protriptyline (Rx)

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

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

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 (129)

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• sertraline

  sertraline and protriptyline both increase serotonin levels. 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.

• 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 (327)

• 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.

• 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.

• 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.

• 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.

• 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.

• 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

  protriptyline and cocaine 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.

• 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.

• 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.

• 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.

• gemifloxacin

  gemifloxacin 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• 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.

• thioridazine

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

• thiothixene

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

• 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.

• 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 (70)

• 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

  hydroxyprogesterone caproate, 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.

• 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.

• 5-HTP

  Monitor Closely (1)protriptyline and 5-HTP both increase serotonin levels. Modify Therapy/Monitor Closely.

• abiraterone

  Monitor Closely (1)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

  Monitor Closely (1)abobotulinumtoxinA increases effects of protriptyline by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects. .

• acarbose

  Minor (1)protriptyline increases effects of acarbose by pharmacodynamic synergism. Minor/Significance Unknown.

• aclidinium

  Monitor Closely (1)aclidinium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• albuterol

  Monitor Closely (2)albuterol and protriptyline both increase QTc interval. Use Caution/Monitor.
  
  protriptyline increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, albuterol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• alfentanil

  Monitor Closely (1)alfentanil and protriptyline both increase sedation. Use Caution/Monitor.

• alfuzosin

  Monitor Closely (2)protriptyline and alfuzosin both increase QTc interval. Use Caution/Monitor.
  
  alfuzosin and protriptyline both increase QTc interval. Use Caution/Monitor.

• almotriptan

  Monitor Closely (1)almotriptan and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• alprazolam

  Monitor Closely (1)alprazolam and protriptyline both increase sedation. Use Caution/Monitor.

• amifampridine

  Monitor Closely (1)protriptyline increases toxicity of amifampridine by Other (see comment). Modify Therapy/Monitor Closely. Comment: Amifampridine can cause seizures. Coadministration with drugs that lower seizure threshold may increase this risk.

• amiodarone

  Serious - Use Alternative (1)protriptyline and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.

• amisulpride

  Monitor Closely (1)protriptyline and amisulpride both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended if coadministered.

• amitriptyline

  Monitor Closely (2)amitriptyline and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  amitriptyline and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)amitriptyline and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• amobarbital

  Monitor Closely (1)amobarbital and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)amobarbital, protriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• amoxapine

  Monitor Closely (2)amoxapine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  amoxapine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)amoxapine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  amoxapine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• anticholinergic/sedative combos

  Monitor Closely (1)anticholinergic/sedative combos and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• apomorphine

  Monitor Closely (1)protriptyline and apomorphine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)apomorphine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• arformoterol

  Monitor Closely (2)arformoterol and protriptyline both increase QTc interval. Use Caution/Monitor.
  
  protriptyline increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, arformoterol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• aripiprazole

  Monitor Closely (1)aripiprazole and protriptyline both increase sedation. Use Caution/Monitor.

• armodafinil

  Monitor Closely (1)protriptyline increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• arsenic trioxide

  Serious - Use Alternative (1)protriptyline and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.

• artemether

  Serious - Use Alternative (1)artemether and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• artemether/lumefantrine

  Serious - Use Alternative (1)protriptyline and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

• atazanavir

  Monitor Closely (1)atazanavir increases levels of protriptyline by unspecified interaction mechanism. Use Caution/Monitor.

• atomoxetine

  Monitor Closely (1)atomoxetine and protriptyline both increase QTc interval. Use Caution/Monitor.

• atracurium

  Monitor Closely (1)atracurium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• atropine

  Monitor Closely (1)atropine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)protriptyline increases levels of atropine by unknown mechanism. Minor/Significance Unknown.

• atropine IV/IM

  Monitor Closely (1)atropine IV/IM and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.Minor (1)protriptyline increases levels of atropine IV/IM by unknown mechanism. Minor/Significance Unknown.

• azelastine

  Monitor Closely (1)azelastine and protriptyline both increase sedation. Use Caution/Monitor.

• azithromycin

  Monitor Closely (1)protriptyline and azithromycin both increase QTc interval. Use Caution/Monitor.

• baclofen

  Monitor Closely (1)baclofen and protriptyline both increase sedation. Use Caution/Monitor.

• bazedoxifene/conjugated estrogens

  Minor (1)bazedoxifene/conjugated estrogens, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• bedaquiline

  Monitor Closely (1)protriptyline and bedaquiline both increase QTc interval. Modify Therapy/Monitor Closely. ECG should be monitored closely

• belladonna alkaloids

  Monitor Closely (1)belladonna alkaloids and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• belladonna and opium

  Monitor Closely (2)belladonna and opium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  belladonna and opium and protriptyline both increase sedation. Use Caution/Monitor.

• benperidol

  Monitor Closely (1)benperidol and protriptyline both increase sedation. Use Caution/Monitor.

• benzhydrocodone/acetaminophen

  Monitor Closely (1)benzhydrocodone/acetaminophen, protriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

• benzphetamine

  Monitor Closely (1)protriptyline increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, benzphetamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• benztropine

  Monitor Closely (1)benztropine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• bethanechol

  Monitor Closely (1)bethanechol increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• brimonidine

  Minor (1)protriptyline decreases effects of brimonidine by pharmacodynamic antagonism. Minor/Significance Unknown.

• brompheniramine

  Monitor Closely (1)brompheniramine and protriptyline both increase sedation. Use Caution/Monitor.

• buprenorphine

  Monitor Closely (1)buprenorphine and protriptyline both increase sedation. Use Caution/Monitor.

• buprenorphine buccal

  Monitor Closely (1)buprenorphine buccal and protriptyline both increase sedation. Use Caution/Monitor.

• buprenorphine subdermal implant

  Monitor Closely (1)protriptyline, buprenorphine subdermal implant. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

• buprenorphine, long-acting injection

  Monitor Closely (1)protriptyline, buprenorphine, long-acting injection. Either increases toxicity of the other by serotonin levels. Use Caution/Monitor. Concomitant use could result in life-threatening serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation, and during dose adjustment of the serotonergic drug. Discontinue buprenorphine if serotonin syndrome is suspected.

