nortriptyline (Rx)

Depression

25mg PO q6-8hr

No more than 150 mg/day

Dosing considerations

• Total daily dose can be given HS
• To discontinue therapy, gradually taper dose to minimize incidence of withdrawal symptoms and allow for detection of re-emerging symptoms

Chronic Urticaria, Nocturnal Pruritus, Angioedema (Off-label)

75mg/day PO

Smoking Cessation (Off-label)

25 mg PO qDay; start 1-2 weeks before quit date; may titrate to 75-100 mg/day 10-28 days prior to selected quit date; titrate dose to 75-100 mg/day; continue therapy for 12 weeks or more after quit day

ADHD (Off-label)

25 mg PO q6-8hr

Postherpetic Neuralgia (Off-label)

10-25 mg PO qHS; may increase q3-5days in 10 mg increments qDay up to 160 mg qHS or divided q12hr if tolerated

Dosing Modifications

Hepatic impairment: Administer lower dose and titrate at a slower rate

Depression (Off-label)

<6 years: Safety and efficacy not established

6-12 years: 1-3 mg/kg/day PO divided q6-8hr, OR 10-20 mg/day PO divided q6-8hr  

>12 years: 30-50 mg PO qDay, divided or single dose

See Black Box Warning

Nocturnal Enuresis (Off-label)

6-7 years (20-25 kg): 10 mg PO qHS

8-11 years (26-35 kg): 10-20 mg PO qHS

>11 years (36-54 kg): 25-35 mg PO qHS

ADHD (Off-label)

0.5 mg/kg/day PO, titrated to maximum 2 mg/kg/day or 100 mg, whichever is less

Depression

Initial: 30-50 mg PO qDay or in divided doses

May increase to 75-100 mg/day if tolerated

Contraindicated (17)

• disopyramide

  nortriptyline and disopyramide both increase QTc interval. Contraindicated.

• dronedarone

  dronedarone will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated.

• ibutilide

  nortriptyline and ibutilide both increase QTc interval. Contraindicated.

• indapamide

  nortriptyline and indapamide both increase QTc interval. Contraindicated.

• iobenguane I 123

  nortriptyline 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 nortriptyline both increase serotonin levels. Contraindicated.

• pentamidine

  nortriptyline and pentamidine both increase QTc interval. Contraindicated.

• phenelzine

  phenelzine and nortriptyline both increase serotonin levels. Contraindicated.

• pimozide

  nortriptyline and pimozide both increase QTc interval. Contraindicated.

• procainamide

  nortriptyline and procainamide both increase QTc interval. Contraindicated.

• procarbazine

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

• quinidine

  quinidine and nortriptyline both increase QTc interval. Contraindicated.

• safinamide

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

• selegiline

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

• sotalol

  nortriptyline and sotalol both increase QTc interval. Contraindicated.

• thioridazine

  thioridazine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated.

• tranylcypromine

  tranylcypromine and nortriptyline both increase serotonin levels. Contraindicated.

Serious - Use Alternative (137)

• albuterol

  nortriptyline, 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

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

• amitriptyline

  amitriptyline and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  amitriptyline and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• amoxapine

  amoxapine and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  amoxapine and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• arformoterol

  nortriptyline, 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

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

• artemether

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

• artemether/lumefantrine

  artemether/lumefantrine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
  
  nortriptyline and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

• benzphetamine

  nortriptyline, benzphetamine. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• buprenorphine

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

• buspirone

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

• calcium/magnesium/potassium/sodium oxybates

  nortriptyline, 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 nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• citalopram

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

• clarithromycin

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

• clomipramine

  clomipramine and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  clomipramine and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• clonidine

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

• cyclobenzaprine

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

• dacomitinib

  dacomitinib will increase the level or effect of nortriptyline 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 nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  desipramine and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• desvenlafaxine

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

• dexfenfluramine

  nortriptyline, 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

  nortriptyline, 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

  nortriptyline, 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

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

• diethylpropion

  nortriptyline, 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

  nortriptyline, 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

  nortriptyline and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.
  
  dofetilide increases toxicity of nortriptyline by QTc interval. Avoid or Use Alternate Drug.

