both increase sedation. Use Caution/Monitor.

            • diphenoxylate hcl

              diphenoxylate hcl and protriptyline both increase sedation. Use Caution/Monitor.

            • dipipanone

              dipipanone and protriptyline both increase sedation. Use Caution/Monitor.

            • dobutamine

              protriptyline increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dofetilide

              dofetilide increases toxicity of protriptyline by QTc interval. Use Caution/Monitor.

            • dolasetron

              protriptyline and dolasetron both increase QTc interval. Modify Therapy/Monitor Closely.

            • donepezil

              donepezil 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.

            • dopamine

              protriptyline increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dopexamine

              protriptyline increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • doxepin

              doxepin and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              doxepin and protriptyline both increase sedation. Use Caution/Monitor.

            • doxylamine

              doxylamine and protriptyline both increase sedation. Use Caution/Monitor.

            • droperidol

              droperidol and protriptyline both increase sedation. Use Caution/Monitor.

            • echothiophate iodide

              echothiophate iodide increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • efavirenz

              efavirenz and protriptyline both increase QTc interval. Use Caution/Monitor.

            • eletriptan

              eletriptan and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

            • eliglustat

              eliglustat 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 DF

              elvitegravir/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.

            • entrectinib

              entrectinib and protriptyline both increase QTc interval. Use Caution/Monitor.

            • ephedrine

              protriptyline 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.

            • epinephrine

              protriptyline 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 inhaled

              protriptyline 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 racemic

              protriptyline 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.

            • ergotamine

              protriptyline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • eribulin

              eribulin and protriptyline both increase QTc interval. Use Caution/Monitor.

            • escitalopram

              escitalopram increases toxicity of protriptyline by QTc interval. Use Caution/Monitor.

            • esketamine intranasal

              esketamine intranasal, protriptyline. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

            • estazolam

              estazolam and protriptyline both increase sedation. Use Caution/Monitor.

            • ethanol

              protriptyline and ethanol both increase sedation. Use Caution/Monitor.

            • etomidate

              etomidate and protriptyline both increase sedation. Use Caution/Monitor.

            • ezogabine

              ezogabine, 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.

            • fedratinib

              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.

            • fenfluramine

              protriptyline 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.

            • fesoterodine

              fesoterodine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • fingolimod

              fingolimod and protriptyline both increase QTc interval. Use Caution/Monitor.

            • flavoxate

              flavoxate and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • flecainide

              protriptyline and flecainide both increase QTc interval. Modify Therapy/Monitor Closely.

            • fluoxetine

              protriptyline and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely.

            • fluphenazine

              fluphenazine and protriptyline both increase sedation. Use Caution/Monitor.

            • flurazepam

              flurazepam and protriptyline both increase sedation. Use Caution/Monitor.

            • fluvoxamine

              fluvoxamine and protriptyline both increase QTc interval. Modify Therapy/Monitor Closely.

            • formoterol

              protriptyline increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • foscarnet

              protriptyline and foscarnet both increase QTc interval. Modify Therapy/Monitor Closely.

            • frovatriptan

              frovatriptan and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

            • gabapentin

              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 enacarbil

              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.

            • galantamine

              galantamine increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ganaxolone

              protriptyline and ganaxolone both increase sedation. Use Caution/Monitor.

            • gemifloxacin

              gemifloxacin and protriptyline both increase QTc interval. Use Caution/Monitor.

            • gilteritinib

              gilteritinib and protriptyline both increase QTc interval. Use Caution/Monitor.

            • glycopyrrolate

              glycopyrrolate and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              protriptyline increases levels of glycopyrrolate by unknown mechanism. Use Caution/Monitor.

            • glycopyrrolate inhaled

              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 topical

              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.

            • granisetron

              granisetron and protriptyline both increase QTc interval. Use Caution/Monitor.

            • haloperidol

              haloperidol and protriptyline both increase sedation. Use Caution/Monitor.

            • henbane

              henbane and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • homatropine

              homatropine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • huperzine A

              huperzine A increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • hydrocodone

              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.

            • hydromorphone

              hydromorphone and protriptyline both increase sedation. Use Caution/Monitor.

            • hydroxyzine

              hydroxyzine and protriptyline both increase sedation. Use Caution/Monitor.

              hydroxyzine and protriptyline both increase QTc interval. Use Caution/Monitor.

            • hyoscyamine

              hyoscyamine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • hyoscyamine spray

              hyoscyamine spray and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • iloperidone

              protriptyline and iloperidone both increase QTc interval. Modify Therapy/Monitor Closely.

              iloperidone and protriptyline both increase sedation. Use Caution/Monitor.

            • imipramine

              imipramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              imipramine and protriptyline both increase sedation. Use Caution/Monitor.