• bupropion

  Monitor Closely (2)protriptyline increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.
  
  bupropion will increase the level or effect of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• buspirone

  Serious - Use Alternative (1)protriptyline and buspirone both increase serotonin levels. Avoid or Use Alternate Drug.

• butabarbital

  Monitor Closely (1)butabarbital and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)butabarbital, protriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• butalbital

  Monitor Closely (1)butalbital and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)butalbital, protriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• butorphanol

  Monitor Closely (1)butorphanol and protriptyline both increase sedation. Use Caution/Monitor.

• caffeine

  Monitor Closely (1)protriptyline increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• calcium/magnesium/potassium/sodium oxybates

  Serious - Use Alternative (1)protriptyline, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

• carbachol

  Monitor Closely (1)carbachol increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• carbamazepine

  Minor (1)carbamazepine decreases levels of protriptyline by increasing metabolism. Minor/Significance Unknown.

• carbinoxamine

  Monitor Closely (1)carbinoxamine and protriptyline both increase sedation. Use Caution/Monitor.

• carisoprodol

  Monitor Closely (1)carisoprodol and protriptyline both increase sedation. Use Caution/Monitor.

• cenobamate

  Monitor Closely (1)cenobamate, protriptyline. Either increases effects of the other by sedation. Use Caution/Monitor.

• ceritinib

  Monitor Closely (1)ceritinib and protriptyline both increase QTc interval. Use Caution/Monitor.

• cevimeline

  Monitor Closely (1)cevimeline increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• chloral hydrate

  Monitor Closely (1)chloral hydrate and protriptyline both increase sedation. Use Caution/Monitor.

• chlordiazepoxide

  Monitor Closely (1)chlordiazepoxide and protriptyline both increase sedation. Use Caution/Monitor.

• chloroquine

  Minor (1)chloroquine increases toxicity of protriptyline by QTc interval. Minor/Significance Unknown.

• chlorpheniramine

  Monitor Closely (1)chlorpheniramine and protriptyline both increase sedation. Use Caution/Monitor.

• chlorpromazine

  Monitor Closely (1)chlorpromazine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)chlorpromazine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)protriptyline, chlorpromazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  protriptyline, chlorpromazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• chlorpropamide

  Minor (1)protriptyline increases effects of chlorpropamide by pharmacodynamic synergism. Minor/Significance Unknown.

• chlorzoxazone

  Monitor Closely (1)chlorzoxazone and protriptyline both increase sedation. Use Caution/Monitor.

• cinnarizine

  Monitor Closely (1)cinnarizine and protriptyline both increase sedation. Use Caution/Monitor.

• cisatracurium

  Monitor Closely (1)cisatracurium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• citalopram

  Serious - Use Alternative (2)citalopram and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Citalopram may increase TCA levels. Increased risk of serotonin syndrome or neuroleptic malignant syndrome. Potential risk for QT prolongation. ECG monitoring is recommended.
  
  citalopram and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• clarithromycin

  Serious - Use Alternative (1)protriptyline and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug.

• clemastine

  Monitor Closely (1)clemastine and protriptyline both increase sedation. Use Caution/Monitor.

• clobazam

  Monitor Closely (2)clobazam will increase the level or effect of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly.
  
  protriptyline, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

• clomipramine

  Monitor Closely (2)clomipramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  clomipramine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)clomipramine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  clomipramine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• clonazepam

  Monitor Closely (1)clonazepam and protriptyline both increase sedation. Use Caution/Monitor.

• clonidine

  Serious - Use Alternative (1)protriptyline decreases effects of clonidine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• clorazepate

  Monitor Closely (1)clorazepate and protriptyline both increase sedation. Use Caution/Monitor.

• clozapine

  Monitor Closely (2)clozapine and protriptyline both increase QTc interval. Use Caution/Monitor.
  
  clozapine and protriptyline both increase sedation. Use Caution/Monitor.

• cobicistat

  Monitor Closely (1)cobicistat will increase the level or effect of protriptyline by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.

• cocaine

  Monitor Closely (1)protriptyline and cocaine both increase serotonin levels. Modify Therapy/Monitor Closely.

• codeine

  Monitor Closely (1)codeine and protriptyline both increase sedation. Use Caution/Monitor.

• conjugated estrogens

  Minor (1)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

  Minor (1)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.

• crizotinib

  Monitor Closely (1)crizotinib and protriptyline both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended, along with drugs that may prolong the QT interval.

• cyclizine

  Monitor Closely (2)cyclizine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  cyclizine and protriptyline both increase sedation. Use Caution/Monitor.

• cyclobenzaprine

  Monitor Closely (2)cyclobenzaprine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  cyclobenzaprine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline and cyclobenzaprine both increase serotonin levels. Avoid or Use Alternate Drug.

• cyproheptadine

  Monitor Closely (1)cyproheptadine and protriptyline both increase sedation. Use Caution/Monitor.

• dacomitinib

  Serious - Use Alternative (1)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.

• dantrolene

  Monitor Closely (1)dantrolene and protriptyline both increase sedation. Use Caution/Monitor.

• daridorexant

  Monitor Closely (1)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

  Monitor Closely (1)darifenacin and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• dasatinib

  Monitor Closely (1)protriptyline and dasatinib both increase QTc interval. Modify Therapy/Monitor Closely.

• debrisoquine

  Monitor Closely (1)protriptyline decreases effects of debrisoquine by Other (see comment). Use Caution/Monitor. Comment: Inhibition of uptake by adrenergic neurons.

• degarelix

  Monitor Closely (1)degarelix and protriptyline both increase QTc interval. Use Caution/Monitor.

• desflurane

  Monitor Closely (2)desflurane and protriptyline both increase QTc interval. Use Caution/Monitor.
  
  desflurane and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)desflurane, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• desipramine

  Monitor Closely (2)desipramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  desipramine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)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

  Serious - Use Alternative (1)protriptyline and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

• deutetrabenazine

  Monitor Closely (2)protriptyline and deutetrabenazine both increase sedation. Use Caution/Monitor.
  
  deutetrabenazine and protriptyline both increase QTc interval. Use Caution/Monitor.

• dexchlorpheniramine

  Monitor Closely (1)dexchlorpheniramine and protriptyline both increase sedation. Use Caution/Monitor.