• dolasetron

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

• dopamine

  nortriptyline, 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

  nortriptyline, 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 nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  doxepin and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• dronedarone

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

• droperidol

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

• duloxetine

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

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

• encorafenib

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

• ephedrine

  nortriptyline, 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 nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  nortriptyline, 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 nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  nortriptyline, 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

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

• erythromycin ethylsuccinate

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

• erythromycin lactobionate

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

• erythromycin stearate

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

• escitalopram

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

• fenfluramine

  nortriptyline, 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 nortriptyline 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

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

• fluoxetine

  fluoxetine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
  
  fluoxetine and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• fluphenazine

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

• fluvoxamine

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

• formoterol

  nortriptyline and formoterol both increase QTc interval. Avoid or Use Alternate Drug.
  
  nortriptyline, 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 nortriptyline by decreasing metabolism. Avoid or Use Alternate Drug.

• givosiran

  givosiran will increase the level or effect of nortriptyline 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, nortriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• guanfacine

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

• haloperidol

  haloperidol will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
  
  nortriptyline and haloperidol both increase QTc interval. Avoid or Use Alternate Drug.

• hydroxychloroquine sulfate

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

• imipramine

  imipramine and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  imipramine and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• iobenguane I 131

  nortriptyline 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

  nortriptyline, 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

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

• ivosidenib

  ivosidenib and nortriptyline 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

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

• lefamulin

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

• levalbuterol

  nortriptyline, levalbuterol. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• levoketoconazole

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

• levomilnacipran

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

• linezolid

  linezolid and nortriptyline 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

  nortriptyline, 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 nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  lofepramine and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• lorcaserin

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

• lumefantrine

  lumefantrine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
  
  nortriptyline and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.

• macimorelin

  macimorelin and nortriptyline 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 nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  maprotiline and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• mefloquine

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

• meperidine

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

• metaproterenol

  nortriptyline, 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

  nortriptyline, 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 nortriptyline 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

  nortriptyline, 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

  nortriptyline, 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

  nortriptyline, 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 nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• mirtazapine

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

• mobocertinib

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

• moxifloxacin

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

• nefazodone

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

• netupitant/palonosetron

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

• nilotinib

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

• norepinephrine

  nortriptyline, 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.

• octreotide

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

• octreotide (Antidote)

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

• olopatadine intranasal

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

• ondansetron

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

• ozanimod

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

• paroxetine

  paroxetine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
  
  paroxetine and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• perphenazine

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

• phendimetrazine

  nortriptyline, 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

  nortriptyline, 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

  nortriptyline, 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

  nortriptyline, 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

  nortriptyline, 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

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

• propylhexedrine

  nortriptyline, 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.

• protriptyline

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

• pseudoephedrine

  nortriptyline 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.

• quinidine

  quinidine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• rasagiline

  rasagiline and nortriptyline 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 will increase the level or effect of nortriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  ribociclib increases toxicity of nortriptyline by QTc interval. Avoid or Use Alternate Drug.

• salmeterol

  nortriptyline, 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 nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• selinexor

  selinexor, nortriptyline. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.

• serdexmethylphenidate/dexmethylphenidate

  nortriptyline, serdexmethylphenidate/dexmethylphenidate. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.

• sertraline

  sertraline and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.
  
  sertraline and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• sodium oxybate

  nortriptyline, 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

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

• tedizolid

  tedizolid, nortriptyline. 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

  nortriptyline, 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 nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• toremifene

  nortriptyline and toremifene both increase QTc interval. Avoid or Use Alternate Drug. Concurrent use of toremifene with agents causing QT prolongation should be avoided. If concomitant use is required it's recommended that toremifene be interrupted. If interruption not possible, patients requiring therapy with a drug that prolongs QT should be closely monitored. ECGs should be obtained for high risk patients.

• trazodone

  nortriptyline and trazodone both increase QTc interval. Avoid or Use Alternate Drug.
  
  trazodone and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• trifluoperazine

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

• trimipramine

  nortriptyline and trimipramine both increase QTc interval. Avoid or Use Alternate Drug.
  
  nortriptyline and trimipramine both increase serotonin levels. Avoid or Use Alternate Drug.

• umeclidinium bromide/vilanterol inhaled

  nortriptyline 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.
  
  nortriptyline 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

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

• venlafaxine

  venlafaxine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.
  
  venlafaxine and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• vilanterol/fluticasone furoate inhaled

  nortriptyline 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
  
  nortriptyline 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

  nortriptyline, 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

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

• xylometazoline

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

• yohimbine

  nortriptyline, 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

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

Monitor Closely (354)

• 5-HTP

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

• abiraterone

  abiraterone increases levels of nortriptyline 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 nortriptyline 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 nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• albuterol

  nortriptyline increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  albuterol and nortriptyline both increase QTc interval. Use Caution/Monitor.