            • indacaterol, inhaled

              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.

            • ipratropium

              ipratropium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • isoflurane

              isoflurane and protriptyline both increase QTc interval. Use Caution/Monitor.

            • isoniazid

              protriptyline and isoniazid both increase serotonin levels. Modify Therapy/Monitor Closely.

            • isoproterenol

              protriptyline increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ketamine

              ketamine and protriptyline both increase sedation. Use Caution/Monitor.

            • ketotifen, ophthalmic

              protriptyline and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

            • L-tryptophan

              protriptyline and L-tryptophan both increase serotonin levels. Modify Therapy/Monitor Closely.

            • lapatinib

              protriptyline and lapatinib both increase QTc interval. Modify Therapy/Monitor Closely.

            • lasmiditan

              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.

            • lemborexant

              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.

            • levalbuterol

              protriptyline increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • levofloxacin

              protriptyline and levofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

            • levorphanol

              levorphanol and protriptyline both increase sedation. Use Caution/Monitor.

            • levothyroxine

              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.

            • liothyronine

              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.

            • liotrix

              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.

            • lisdexamfetamine

              protriptyline increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              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).

            • lithium

              protriptyline and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.

              lithium and protriptyline both increase QTc interval. Use Caution/Monitor.

            • lofepramine

              lofepramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              lofepramine and protriptyline both increase sedation. Use Caution/Monitor.

            • lofexidine

              protriptyline and lofexidine both increase sedation. Use Caution/Monitor.

              protriptyline decreases effects of lofexidine by unspecified interaction mechanism. Use Caution/Monitor.

            • loprazolam

              loprazolam and protriptyline both increase sedation. Use Caution/Monitor.

            • lorazepam

              lorazepam and protriptyline both increase sedation. Use Caution/Monitor.

            • lorcaserin

              lorcaserin will increase the level or effect of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • lormetazepam

              lormetazepam and protriptyline both increase sedation. Use Caution/Monitor.

            • loxapine

              loxapine and protriptyline both increase sedation. Use Caution/Monitor.

            • loxapine inhaled

              loxapine inhaled and protriptyline both increase sedation. Use Caution/Monitor.

            • lsd

              protriptyline and lsd both increase serotonin levels. Modify Therapy/Monitor Closely.

            • lurasidone

              lurasidone, protriptyline. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for additive CNS effects .

            • maprotiline

              maprotiline and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              maprotiline and protriptyline both increase sedation. Use Caution/Monitor.

            • marijuana

              protriptyline and marijuana both increase sedation. Use Caution/Monitor.

            • meclizine

              meclizine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • melatonin

              protriptyline and melatonin both increase sedation. Use Caution/Monitor.

            • meperidine

              meperidine and protriptyline both increase sedation. Use Caution/Monitor.

            • meprobamate

              protriptyline and meprobamate both increase sedation. Use Caution/Monitor.

            • metaproterenol

              protriptyline increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • metaxalone

              metaxalone and protriptyline both increase sedation. Use Caution/Monitor.

            • methadone

              protriptyline and methadone both increase QTc interval. Modify Therapy/Monitor Closely.

              methadone and protriptyline both increase sedation. Use Caution/Monitor.

            • methamphetamine

              protriptyline increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • methocarbamol

              methocarbamol and protriptyline both increase sedation. Use Caution/Monitor.

            • methscopolamine

              methscopolamine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • methylenedioxymethamphetamine

              protriptyline increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • methylphenidate

              protriptyline, methylphenidate. Other (see comment). Use Caution/Monitor. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • methylphenidate transdermal

              methylphenidate transdermal will increase the level or effect of protriptyline by decreasing elimination. Modify Therapy/Monitor Closely. Consider decreasing the dose of these drugs when given coadministered with methylphenidate. Monitor for drug toxiticities when initiating or discontinuing methylphenidate.

            • midazolam

              midazolam and protriptyline both increase sedation. Use Caution/Monitor.

            • midodrine

              protriptyline increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • mifepristone

              mifepristone, protriptyline. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.

            • mirabegron

              mirabegron will increase the level or effect of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • mirtazapine

              protriptyline and mirtazapine both increase sedation. Use Caution/Monitor.

              protriptyline and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • modafinil

              protriptyline increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • morphine

              morphine and protriptyline both increase sedation. Use Caution/Monitor.

              protriptyline and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • motherwort

              protriptyline and motherwort both increase sedation. Use Caution/Monitor.

            • moxonidine

              protriptyline and moxonidine both increase sedation. Use Caution/Monitor.

            • nabilone

              protriptyline and nabilone both increase sedation. Use Caution/Monitor.