• dexfenfluramine

  Monitor Closely (2)protriptyline and dexfenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  protriptyline increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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.

• dexmedetomidine

  Monitor Closely (1)dexmedetomidine and protriptyline both increase sedation. Use Caution/Monitor.

• dexmethylphenidate

  Monitor Closely (1)protriptyline increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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.Minor (1)dexmethylphenidate increases effects of protriptyline by decreasing metabolism. Minor/Significance Unknown.

• dextroamphetamine

  Monitor Closely (3)protriptyline increases effects of dextroamphetamine by unknown mechanism. Use Caution/Monitor.
  
  protriptyline and dextroamphetamine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  protriptyline increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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

  Serious - Use Alternative (1)protriptyline and dextromethorphan both increase serotonin levels. Avoid or Use Alternate Drug.

• dextromoramide

  Monitor Closely (1)dextromoramide and protriptyline both increase sedation. Use Caution/Monitor.

• diamorphine

  Monitor Closely (1)diamorphine and protriptyline both increase sedation. Use Caution/Monitor.

• diazepam

  Monitor Closely (1)diazepam and protriptyline both increase sedation. Use Caution/Monitor.

• diazepam intranasal

  Monitor Closely (1)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

  Monitor Closely (1)dicyclomine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• diethylpropion

  Monitor Closely (1)protriptyline increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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.

• difelikefalin

  Monitor Closely (1)difelikefalin and protriptyline both increase sedation. Use Caution/Monitor.

• difenoxin hcl

  Monitor Closely (1)difenoxin hcl and protriptyline both increase sedation. Use Caution/Monitor.

• dihydroergotamine

  Monitor Closely (1)protriptyline and dihydroergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• dihydroergotamine intranasal

  Monitor Closely (1)protriptyline and dihydroergotamine intranasal both increase serotonin levels. Modify Therapy/Monitor Closely.

• dimenhydrinate

  Monitor Closely (1)dimenhydrinate and protriptyline both increase sedation. Use Caution/Monitor.

• diphenhydramine

  Monitor Closely (2)diphenhydramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and protriptyline both increase sedation. Use Caution/Monitor.

• diphenoxylate hcl

  Monitor Closely (1)diphenoxylate hcl and protriptyline both increase sedation. Use Caution/Monitor.

• dipipanone

  Monitor Closely (1)dipipanone and protriptyline both increase sedation. Use Caution/Monitor.

• disopyramide

  Contraindicated (1)protriptyline and disopyramide both increase QTc interval. Contraindicated.

• dobutamine

  Monitor Closely (1)protriptyline increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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

  Monitor Closely (1)dofetilide increases toxicity of protriptyline by QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.

• dolasetron

  Monitor Closely (1)protriptyline and dolasetron both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)dolasetron, protriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• donepezil

  Monitor Closely (2)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

  Monitor Closely (1)protriptyline increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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

  Monitor Closely (1)protriptyline increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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

  Monitor Closely (2)doxepin and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  doxepin and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)doxepin and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  doxepin and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• doxylamine

  Monitor Closely (1)doxylamine and protriptyline both increase sedation. Use Caution/Monitor.

• dronedarone

  Serious - Use Alternative (1)protriptyline and dronedarone both increase QTc interval. Avoid or Use Alternate Drug.

• droperidol

  Monitor Closely (1)droperidol and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline and droperidol both increase QTc interval. Avoid or Use Alternate Drug.

• duloxetine

  Serious - Use Alternative (1)duloxetine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• echothiophate iodide

  Monitor Closely (1)echothiophate iodide increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• efavirenz

  Monitor Closely (1)efavirenz and protriptyline both increase QTc interval. Use Caution/Monitor.

• eletriptan

  Monitor Closely (1)eletriptan and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• eliglustat

  Monitor Closely (1)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.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (1)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.

• encorafenib

  Serious - Use Alternative (1)encorafenib and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• entrectinib

  Monitor Closely (1)entrectinib and protriptyline both increase QTc interval. Use Caution/Monitor.

• ephedrine

  Monitor Closely (2)protriptyline increases effects of ephedrine by unknown mechanism. Use Caution/Monitor.
  
  protriptyline increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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

  Monitor Closely (2)protriptyline increases effects of epinephrine by unknown mechanism. Use Caution/Monitor.
  
  protriptyline increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (2)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 inhaled

  Monitor Closely (1)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

  Monitor Closely (2)protriptyline increases effects of epinephrine racemic by unknown mechanism. Use Caution/Monitor.
  
  protriptyline increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (2)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.

• ergotamine

  Monitor Closely (1)protriptyline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• eribulin

  Monitor Closely (1)eribulin and protriptyline both increase QTc interval. Use Caution/Monitor.

• erythromycin base

  Serious - Use Alternative (1)protriptyline and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  Serious - Use Alternative (1)protriptyline and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  Serious - Use Alternative (1)protriptyline and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin stearate

  Serious - Use Alternative (1)protriptyline and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.

• escitalopram

  Monitor Closely (1)escitalopram increases toxicity of protriptyline by QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)escitalopram and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• esketamine intranasal

  Monitor Closely (1)esketamine intranasal, protriptyline. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

• estazolam

  Monitor Closely (1)estazolam and protriptyline both increase sedation. Use Caution/Monitor.

• estradiol

  Minor (1)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

  Minor (1)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

  Minor (1)estrogens esterified, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens may inhibit hepatic metabolism of tricyclic antidepressants. However, interactions are not common.

• estropipate

  Minor (1)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.

• ethanol

  Monitor Closely (1)protriptyline and ethanol both increase sedation. Use Caution/Monitor.

• ethinylestradiol

  Minor (1)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

  Monitor Closely (1)etomidate and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)etomidate, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• eucalyptus

  Minor (1)protriptyline and eucalyptus both increase sedation. Minor/Significance Unknown.

• ezogabine

  Monitor Closely (1)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

  Monitor Closely (1)fedratinib will increase the level or effect of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

• fenfluramine

  Monitor Closely (3)fenfluramine, protriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration with drugs that increase serotoninergic effects may increase the risk of serotonin syndrome.
  
  protriptyline and fenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  protriptyline increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, fenfluramine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• fesoterodine

  Monitor Closely (1)fesoterodine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• fexinidazole

  Serious - Use Alternative (1)fexinidazole and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.