• alfentanil

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

• alfuzosin

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

• almotriptan

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

• alprazolam

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

• amifampridine

  nortriptyline 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

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

• amisulpride

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

• amitriptyline

  amitriptyline and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  amitriptyline and nortriptyline both increase sedation. Use Caution/Monitor.

• amobarbital

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

• amoxapine

  amoxapine and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  amoxapine and nortriptyline both increase sedation. Use Caution/Monitor.

• anagrelide

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

• anticholinergic/sedative combos

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

• apomorphine

  nortriptyline and apomorphine both increase sedation. Use Caution/Monitor.
  
  apomorphine and nortriptyline both increase QTc interval. Use Caution/Monitor.

• arformoterol

  nortriptyline increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  arformoterol and nortriptyline both increase QTc interval. Use Caution/Monitor.

• aripiprazole

  aripiprazole and nortriptyline both increase sedation. Use Caution/Monitor.
  
  aripiprazole and nortriptyline both increase QTc interval. Use Caution/Monitor.

• armodafinil

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

• asenapine

  asenapine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  asenapine and nortriptyline both increase QTc interval. Use Caution/Monitor.

• asenapine transdermal

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

• atazanavir

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

• atomoxetine

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

• atracurium

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

• atropine

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

• atropine IV/IM

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

• azelastine

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

• azithromycin

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

• baclofen

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

• bedaquiline

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

• belladonna alkaloids

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

• belladonna and opium

  belladonna and opium and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  belladonna and opium and nortriptyline both increase sedation. Use Caution/Monitor.

• benperidol

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

• benzhydrocodone/acetaminophen

  benzhydrocodone/acetaminophen, nortriptyline. 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

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

• benztropine

  benztropine and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. Additive anticholinergic adverse effects may be seen with concurrent use.

• bethanechol

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

• brompheniramine

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

• buprenorphine

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

• buprenorphine buccal

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

• buprenorphine subdermal implant

  nortriptyline, 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

  nortriptyline, 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

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

• butabarbital

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

• butalbital

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

• butorphanol

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

• caffeine

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

• carbachol

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

• carbinoxamine

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

• carisoprodol

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

• celecoxib

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

• cenobamate

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

• ceritinib

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

• cevimeline

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

• chloral hydrate

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

• chlordiazepoxide

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

• chloroquine

  chloroquine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  chloroquine increases toxicity of nortriptyline by QTc interval. Use Caution/Monitor.

• chlorpheniramine

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

• chlorpromazine

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

• chlorzoxazone

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

• cimetidine

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

• cinnarizine

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

• cisatracurium

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

• clemastine

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

• clobazam

  clobazam will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly.
  
  nortriptyline, 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 nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  clomipramine and nortriptyline both increase sedation. Use Caution/Monitor.

• clonazepam

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

• clorazepate

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

• clozapine

  clozapine and nortriptyline both increase sedation. Use Caution/Monitor.
  
  clozapine and nortriptyline both increase QTc interval. Use Caution/Monitor.

• cobicistat

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

• cocaine topical

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

• codeine

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

• crizotinib

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

• cyclizine

  cyclizine and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  cyclizine and nortriptyline both increase sedation. Use Caution/Monitor.

• cyclobenzaprine

  cyclobenzaprine and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  cyclobenzaprine and nortriptyline both increase sedation. Use Caution/Monitor.

• cyclosporine

  cyclosporine will increase the level or effect of nortriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cyproheptadine

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

• dantrolene

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

• daridorexant

  nortriptyline 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 will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  darifenacin and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• dasatinib

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

• debrisoquine

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

• degarelix

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

• desflurane

  desflurane and nortriptyline both increase sedation. Use Caution/Monitor.
  
  desflurane and nortriptyline both increase QTc interval. Use Caution/Monitor.

• desipramine

  desipramine and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  desipramine and nortriptyline both increase sedation. Use Caution/Monitor.

• desvenlafaxine

  desvenlafaxine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mg

• deutetrabenazine

  nortriptyline and deutetrabenazine both increase sedation. Use Caution/Monitor.
  
  deutetrabenazine and nortriptyline both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).

• dexchlorpheniramine

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

• dexfenfluramine

  nortriptyline increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  nortriptyline and dexfenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.