            • nalbuphine

              nalbuphine and protriptyline both increase sedation. Use Caution/Monitor.

            • naratriptan

              naratriptan and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

            • nefopam

              nefopam, protriptyline. Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Use combination with caution.

            • neostigmine

              neostigmine increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • norepinephrine

              protriptyline increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              protriptyline increases effects of norepinephrine by unknown mechanism. Use Caution/Monitor.

            • nortriptyline

              nortriptyline and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              nortriptyline and protriptyline both increase sedation. Use Caution/Monitor.

            • ofloxacin

              protriptyline and ofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

            • olanzapine

              olanzapine and protriptyline both increase sedation. Use Caution/Monitor.

              olanzapine and protriptyline both increase QTc interval. Use Caution/Monitor.

            • oliceridine

              protriptyline, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely.

              protriptyline increases toxicity of oliceridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor for signs of urinary retention or reduced gastric motility if oliceridine is coadministered with anticholinergics.

            • olodaterol inhaled

              protriptyline and olodaterol inhaled both increase QTc interval. Use Caution/Monitor. TCAs prolong the QTc interval and may potentiate the effects of beta2 agonists on the cardiovascular system; increased risk of ventricular arrhythmias

            • onabotulinumtoxinA

              onabotulinumtoxinA and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • opium tincture

              opium tincture and protriptyline both increase sedation. Use Caution/Monitor.

            • orphenadrine

              protriptyline and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

              orphenadrine and protriptyline both increase sedation. Use Caution/Monitor.

            • osimertinib

              osimertinib and protriptyline both increase QTc interval. Use Caution/Monitor. Conduct periodic monitoring with ECGs and electrolytes in patients taking drugs known to prolong the QTc interval.

            • oxazepam

              oxazepam and protriptyline both increase sedation. Use Caution/Monitor.

            • oxybutynin

              oxybutynin and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • oxybutynin topical

              oxybutynin topical and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • oxybutynin transdermal

              oxybutynin transdermal and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • oxycodone

              oxycodone and protriptyline both increase sedation. Use Caution/Monitor.

            • oxymetazoline intranasal

              protriptyline increases effects of oxymetazoline intranasal by pharmacodynamic synergism. Use Caution/Monitor. TCAs inhibit norepinephrine uptake in adrenergic neurons, thereby increasing synaptic norepinephrine levels. Coadministration with alpha1 agonists may cause increased adrenergic receptor stimulation. When oxymetazoline is combined with intranasal tetracaine for dental anesthesia, avoid or use alternant anesthetic in patients taking TCAs.

            • oxymorphone

              oxymorphone and protriptyline both increase sedation. Use Caution/Monitor.

            • ozanimod

              ozanimod and protriptyline both increase QTc interval. Modify Therapy/Monitor Closely. The potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT prolonging drugs with known arrhythmogenic properties.

            • paliperidone

              protriptyline and paliperidone both increase QTc interval. Modify Therapy/Monitor Closely.

              paliperidone and protriptyline both increase sedation. Use Caution/Monitor.

            • pancuronium

              pancuronium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • papaveretum

              papaveretum and protriptyline both increase sedation. Use Caution/Monitor.

            • papaverine

              protriptyline and papaverine both increase sedation. Use Caution/Monitor.

            • paroxetine

              protriptyline and paroxetine both increase QTc interval. Modify Therapy/Monitor Closely.

            • pasireotide

              protriptyline and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.

            • pazopanib

              protriptyline and pazopanib both increase QTc interval. Use Caution/Monitor.

            • peginterferon alfa 2b

              peginterferon alfa 2b, protriptyline. Other (see comment). Use Caution/Monitor. Comment: When patients are administered peginterferon alpha-2b with CYP2D6 substrates, the therapeutic effect of these drugs may be altered. Peginterferon alpha-2b may increase or decrease levels of CYP2D6 substrate.

            • pentazocine

              pentazocine and protriptyline both increase sedation. Use Caution/Monitor.

              protriptyline and pentazocine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • pentobarbital

              pentobarbital and protriptyline both increase sedation. Use Caution/Monitor.

            • perphenazine

              perphenazine and protriptyline both increase sedation. Use Caution/Monitor.

            • phendimetrazine

              protriptyline increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenobarbital

              phenobarbital and protriptyline both increase sedation. Use Caution/Monitor.

            • phentermine

              protriptyline increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenylephrine

              protriptyline increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenylephrine ophthalmic

              protriptyline, phenylephrine ophthalmic. Other (see comment). Use Caution/Monitor. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

            • phenylephrine PO

              protriptyline increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

            • pholcodine

              protriptyline and pholcodine both increase sedation. Use Caution/Monitor.