• fingolimod

  Monitor Closely (1)fingolimod and protriptyline both increase QTc interval. Use Caution/Monitor.

• flavoxate

  Monitor Closely (1)flavoxate and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• flecainide

  Monitor Closely (1)protriptyline and flecainide both increase QTc interval. Modify Therapy/Monitor Closely.

• fluconazole

  Serious - Use Alternative (1)protriptyline and fluconazole both increase QTc interval. Avoid or Use Alternate Drug.

• fluoxetine

  Monitor Closely (1)protriptyline and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)fluoxetine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• fluphenazine

  Monitor Closely (1)fluphenazine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)fluphenazine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)protriptyline, fluphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  protriptyline, fluphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• flurazepam

  Monitor Closely (1)flurazepam and protriptyline both increase sedation. Use Caution/Monitor.

• fluvoxamine

  Monitor Closely (1)fluvoxamine and protriptyline both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)fluvoxamine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• formoterol

  Monitor Closely (1)protriptyline increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (2)protriptyline and formoterol both increase QTc interval. Avoid or Use Alternate Drug.
  
  protriptyline, formoterol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• fosamprenavir

  Serious - Use Alternative (1)fosamprenavir increases levels of protriptyline by decreasing metabolism. Avoid or Use Alternate Drug.

• foscarnet

  Monitor Closely (1)protriptyline and foscarnet both increase QTc interval. Modify Therapy/Monitor Closely.

• frovatriptan

  Monitor Closely (1)frovatriptan and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• gabapentin

  Monitor Closely (1)gabapentin, protriptyline. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• gabapentin enacarbil

  Monitor Closely (1)gabapentin enacarbil, protriptyline. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of CNS depressants can result in serious, life-threatening, and fatal respiratory depression. Use lowest dose possible and monitor for respiratory depression and sedation.

• galantamine

  Monitor Closely (1)galantamine increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• gemifloxacin

  Monitor Closely (1)gemifloxacin and protriptyline both increase QTc interval. Use Caution/Monitor.

• givosiran

  Serious - Use Alternative (1)givosiran will increase the level or effect of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP2D6 substrates with givosiran. If unavoidable, decrease the CYP2D6 substrate dosage in accordance with approved product labeling.

• glimepiride

  Minor (1)protriptyline increases effects of glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.

• glipizide

  Minor (1)protriptyline increases effects of glipizide by pharmacodynamic synergism. Minor/Significance Unknown.

• glyburide

  Minor (1)protriptyline increases effects of glyburide by pharmacodynamic synergism. Minor/Significance Unknown.

• glycopyrrolate

  Monitor Closely (2)glycopyrrolate and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  protriptyline increases levels of glycopyrrolate by unknown mechanism. Use Caution/Monitor.

• glycopyrrolate inhaled

  Monitor Closely (2)glycopyrrolate inhaled and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  protriptyline increases levels of glycopyrrolate inhaled by unknown mechanism. Use Caution/Monitor.

• glycopyrronium tosylate topical

  Monitor Closely (1)glycopyrronium tosylate topical, protriptyline. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of glycopyrronium tosylate topical with other anticholinergic medications may result in additive anticholinergic adverse effects.

• granisetron

  Serious - Use Alternative (1)granisetron, protriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• guanfacine

  Serious - Use Alternative (1)protriptyline decreases effects of guanfacine by Other (see comment). Avoid or Use Alternate Drug. Comment: Inhibition of uptake by adrenergic neurons.

• haloperidol

  Monitor Closely (1)haloperidol and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline and haloperidol both increase QTc interval. Avoid or Use Alternate Drug.

• henbane

  Monitor Closely (1)henbane and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• homatropine

  Monitor Closely (1)homatropine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• huperzine A

  Monitor Closely (1)huperzine A increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• hydrocodone

  Monitor Closely (1)hydrocodone, protriptyline. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Coadministration of drugs that affect the serotonergic neurotransmitter system may result in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.

• hydromorphone

  Monitor Closely (1)hydromorphone and protriptyline both increase sedation. Use Caution/Monitor.

• hydroxychloroquine sulfate

  Serious - Use Alternative (1)hydroxychloroquine sulfate and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• hydroxyprogesterone caproate

  Minor (1)hydroxyprogesterone caproate, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Estrogens and progestins may decr tricyclic antidepressant effects, while increasing TCA plasma concentration and adverse effects.

• hydroxyzine

  Monitor Closely (1)hydroxyzine and protriptyline both increase sedation. Use Caution/Monitor.

• hyoscyamine

  Monitor Closely (1)hyoscyamine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• hyoscyamine spray

  Monitor Closely (1)hyoscyamine spray and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• ibutilide

  Contraindicated (1)protriptyline and ibutilide both increase QTc interval. Contraindicated.

• iloperidone

  Monitor Closely (2)protriptyline and iloperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  iloperidone and protriptyline both increase sedation. Use Caution/Monitor.

• imipramine

  Monitor Closely (2)imipramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  imipramine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)imipramine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  imipramine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• indacaterol, inhaled

  Monitor Closely (1)indacaterol, inhaled, protriptyline. QTc interval. Use Caution/Monitor. Indacaterol should be administered with extreme caution to patients treated with TCAs. Drugs that are known to prolong the QTc interval may have an increased the risk of ventricular arrhythmias.

• indapamide

  Contraindicated (1)protriptyline and indapamide both increase QTc interval. Contraindicated.

• insulin aspart

  Minor (1)protriptyline increases effects of insulin aspart by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin detemir

  Minor (1)protriptyline increases effects of insulin detemir by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin glargine

  Minor (1)protriptyline increases effects of insulin glargine by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin glulisine

  Minor (1)protriptyline increases effects of insulin glulisine by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin lispro

  Minor (1)protriptyline increases effects of insulin lispro by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin NPH

  Minor (1)protriptyline increases effects of insulin NPH by pharmacodynamic synergism. Minor/Significance Unknown.

• insulin regular human

  Minor (1)protriptyline increases effects of insulin regular human by pharmacodynamic synergism. Minor/Significance Unknown.

• iobenguane I 123

  Contraindicated (1)protriptyline decreases effects of iobenguane I 123 by pharmacodynamic antagonism. Contraindicated. If clinically appropriate, discontinue drugs that decrease uptake of NE for at least 5 half-lives; may cause false-negative imaging results.

• iobenguane I 131

  Serious - Use Alternative (1)protriptyline will decrease the level or effect of iobenguane I 131 by Other (see comment). Avoid or Use Alternate Drug. Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells, and thus, reduce iobenguane efficacy. Discontinue interfering drugs for at least 5 half-lives before administration of either the dosimetry or an iobenguane dose. Do not administer these drugs until at least 7 days after each iobenguane dose.

• ipratropium

  Monitor Closely (1)ipratropium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• isocarboxazid

  Contraindicated (1)isocarboxazid and protriptyline both increase serotonin levels. Contraindicated.

• isoniazid

  Monitor Closely (1)protriptyline and isoniazid both increase serotonin levels. Modify Therapy/Monitor Closely.

• isoproterenol

  Monitor Closely (1)protriptyline increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, isoproterenol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.Minor (1)isoproterenol, protriptyline. Mechanism: unknown. Minor/Significance Unknown. Risk of cardiac arrhythmias.

• itraconazole

  Serious - Use Alternative (1)protriptyline and itraconazole both increase QTc interval. Avoid or Use Alternate Drug.

• ivosidenib

  Serious - Use Alternative (1)ivosidenib and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of QTc prolonging drugs with ivosidenib or replace with alternate therapies. If coadministration of a QTc prolonging drug is unavoidable, monitor for increased risk of QTc interval prolongation.

• ketamine

  Monitor Closely (1)ketamine and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)ketamine, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• ketoconazole

  Serious - Use Alternative (1)protriptyline and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• ketotifen, ophthalmic

  Monitor Closely (1)protriptyline and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

• L-tryptophan

  Monitor Closely (1)protriptyline and L-tryptophan both increase serotonin levels. Modify Therapy/Monitor Closely.

• lapatinib

  Monitor Closely (1)protriptyline and lapatinib both increase QTc interval. Modify Therapy/Monitor Closely.

• lasmiditan

  Monitor Closely (2)lasmiditan, protriptyline. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.
  
  protriptyline increases effects of lasmiditan by serotonin levels. Use Caution/Monitor. Coadministration may increase risk of serotonin syndrome.

• lemborexant

  Monitor Closely (1)lemborexant, protriptyline. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

• levalbuterol

  Monitor Closely (1)protriptyline increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, levalbuterol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• levofloxacin

  Monitor Closely (1)protriptyline and levofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

• levomilnacipran

  Serious - Use Alternative (1)levomilnacipran and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• levorphanol

  Monitor Closely (1)levorphanol and protriptyline both increase sedation. Use Caution/Monitor.

• linezolid

  Serious - Use Alternative (1)linezolid and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug. Linezolid may increase serotonin as a result of MAO-A inhibition. If linezolid must be administered, discontinue serotonergic drug immediately and monitor for CNS toxicity. Serotonergic therapy may be resumed 24 hours after last linezolid dose or after 2 weeks of monitoring, whichever comes first.

• lisdexamfetamine

  Monitor Closely (2)protriptyline, lisdexamfetamine. Either increases effects of the other by serotonin levels. Use Caution/Monitor. Initiate with lower doses and monitor for signs and symptoms of serotonin syndrome, particularly during initiation or dosage increase. If serotonin syndrome occurs, discontinue along with concomitant serotonergic drug(s).
  
  protriptyline increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline, lisdexamfetamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• lithium

  Monitor Closely (1)protriptyline and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)lithium, protriptyline. Other (see comment). Minor/Significance Unknown. Comment: Risk of neurotoxicity in geriatric pts. Multiple mechanisms involved.

• lofepramine

  Monitor Closely (2)lofepramine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  lofepramine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)lofepramine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  lofepramine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• lofexidine

  Monitor Closely (2)protriptyline decreases effects of lofexidine by unspecified interaction mechanism. Use Caution/Monitor.
  
  protriptyline and lofexidine both increase sedation. Use Caution/Monitor.

• loprazolam

  Monitor Closely (1)loprazolam and protriptyline both increase sedation. Use Caution/Monitor.

• lorazepam

  Monitor Closely (1)lorazepam and protriptyline both increase sedation. Use Caution/Monitor.

• lorcaserin

  Monitor Closely (1)lorcaserin will increase the level or effect of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline and lorcaserin both increase serotonin levels. Avoid or Use Alternate Drug.

• lormetazepam

  Monitor Closely (1)lormetazepam and protriptyline both increase sedation. Use Caution/Monitor.

• loxapine

  Monitor Closely (1)loxapine and protriptyline both increase sedation. Use Caution/Monitor.

• loxapine inhaled

  Monitor Closely (1)loxapine inhaled and protriptyline both increase sedation. Use Caution/Monitor.

• lsd

  Monitor Closely (1)protriptyline and lsd both increase serotonin levels. Modify Therapy/Monitor Closely.

• lumefantrine

  Serious - Use Alternative (1)protriptyline and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

• lurasidone

  Monitor Closely (1)lurasidone, protriptyline. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for additive CNS effects .

• macimorelin

  Serious - Use Alternative (1)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

  Monitor Closely (2)maprotiline and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  maprotiline and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)maprotiline and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  maprotiline and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• marijuana

  Monitor Closely (1)protriptyline and marijuana both increase sedation. Use Caution/Monitor.

• meclizine

  Monitor Closely (1)meclizine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• mefloquine

  Serious - Use Alternative (1)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.

• melatonin

  Monitor Closely (1)protriptyline and melatonin both increase sedation. Use Caution/Monitor.

• meperidine

  Monitor Closely (1)meperidine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline and meperidine both increase serotonin levels. Avoid or Use Alternate Drug.

• meprobamate

  Monitor Closely (1)protriptyline and meprobamate both increase sedation. Use Caution/Monitor.

• mestranol

  Minor (1)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.

• metaproterenol

  Monitor Closely (1)protriptyline increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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.

• metaxalone

  Monitor Closely (1)metaxalone and protriptyline both increase sedation. Use Caution/Monitor.