            • physostigmine

              physostigmine increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pilocarpine

              pilocarpine increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pimozide

              pimozide and protriptyline both increase sedation. Use Caution/Monitor.

            • pirbuterol

              protriptyline increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • posaconazole

              protriptyline and posaconazole both increase QTc interval. Modify Therapy/Monitor Closely.

            • pralidoxime

              pralidoxime and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • pregabalin

              pregabalin, 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.

            • primidone

              primidone and protriptyline both increase sedation. Use Caution/Monitor.

            • prochlorperazine

              prochlorperazine and protriptyline both increase QTc interval. Use Caution/Monitor.

              prochlorperazine and protriptyline both increase sedation. Use Caution/Monitor.

            • promethazine

              promethazine and protriptyline both increase QTc interval. Use Caution/Monitor.

              promethazine and protriptyline both increase sedation. Use Caution/Monitor.

            • propantheline

              propantheline and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • propofol

              propofol and protriptyline both increase sedation. Use Caution/Monitor.

            • propylhexedrine

              protriptyline increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pyridostigmine

              pyridostigmine increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • quazepam

              quazepam and protriptyline both increase sedation. Use Caution/Monitor.

            • quetiapine

              quetiapine and protriptyline both increase sedation. Use Caution/Monitor.

              quetiapine, protriptyline. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Avoid use with drugs that prolong QT and in patients with risk factors for prolonged QT interval. Postmarketing cases show QT prolongation with overdose in patients with concomitant illness or with drugs known to cause electrolyte imbalance or prolong QT.

            • quinine

              protriptyline and quinine both increase QTc interval. Use Caution/Monitor.

            • ramelteon

              protriptyline and ramelteon both increase sedation. Use Caution/Monitor.

            • ranolazine

              protriptyline and ranolazine both increase QTc interval. Modify Therapy/Monitor Closely.

            • rapacuronium

              rapacuronium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • remimazolam

              remimazolam, protriptyline. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely. Coadministration may result in profound sedation, respiratory depression, coma, and/or death. Continuously monitor vital signs during sedation and recovery period if coadministered. Carefully titrate remimazolam dose if administered with opioid analgesics and/or sedative/hypnotics.

            • rifabutin

              rifabutin decreases levels of protriptyline by increasing metabolism. Use Caution/Monitor.

            • rilpivirine

              rilpivirine increases toxicity of protriptyline by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsade de Pointes.

            • risperidone

              protriptyline and risperidone both increase QTc interval. Modify Therapy/Monitor Closely.

              risperidone and protriptyline both increase sedation. Use Caution/Monitor.

            • rivastigmine

              rivastigmine increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • rizatriptan

              rizatriptan and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

            • rocuronium

              rocuronium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • rolapitant

              rolapitant will increase the level or effect of protriptyline 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.

            • romidepsin

              protriptyline and romidepsin both increase QTc interval. Modify Therapy/Monitor Closely.

            • salmeterol

              protriptyline increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • SAMe

              protriptyline and SAMe both increase serotonin levels. Modify Therapy/Monitor Closely.

            • scopolamine

              scopolamine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • scullcap

              protriptyline and scullcap both increase sedation. Use Caution/Monitor.

            • secobarbital

              secobarbital and protriptyline both increase sedation. Use Caution/Monitor.

            • selpercatinib

              selpercatinib increases toxicity of protriptyline by QTc interval. Use Caution/Monitor.

            • sevoflurane

              sevoflurane and protriptyline both increase sedation. Use Caution/Monitor.

              sevoflurane and protriptyline both increase QTc interval. Use Caution/Monitor.

            • shepherd's purse

              protriptyline and shepherd's purse both increase sedation. Use Caution/Monitor.

            • sodium sulfate/?magnesium sulfate/potassium chloride

              sodium sulfate/?magnesium sulfate/potassium chloride increases effects of protriptyline 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

              sodium sulfate/potassium sulfate/magnesium sulfate increases effects of protriptyline 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/polyethylene glycol

              protriptyline, sodium sulfate/potassium sulfate/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.

            • solifenacin

              solifenacin and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

              solifenacin and protriptyline both increase QTc interval. Use Caution/Monitor.

            • sorafenib

              sorafenib and protriptyline both increase QTc interval. Use Caution/Monitor.

            • stiripentol

              stiripentol, protriptyline. 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.

            • succinylcholine

              succinylcholine increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • sufentanil

              sufentanil and protriptyline both increase sedation. Use Caution/Monitor.

            • sufentanil SL

              sufentanil SL, 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.

            • sulfamethoxazole

              protriptyline and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.