• metformin

  Minor (1)protriptyline increases effects of metformin by pharmacodynamic synergism. Minor/Significance Unknown.

• methadone

  Monitor Closely (2)protriptyline and methadone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  methadone and protriptyline both increase sedation. Use Caution/Monitor.

• methamphetamine

  Monitor Closely (1)protriptyline increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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.

• methocarbamol

  Monitor Closely (1)methocarbamol and protriptyline both increase sedation. Use Caution/Monitor.

• methscopolamine

  Monitor Closely (1)methscopolamine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• methylene blue

  Serious - Use Alternative (1)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

  Monitor Closely (1)protriptyline increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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.

• methylphenidate

  Monitor Closely (1)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.

• metoclopramide intranasal

  Serious - Use Alternative (1)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.

• midazolam

  Monitor Closely (1)midazolam and protriptyline both increase sedation. Use Caution/Monitor.

• midodrine

  Monitor Closely (1)protriptyline increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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.

• mifepristone

  Monitor Closely (1)mifepristone, protriptyline. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.

• miglitol

  Minor (1)protriptyline increases effects of miglitol by pharmacodynamic synergism. Minor/Significance Unknown.

• milnacipran

  Serious - Use Alternative (1)milnacipran and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• mirabegron

  Monitor Closely (1)mirabegron will increase the level or effect of protriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

• mirtazapine

  Monitor Closely (2)protriptyline and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  protriptyline and mirtazapine both increase sedation. Use Caution/Monitor.

• mobocertinib

  Serious - Use Alternative (1)mobocertinib and protriptyline both increase QTc interval. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently.

• modafinil

  Monitor Closely (1)protriptyline increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• morphine

  Monitor Closely (2)protriptyline and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  morphine and protriptyline both increase sedation. Use Caution/Monitor.

• motherwort

  Monitor Closely (1)protriptyline and motherwort both increase sedation. Use Caution/Monitor.

• moxifloxacin

  Serious - Use Alternative (1)protriptyline and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.

• moxonidine

  Monitor Closely (1)protriptyline and moxonidine both increase sedation. Use Caution/Monitor.

• nabilone

  Monitor Closely (1)protriptyline and nabilone both increase sedation. Use Caution/Monitor.

• nalbuphine

  Monitor Closely (1)nalbuphine and protriptyline both increase sedation. Use Caution/Monitor.

• naratriptan

  Monitor Closely (1)naratriptan and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• nateglinide

  Minor (1)protriptyline increases effects of nateglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• nefazodone

  Serious - Use Alternative (1)nefazodone and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• nefopam

  Monitor Closely (1)nefopam, protriptyline. Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Use combination with caution.

• neostigmine

  Monitor Closely (1)neostigmine increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• netupitant/palonosetron

  Serious - Use Alternative (1)netupitant/palonosetron, protriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• nilotinib

  Serious - Use Alternative (1)protriptyline and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.

• norepinephrine

  Monitor Closely (2)protriptyline increases effects of norepinephrine by unknown mechanism. Use Caution/Monitor.
  
  protriptyline increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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

  Monitor Closely (2)nortriptyline and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  nortriptyline and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)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

  Serious - Use Alternative (1)protriptyline and octreotide both increase QTc interval. Avoid or Use Alternate Drug.

• octreotide (Antidote)

  Serious - Use Alternative (1)protriptyline and octreotide (Antidote) both increase QTc interval. Avoid or Use Alternate Drug.

• ofloxacin

  Monitor Closely (1)protriptyline and ofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

• olanzapine

  Monitor Closely (1)olanzapine and protriptyline both increase sedation. Use Caution/Monitor.

• oliceridine

  Monitor Closely (2)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

  Monitor Closely (1)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

  Monitor Closely (1)onabotulinumtoxinA and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• ondansetron

  Serious - Use Alternative (2)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.

• opium tincture

  Monitor Closely (1)opium tincture and protriptyline both increase sedation. Use Caution/Monitor.

• orphenadrine

  Monitor Closely (2)protriptyline and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  orphenadrine and protriptyline both increase sedation. Use Caution/Monitor.

• osimertinib

  Monitor Closely (1)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

  Monitor Closely (1)oxazepam and protriptyline both increase sedation. Use Caution/Monitor.

• oxybutynin

  Monitor Closely (1)oxybutynin and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• oxybutynin topical

  Monitor Closely (1)oxybutynin topical and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• oxybutynin transdermal

  Monitor Closely (1)oxybutynin transdermal and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• oxycodone

  Monitor Closely (1)oxycodone and protriptyline both increase sedation. Use Caution/Monitor.

• oxymetazoline intranasal

  Monitor Closely (1)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

  Monitor Closely (1)oxymorphone and protriptyline both increase sedation. Use Caution/Monitor.

• ozanimod

  Monitor Closely (1)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.Serious - Use Alternative (1)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.

• paliperidone

  Monitor Closely (2)protriptyline and paliperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  paliperidone and protriptyline both increase sedation. Use Caution/Monitor.

• palonosetron

  Serious - Use Alternative (1)palonosetron, protriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• panax ginseng

  Minor (1)panax ginseng increases effects of protriptyline by pharmacodynamic synergism. Minor/Significance Unknown.

• pancuronium

  Monitor Closely (1)pancuronium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• papaveretum

  Monitor Closely (1)papaveretum and protriptyline both increase sedation. Use Caution/Monitor.

• papaverine

  Monitor Closely (1)protriptyline and papaverine both increase sedation. Use Caution/Monitor.

• paroxetine

  Monitor Closely (1)protriptyline and paroxetine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)paroxetine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• pasireotide

  Monitor Closely (1)protriptyline and pasireotide both increase QTc interval. Modify Therapy/Monitor Closely.

• pazopanib

  Monitor Closely (1)protriptyline and pazopanib both increase QTc interval. Use Caution/Monitor.

• peginterferon alfa 2b

  Monitor Closely (1)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.

• pentamidine

  Contraindicated (1)protriptyline and pentamidine both increase QTc interval. Contraindicated.

• pentazocine

  Monitor Closely (2)protriptyline and pentazocine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  pentazocine and protriptyline both increase sedation. Use Caution/Monitor.