            • sumatriptan

              sumatriptan and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

            • sumatriptan intranasal

              sumatriptan intranasal and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

            • suvorexant

              suvorexant and protriptyline both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary

            • tapentadol

              tapentadol and protriptyline both increase sedation. Use Caution/Monitor.

              protriptyline and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.

            • telavancin

              protriptyline and telavancin both increase QTc interval. Modify Therapy/Monitor Closely.

            • temazepam

              temazepam and protriptyline both increase sedation. Use Caution/Monitor.

            • terbinafine

              terbinafine will increase the level or effect of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.

            • terbutaline

              protriptyline increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • tetrabenazine

              tetrabenazine and protriptyline both increase QTc interval. Use Caution/Monitor.

            • thioridazine

              thioridazine and protriptyline both increase sedation. Use Caution/Monitor.

            • thiothixene

              thiothixene and protriptyline both increase sedation. Use Caution/Monitor.

            • thyroid desiccated

              thyroid desiccated increases effects of protriptyline by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

            • tiotropium

              tiotropium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • tolterodine

              tolterodine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • topiramate

              protriptyline and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • tramadol

              tramadol and protriptyline both increase sedation. Use Caution/Monitor.

              protriptyline and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

            • trazodone

              protriptyline and trazodone both decrease cholinergic effects/transmission. Use Caution/Monitor.

              protriptyline and trazodone both increase sedation. Use Caution/Monitor.

            • triazolam

              triazolam and protriptyline both increase sedation. Use Caution/Monitor.

            • triclofos

              triclofos and protriptyline both increase sedation. Use Caution/Monitor.

            • trifluoperazine

              trifluoperazine and protriptyline both increase sedation. Use Caution/Monitor.

            • trihexyphenidyl

              trihexyphenidyl and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. Potential for additive anticholinergic effects.

            • trimethoprim

              protriptyline and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

            • trimipramine

              protriptyline and trimipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

              protriptyline and trimipramine both increase sedation. Use Caution/Monitor.

            • triprolidine

              triprolidine and protriptyline both increase sedation. Use Caution/Monitor.

            • tropisetron

              protriptyline and tropisetron both increase QTc interval. Modify Therapy/Monitor Closely.

            • trospium chloride

              trospium chloride and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • valbenazine

              valbenazine and protriptyline both increase QTc interval. Use Caution/Monitor.

            • valerian

              valerian and protriptyline both increase sedation. Use Caution/Monitor.

            • vecuronium

              vecuronium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • venlafaxine

              protriptyline and venlafaxine both increase QTc interval. Modify Therapy/Monitor Closely.

            • voclosporin

              voclosporin, protriptyline. Either increases effects of the other by QTc interval. Use Caution/Monitor.

            • voriconazole

              protriptyline and voriconazole both increase QTc interval. Modify Therapy/Monitor Closely.

            • xylometazoline

              protriptyline increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • yohimbine

              protriptyline increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ziconotide

              protriptyline and ziconotide both increase sedation. Use Caution/Monitor.

            • ziprasidone

              ziprasidone and protriptyline both increase sedation. Use Caution/Monitor.

            • zolmitriptan

              zolmitriptan and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

            Minor (71)

            • acarbose

              protriptyline increases effects of acarbose by pharmacodynamic synergism. Minor/Significance Unknown.

            • amobarbital

              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.

            • atropine

              protriptyline increases levels of atropine by unknown mechanism. Minor/Significance Unknown.

            • atropine IV/IM

              protriptyline increases levels of atropine IV/IM by unknown mechanism. Minor/Significance Unknown.

            • bazedoxifene/conjugated estrogens

              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.

            • brimonidine

              protriptyline decreases effects of brimonidine by pharmacodynamic antagonism. Minor/Significance Unknown.

            • butabarbital

              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.

            • butalbital

              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.

            • carbamazepine

              carbamazepine decreases levels of protriptyline by increasing metabolism. Minor/Significance Unknown.

            • chloroquine

              chloroquine increases toxicity of protriptyline by QTc interval. Minor/Significance Unknown.

            • chlorpromazine

              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.

            • chlorpropamide

              protriptyline increases effects of chlorpropamide by pharmacodynamic synergism. Minor/Significance Unknown.

            • conjugated estrogens

              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.

            • conjugated estrogens, vaginal

              conjugated estrogens, vaginal, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • desflurane

              desflurane, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

            • dexmethylphenidate

              dexmethylphenidate increases effects of protriptyline by decreasing metabolism. Minor/Significance Unknown.

            • estradiol

              estradiol, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • estrogens conjugated synthetic

              estrogens conjugated synthetic, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • estrogens esterified

              estrogens esterified, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens may inhibit hepatic metabolism of tricyclic antidepressants. However, interactions are not common.

            • estropipate

              estropipate, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • ethinylestradiol

              ethinylestradiol, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Oxidative metabolism of TCAs may be decreased by ethinyl estradiol. Increased antidepressant serum concentrations may occur. Potential for increased TCA adverse effects.

            • etomidate

              etomidate, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

            • eucalyptus

              protriptyline and eucalyptus both increase sedation. Minor/Significance Unknown.

            • fluphenazine

              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.

            • glimepiride

              protriptyline increases effects of glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.

            • glipizide

              protriptyline increases effects of glipizide by pharmacodynamic synergism. Minor/Significance Unknown.

            • glyburide

              protriptyline increases effects of glyburide by pharmacodynamic synergism. Minor/Significance Unknown.

            • hydroxyprogesterone caproate (DSC)

              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.

            • insulin aspart

              protriptyline increases effects of insulin aspart by pharmacodynamic synergism. Minor/Significance Unknown.

            • insulin detemir

              protriptyline increases effects of insulin detemir by pharmacodynamic synergism. Minor/Significance Unknown.

            • insulin glargine

              protriptyline increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.

            • insulin glulisine

              protriptyline increases effects of insulin glulisine by pharmacodynamic synergism. Minor/Significance Unknown.

            • insulin lispro

              protriptyline increases effects of insulin lispro by pharmacodynamic synergism. Minor/Significance Unknown.

            • insulin NPH

              protriptyline increases effects of insulin NPH by pharmacodynamic synergism. Minor/Significance Unknown.

            • insulin regular human

              protriptyline increases effects of insulin regular human by pharmacodynamic synergism. Minor/Significance Unknown.

            • isoproterenol

              isoproterenol, protriptyline. Mechanism: unknown. Minor/Significance Unknown. Risk of cardiac arrhythmias.

            • ketamine

              ketamine, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

            • lithium

              lithium, protriptyline. Other (see comment). Minor/Significance Unknown. Comment: Risk of neurotoxicity in geriatric pts. Multiple mechanisms involved.

            • mestranol

              mestranol, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • metformin

              protriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

            • miglitol

              protriptyline increases effects of miglitol by pharmacodynamic synergism. Minor/Significance Unknown.

            • nateglinide

              protriptyline increases effects of nateglinide by pharmacodynamic synergism. Minor/Significance Unknown.

            • panax ginseng

              panax ginseng increases effects of protriptyline by pharmacodynamic synergism. Minor/Significance Unknown.

            • pentobarbital

              pentobarbital, 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.

            • perphenazine

              protriptyline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              protriptyline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • phenobarbital

              phenobarbital, 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.

            • pioglitazone

              protriptyline increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

            • pleurisy root

              pleurisy root decreases effects of protriptyline by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.

            • primidone

              primidone, 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.

            • prochlorperazine

              protriptyline, prochlorperazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              protriptyline, prochlorperazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • progesterone micronized

              progesterone micronized, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

            • promazine

              protriptyline, promazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              protriptyline, promazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • promethazine

              protriptyline, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              protriptyline, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • propofol

              propofol, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

            • repaglinide

              protriptyline increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

            • rosiglitazone

              protriptyline increases effects of rosiglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

            • sage

              protriptyline and sage both increase sedation. Minor/Significance Unknown.

            • saxagliptin

              protriptyline increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

            • secobarbital

              secobarbital, 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.

            • serdexmethylphenidate/dexmethylphenidate

              serdexmethylphenidate/dexmethylphenidate increases effects of protriptyline by decreasing metabolism. Minor/Significance Unknown.

            • sevoflurane

              sevoflurane, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

            • sitagliptin

              protriptyline increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

            • sulfamethoxazole

              sulfamethoxazole decreases levels of protriptyline by unspecified interaction mechanism. Minor/Significance Unknown.

            • thioridazine

              protriptyline, thioridazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              protriptyline, thioridazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • tolazamide

              protriptyline increases effects of tolazamide by pharmacodynamic synergism. Minor/Significance Unknown.

            • tolbutamide

              protriptyline increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

            • trifluoperazine

              protriptyline, trifluoperazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.

              protriptyline, trifluoperazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • vasopressin

              protriptyline increases effects of vasopressin by pharmacodynamic synergism. Minor/Significance Unknown.

            • verapamil

              verapamil increases levels of protriptyline by decreasing metabolism. Minor/Significance Unknown.

            • vildagliptin

              protriptyline increases effects of vildagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

            • zolpidem

              zolpidem, protriptyline. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.