• pentobarbital

  Monitor Closely (1)pentobarbital and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)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

  Monitor Closely (1)perphenazine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)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.

• phendimetrazine

  Monitor Closely (1)protriptyline increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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.

• phenelzine

  Contraindicated (1)phenelzine and protriptyline both increase serotonin levels. Contraindicated.

• phenobarbital

  Monitor Closely (1)phenobarbital and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)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.

• phentermine

  Monitor Closely (1)protriptyline increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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

  Monitor Closely (1)protriptyline increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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 ophthalmic

  Monitor Closely (1)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

  Monitor Closely (1)protriptyline increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .Serious - Use Alternative (1)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.

• pholcodine

  Monitor Closely (1)protriptyline and pholcodine both increase sedation. Use Caution/Monitor.

• physostigmine

  Monitor Closely (1)physostigmine increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pilocarpine

  Monitor Closely (1)pilocarpine increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• pimozide

  Contraindicated (1)protriptyline and pimozide both increase QTc interval. Contraindicated.Monitor Closely (1)pimozide and protriptyline both increase sedation. Use Caution/Monitor.

• pioglitazone

  Minor (1)protriptyline increases effects of pioglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• pirbuterol

  Monitor Closely (1)protriptyline increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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

  Serious - Use Alternative (1)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.

• pleurisy root

  Minor (1)pleurisy root decreases effects of protriptyline by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.

• posaconazole

  Monitor Closely (1)protriptyline and posaconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• pralidoxime

  Monitor Closely (1)pralidoxime and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• pregabalin

  Monitor Closely (1)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

  Monitor Closely (1)primidone and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)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.

• procainamide

  Contraindicated (1)protriptyline and procainamide both increase QTc interval. Contraindicated.

• procarbazine

  Contraindicated (1)procarbazine and protriptyline both increase serotonin levels. Contraindicated. Combination is contraindicated within 2 weeks of MAOI use.

• prochlorperazine

  Monitor Closely (2)prochlorperazine and protriptyline both increase QTc interval. Use Caution/Monitor.
  
  prochlorperazine and protriptyline both increase sedation. Use Caution/Monitor.Minor (2)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

  Minor (1)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

  Serious - Use Alternative (1)promazine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)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

  Monitor Closely (2)promethazine and protriptyline both increase QTc interval. Use Caution/Monitor.
  
  promethazine and protriptyline both increase sedation. Use Caution/Monitor.Minor (2)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.

• propantheline

  Monitor Closely (1)propantheline and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• propofol

  Monitor Closely (1)propofol and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)propofol, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• propylhexedrine

  Monitor Closely (1)protriptyline increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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

  Serious - Use Alternative (1)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.

• pyridostigmine

  Monitor Closely (1)pyridostigmine increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• quazepam

  Monitor Closely (1)quazepam and protriptyline both increase sedation. Use Caution/Monitor.

• quetiapine

  Monitor Closely (2)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.

• quinidine

  Contraindicated (1)quinidine and protriptyline both increase QTc interval. Contraindicated.

• quinine

  Monitor Closely (1)protriptyline and quinine both increase QTc interval. Use Caution/Monitor.

• ramelteon

  Monitor Closely (1)protriptyline and ramelteon both increase sedation. Use Caution/Monitor.

• ranolazine

  Monitor Closely (1)protriptyline and ranolazine both increase QTc interval. Modify Therapy/Monitor Closely.

• rapacuronium

  Monitor Closely (1)rapacuronium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• rasagiline

  Serious - Use Alternative (1)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.

• remimazolam

  Monitor Closely (1)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.

• repaglinide

  Minor (1)protriptyline increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• ribociclib

  Serious - Use Alternative (1)ribociclib increases toxicity of protriptyline by QTc interval. Avoid or Use Alternate Drug.

• rifabutin

  Monitor Closely (1)rifabutin decreases levels of protriptyline by increasing metabolism. Use Caution/Monitor.

• rilpivirine

  Monitor Closely (1)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

  Monitor Closely (2)protriptyline and risperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  risperidone and protriptyline both increase sedation. Use Caution/Monitor.

• rivastigmine

  Monitor Closely (1)rivastigmine increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• rizatriptan

  Monitor Closely (1)rizatriptan and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• rocuronium

  Monitor Closely (1)rocuronium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• rolapitant

  Monitor Closely (1)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

  Monitor Closely (1)protriptyline and romidepsin both increase QTc interval. Modify Therapy/Monitor Closely.

• rosiglitazone

  Minor (1)protriptyline increases effects of rosiglitazone by pharmacodynamic synergism. Minor/Significance Unknown.

• safinamide

  Contraindicated (1)protriptyline, safinamide. Either increases toxicity of the other by serotonin levels. Contraindicated. Concomitant use could result in life-threatening serotonin syndrome.

• sage

  Minor (1)protriptyline and sage both increase sedation. Minor/Significance Unknown.

• salmeterol

  Monitor Closely (1)protriptyline increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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.

• SAMe

  Monitor Closely (1)protriptyline and SAMe both increase serotonin levels. Modify Therapy/Monitor Closely.

• saxagliptin

  Minor (1)protriptyline increases effects of saxagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

• scopolamine

  Monitor Closely (1)scopolamine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• scullcap

  Monitor Closely (1)protriptyline and scullcap both increase sedation. Use Caution/Monitor.

• secobarbital

  Monitor Closely (1)secobarbital and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)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.

• selegiline

  Contraindicated (1)selegiline and protriptyline both increase serotonin levels. Contraindicated. Concurrent use or use within 14 days of selegiline treatment is contraindicated

• selegiline transdermal

  Serious - Use Alternative (1)selegiline transdermal and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• selinexor

  Serious - Use Alternative (1)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.

• selpercatinib

  Monitor Closely (1)selpercatinib increases toxicity of protriptyline by QTc interval. Use Caution/Monitor.

• sertraline

  Serious - Use Alternative (1)sertraline and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• sevoflurane

  Monitor Closely (1)sevoflurane and protriptyline both increase sedation. Use Caution/Monitor.Minor (1)sevoflurane, protriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• shepherd's purse

  Monitor Closely (1)protriptyline and shepherd's purse both increase sedation. Use Caution/Monitor.