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            Adverse Effects

            1-10%

            Sedation

            Fatigue

            Headache

            Agitation

            Insomnia

            Blurred vision

            Weakness

            Lethargy

            Anxiety

            Dry mouth

            Constipation

            Nausea

            Vomiting

            Sweating

            Weight change

            Frequency Not Defined

            Confusion

            EPS

            Dizziness

            Tinnitus

            Paresthesia

            Seizure (rare)

            Worsening depression/suicide (rare)

            Orthostatic hypotension

            ECG changes

            Tachycardia

            Paralytic ileus (rare)

            Agranulocytosis (rare)

            Thrombocytopenia (rare)

            Eosinophilia (rare)

            Leukopenia (rare)

            Increased LFTs

            Sexual dysfunction

            Rash

            SIADH (rare)

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            Warnings

            Black Box Warnings

            In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 yr of age) taking antidepressants for major depressive disorders and other psychiatric illnesses

            This increase was not seen in patients aged >24 years; a slight decrease in suicidal thinking was seen in adults >65 years

            In children and young adults, risks must be weighed against the benefits of taking antidepressants

            Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during initial 1-2 months of therapy and dosage adjustments

            The patient’s family should communicate any abrupt changes in behavior to the healthcare provider

            Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy

            This drug is not approved for use in pediatric patients

            Contraindications

            Hypersensitivity

            Severe cardiovascular disorder

            Narrow angle glaucoma

            Within 14 days of MAOIs (risk of serotonin syndrome); if linezolid or IV methylene blue (MAOIs) must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity; may resume 24 hr after last linezolid or methylene blue dose, or after 2 weeks of monitoring, whichever comes first

            Any drugs or conditions that prolong QT interval

            Acute recovery post-MI

            Cautions

            Caution in BPH, urinary/GI retention, hyperthyroidism, open-angle glaucoma, seizure disorder, brain tumor, respiratory impairment

            Clinical worsening and suicide ideation may occur despite medication

            Risk of anticholinergic side-effects

            Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy

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            Pregnancy & Lactation

            Pregnancy Category: C

            Lactation: avoid

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Neurotransmitter (especially NE and serotonin) reuptake inhibitor; increases concentration of neurotransmitte in the central nervous system.

            Pharmacokinetics

            Half-Life: 54-92 hr

            Peak Plasma Time: 24-30 hr

            Protein binding: 92%

            Bioavailability: Completely absorbed

            Metabolism: Hepatic (oxidation, hydroxylation, glucuronidation)

            Excretion: Urine

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            protriptyline oral
            -
            5 mg tablet
            protriptyline oral
            -
            10 mg tablet
            protriptyline oral
            -
            5 mg tablet
            protriptyline oral
            -
            5 mg tablet
            protriptyline oral
            -
            10 mg tablet
            protriptyline oral
            -
            10 mg tablet

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Patient Education
            protriptyline oral

            PROTRIPTYLINE - ORAL

            (pro-TRIP-ti-leen)

            COMMON BRAND NAME(S): Vivactil

            WARNING: Antidepressant medications are used to treat a variety of conditions, including depression and other mental/mood disorders. These medications can help prevent suicidal thoughts/attempts and provide other important benefits. However, studies have shown that a small number of people (especially people younger than 25) who take antidepressants for any condition may experience worsening depression, other mental/mood symptoms, or suicidal thoughts/attempts. It is very important to talk with the doctor about the risks and benefits of antidepressant medication (especially for people younger than 25), even if treatment is not for a mental/mood condition. Tell the doctor right away if you notice worsening depression/other psychiatric conditions, unusual behavior changes (including possible suicidal thoughts/attempts), or other mental/mood changes (including new/worsening anxiety, panic attacks, trouble sleeping, irritability, hostile/angry feelings, impulsive actions, severe restlessness, very rapid speech). Be especially watchful for these symptoms when a new antidepressant is started or when the dose is changed.

            USES: This medication is used to treat mental/mood problems such as depression. It may help improve mood and feelings of well-being and increase your energy level. This medication belongs to a class of medications called tricyclic antidepressants. It works by affecting the balance of certain natural chemicals (neurotransmitters) in the brain.

            HOW TO USE: Read the Medication Guide provided by your pharmacist before you start taking protriptyline and each time you get a refill. If you have any questions, consult your doctor or pharmacist.Take this medication by mouth as directed by your doctor, usually 1 to 4 times daily. The dosage is based on your medical condition and response to treatment.To reduce your risk of side effects (such as dry mouth, anxiety, dizziness), your doctor may direct you to start this medication at a low dose and gradually increase your dose. Follow your doctor's instructions carefully.Take this medication regularly in order to get the most benefit from it. To help you remember, take it at the same time(s) each day. Do not increase your dose or use this drug more often or for longer than prescribed. Your condition will not improve any faster, and your risk of side effects will increase.Keep taking this medication even if you feel well. Do not stop taking this medication without consulting your doctor. Some conditions may become worse when this drug is suddenly stopped. Also, you may experience symptoms such as mood swings, headache, tiredness, and sleep change. To prevent these symptoms while you are stopping treatment with this drug, your doctor may reduce your dose gradually. Consult your doctor or pharmacist for more details. Report any new or worsening symptoms right away.This medication may not work right away. You may see some benefit within a week. However, it may take up to 4 weeks before you feel the full effect.Tell your doctor if your condition lasts or gets worse (such as your feelings of sadness get worse, or you have thoughts of suicide).

            SIDE EFFECTS: See also Warning section.Drowsiness, dizziness, dry mouth, blurred vision, constipation, weight gain, or trouble urinating may occur. If any of these effects last or get worse, notify your doctor or pharmacist promptly.To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.To relieve dry mouth, suck on (sugarless) hard candy or ice chips, chew (sugarless) gum, drink water, or use a saliva substitute.To prevent constipation, eat dietary fiber, drink enough water, and exercise. You may also need to take a laxative. Ask your pharmacist which type of laxative is right for you.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: heartburn that doesn't go away, mental/mood changes (such as anxiety, agitation, confusion), shaking, mask-like facial expressions, muscle spasms, severe stomach/abdominal pain, decreased sexual ability/desire, enlarged/painful breasts.Get medical help right away if you have any very serious side effects, including: slow/fast/irregular heartbeat, seizures, eye pain/swelling/redness, widened pupils, vision changes (such as seeing rainbows around lights at night).A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: See also Warning section.Before taking protriptyline, tell your doctor or pharmacist if you are allergic to it; or to other tricyclic antidepressants (such as nortriptyline); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: breathing problems, liver problems, heart problems (such as recent heart attack), problems urinating (such as due to enlarged prostate), overactive thyroid (hyperthyroidism), personal or family history of glaucoma (angle-closure type), personal or family history of mental/mood conditions (such as bipolar disorder, psychosis), family history of suicide, seizures, conditions that may increase your risk of seizures (such as other brain disease, alcohol withdrawal).This drug may make you dizzy or drowsy or blur your vision. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness or clear vision until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).This medication may make you more sensitive to the sun. Limit your time in the sun. Avoid tanning booths and sunlamps. Use sunscreen and wear protective clothing when outdoors. Tell your doctor right away if you get sunburned or have skin blisters/redness.If you have diabetes, this drug may make it harder to control your blood sugar levels. Monitor your blood sugar levels regularly and tell your doctor of the results. Your doctor may need to adjust your diabetes medication, exercise program, or diet.Older adults may be more sensitive to the side effects of this drug, especially dry mouth, dizziness, confusion, and difficulty urinating.During pregnancy, this medication should be used only when clearly needed. Since untreated mental/mood problems (such as depression) can be a serious condition, do not stop using this medication unless directed by your doctor. If you are planning pregnancy, become pregnant, or think you may be pregnant, immediately discuss with your doctor the benefits and risks of using this medication during pregnancy.It is unknown if this drug passes into breast milk, but it may have undesirable effects on a nursing infant. Consult your doctor before breast-feeding.

            DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: arbutamine, thyroid supplements, anticholinergic drugs (such as belladonna alkaloids), certain drugs for high blood pressure (drugs that work in the brain such as clonidine, guanabenz).Taking MAO inhibitors with this medication may cause a serious (possibly fatal) drug interaction. Avoid taking MAO inhibitors (isocarboxazid, linezolid, metaxalone, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, safinamide, selegiline, tranylcypromine) during treatment with this medication. Most MAO inhibitors should also not be taken for two weeks before and after treatment with this medication. Ask your doctor when to start or stop taking this medication.Other medications can affect the removal of protriptyline from your body, thereby affecting how protriptyline works. These drugs include cimetidine, drugs to treat irregular heart rate (such as quinidine/propafenone/flecainide), antidepressants (such as SSRIs including paroxetine/fluoxetine/fluvoxamine). This is not a complete list.Tell your doctor or pharmacist if you are taking other products that cause drowsiness, including alcohol, marijuana (cannabis), antihistamines (such as cetirizine, diphenhydramine), drugs for sleep or anxiety (such as alprazolam, diazepam, zolpidem), muscle relaxants, and opioid pain relievers (such as codeine).Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain decongestants or ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

            OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: extreme drowsiness, hallucinations, fast/irregular heartbeat, fainting, slow/shallow breathing, seizures.

            NOTES: Do not share this medication with others.Lab and/or medical tests (such as EKG, liver function) may be done while you are taking this medication. Keep all medical and lab appointments. Consult your doctor for more details.

            MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

            STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

            Information last revised March 2023. Copyright(c) 2023 First Databank, Inc.

            IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.