• sitagliptin

  Minor (1)protriptyline increases effects of sitagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

• sodium oxybate

  Serious - Use Alternative (1)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.

• sodium sulfate/?magnesium sulfate/potassium chloride

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)solifenacin and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• sorafenib

  Monitor Closely (1)sorafenib and protriptyline both increase QTc interval. Use Caution/Monitor.

• sotalol

  Contraindicated (1)protriptyline and sotalol both increase QTc interval. Contraindicated.

• St John's Wort

  Serious - Use Alternative (1)protriptyline and St John's Wort both increase serotonin levels. Avoid or Use Alternate Drug.

• stiripentol

  Monitor Closely (1)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

  Monitor Closely (1)succinylcholine increases and protriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• sufentanil

  Monitor Closely (1)sufentanil and protriptyline both increase sedation. Use Caution/Monitor.

• sufentanil SL

  Monitor Closely (1)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

  Monitor Closely (1)protriptyline and sulfamethoxazole both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)sulfamethoxazole decreases levels of protriptyline by unspecified interaction mechanism. Minor/Significance Unknown.

• sumatriptan

  Monitor Closely (1)sumatriptan and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• sumatriptan intranasal

  Monitor Closely (1)sumatriptan intranasal and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• suvorexant

  Monitor Closely (1)suvorexant and protriptyline both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary

• tapentadol

  Monitor Closely (2)protriptyline and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  tapentadol and protriptyline both increase sedation. Use Caution/Monitor.

• tedizolid

  Serious - Use Alternative (1)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.

• telavancin

  Monitor Closely (1)protriptyline and telavancin both increase QTc interval. Modify Therapy/Monitor Closely.

• temazepam

  Monitor Closely (1)temazepam and protriptyline both increase sedation. Use Caution/Monitor.

• terbinafine

  Monitor Closely (1)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

  Monitor Closely (1)protriptyline increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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

  Monitor Closely (1)thioridazine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)thioridazine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)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.

• thiothixene

  Monitor Closely (1)thiothixene and protriptyline both increase sedation. Use Caution/Monitor.

• tiotropium

  Monitor Closely (1)tiotropium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• tolazamide

  Minor (1)protriptyline increases effects of tolazamide by pharmacodynamic synergism. Minor/Significance Unknown.

• tolbutamide

  Minor (1)protriptyline increases effects of tolbutamide by pharmacodynamic synergism. Minor/Significance Unknown.

• tolterodine

  Monitor Closely (1)tolterodine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• topiramate

  Monitor Closely (1)protriptyline and topiramate both increase sedation. Modify Therapy/Monitor Closely.

• tramadol

  Monitor Closely (2)protriptyline and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  tramadol and protriptyline both increase sedation. Use Caution/Monitor.

• tranylcypromine

  Contraindicated (1)tranylcypromine and protriptyline both increase serotonin levels. Contraindicated.

• trazodone

  Monitor Closely (2)protriptyline and trazodone both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  protriptyline and trazodone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)protriptyline and trazodone both increase QTc interval. Avoid or Use Alternate Drug.
  
  trazodone and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• triazolam

  Monitor Closely (1)triazolam and protriptyline both increase sedation. Use Caution/Monitor.

• triclofos

  Monitor Closely (1)triclofos and protriptyline both increase sedation. Use Caution/Monitor.

• trifluoperazine

  Monitor Closely (1)trifluoperazine and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)trifluoperazine and protriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)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.

• trihexyphenidyl

  Monitor Closely (1)trihexyphenidyl and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. Potential for additive anticholinergic effects.

• trimethoprim

  Monitor Closely (1)protriptyline and trimethoprim both increase QTc interval. Modify Therapy/Monitor Closely.

• trimipramine

  Monitor Closely (2)protriptyline and trimipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  protriptyline and trimipramine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)protriptyline and trimipramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  protriptyline and trimipramine both increase serotonin levels. Avoid or Use Alternate Drug.

• triprolidine

  Monitor Closely (1)triprolidine and protriptyline both increase sedation. Use Caution/Monitor.

• tropisetron

  Monitor Closely (1)protriptyline and tropisetron both increase QTc interval. Modify Therapy/Monitor Closely.

• trospium chloride

  Monitor Closely (1)trospium chloride and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• umeclidinium bromide/vilanterol inhaled

  Serious - Use Alternative (2)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

• valerian

  Monitor Closely (1)valerian and protriptyline both increase sedation. Use Caution/Monitor.

• vandetanib

  Serious - Use Alternative (1)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.

• vasopressin

  Minor (1)protriptyline increases effects of vasopressin by pharmacodynamic synergism. Minor/Significance Unknown.

• vecuronium

  Monitor Closely (1)vecuronium and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• vemurafenib

  Serious - Use Alternative (1)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

  Monitor Closely (1)protriptyline and venlafaxine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)venlafaxine and protriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• verapamil

  Minor (1)verapamil increases levels of protriptyline by decreasing metabolism. Minor/Significance Unknown.

• vilanterol/fluticasone furoate inhaled

  Serious - Use Alternative (2)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

  Serious - Use Alternative (1)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. .

• vildagliptin

  Minor (1)protriptyline increases effects of vildagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

• voclosporin

  Monitor Closely (1)voclosporin, protriptyline. Either increases effects of the other by QTc interval. Use Caution/Monitor.

• voriconazole

  Monitor Closely (1)protriptyline and voriconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• vortioxetine

  Serious - Use Alternative (1)protriptyline, vortioxetine. Either increases effects of the other by serotonin levels. Avoid or Use Alternate Drug.

• xylometazoline

  Monitor Closely (1)protriptyline increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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

  Serious - Use Alternative (1)yohimbe, protriptyline. Mechanism: unspecified interaction mechanism. Contraindicated. May cause increase or decrease in blood pressure.

• yohimbine

  Monitor Closely (1)protriptyline increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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.

• ziconotide

  Monitor Closely (1)protriptyline and ziconotide both increase sedation. Use Caution/Monitor.

• ziprasidone

  Monitor Closely (1)ziprasidone and protriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)protriptyline and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.

• zolmitriptan

  Monitor Closely (1)zolmitriptan and protriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• zolpidem

  Minor (1)zolpidem, protriptyline. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive CNS depression.