• dexmedetomidine

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

• dexmethylphenidate

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

• dextroamphetamine

  nortriptyline increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  nortriptyline and dextroamphetamine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  nortriptyline increases effects of dextroamphetamine by unknown mechanism. Use Caution/Monitor.

• dextroamphetamine transdermal

  nortriptyline will increase the level or effect of dextroamphetamine transdermal by pharmacodynamic synergism. Modify Therapy/Monitor Closely. May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in dextroamphetamine levels in brain; May be potentiate cardiovascular effects. Monitor frequently and adjust or use an alternant based on clinical response.

• dextromoramide

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

• diamorphine

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

• diazepam

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

• diazepam intranasal

  diazepam intranasal, nortriptyline. 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 nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• diethylpropion

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

• difelikefalin

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

• difenoxin hcl

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

• dihydroergotamine

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

• dihydroergotamine intranasal

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

• dimenhydrinate

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

• diphenhydramine

  diphenhydramine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and nortriptyline both increase sedation. Use Caution/Monitor.

• diphenoxylate hcl

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

• dipipanone

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

• dobutamine

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

• dolasetron

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

• donepezil

  donepezil increases and nortriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  donepezil and nortriptyline both increase QTc interval. Use Caution/Monitor.

• dopamine

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

• dopexamine

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

• doxepin

  doxepin and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  doxepin and nortriptyline both increase sedation. Use Caution/Monitor.

• doxylamine

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

• droperidol

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

• duloxetine

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

• echothiophate iodide

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

• efavirenz

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

• eletriptan

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

• eliglustat

  eliglustat increases levels of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the concomitant drug and titrate to clinical effect.
  
  eliglustat and nortriptyline both increase QTc interval. Use Caution/Monitor.

• entrectinib

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

• ephedrine

  nortriptyline increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  nortriptyline increases effects of ephedrine by unknown mechanism. Use Caution/Monitor.

• epinephrine

  nortriptyline increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  nortriptyline increases effects of epinephrine by unknown mechanism. Use Caution/Monitor.

• epinephrine inhaled

  nortriptyline 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

  nortriptyline increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  nortriptyline increases effects of epinephrine racemic by unknown mechanism. Use Caution/Monitor.

• ergotamine

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

• eribulin

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

• escitalopram

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

• esketamine intranasal

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

• estazolam

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

• ethanol

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

• etomidate

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

• ezogabine

  ezogabine, nortriptyline. 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 nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

• fenfluramine

  nortriptyline increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  nortriptyline and fenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  fenfluramine, nortriptyline. 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 nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• fingolimod

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

• flavoxate

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

• flecainide

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

• fluoxetine

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

• fluphenazine

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

• flurazepam

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

• fluvoxamine

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

• formoterol

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

• foscarnet

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

• fostemsavir

  nortriptyline and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

• frovatriptan

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

• gabapentin

  gabapentin, nortriptyline. 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, nortriptyline. 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 nortriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ganaxolone

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

• gemifloxacin

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

• gilteritinib

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

• glycopyrrolate

  glycopyrrolate and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  nortriptyline increases levels of glycopyrrolate by unknown mechanism. Use Caution/Monitor.

• glycopyrrolate inhaled

  glycopyrrolate inhaled and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  nortriptyline increases levels of glycopyrrolate inhaled by unknown mechanism. Use Caution/Monitor.

• glycopyrronium tosylate topical

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

• granisetron

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

• haloperidol

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

• henbane

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

• homatropine

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

• huperzine A

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

• hydrocodone

  hydrocodone, nortriptyline. 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 nortriptyline both increase sedation. Use Caution/Monitor.

• hydroxyzine

  hydroxyzine and nortriptyline both increase sedation. Use Caution/Monitor.
  
  hydroxyzine and nortriptyline both increase QTc interval. Use Caution/Monitor.

• hyoscyamine

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

• hyoscyamine spray

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

• iloperidone

  nortriptyline and iloperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  iloperidone and nortriptyline both increase sedation. Use Caution/Monitor.

• imatinib

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

• imipramine

  imipramine and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  imipramine and nortriptyline both increase sedation. Use Caution/Monitor.

• indacaterol, inhaled

  indacaterol, inhaled, nortriptyline. 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 nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. Due to the poor systemic absorption of ipratropium, interaction unlikely at regularly recommended dosages.

• isoflurane

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

• isoniazid

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

• isoproterenol

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

• itraconazole

  itraconazole and nortriptyline both increase QTc interval. Use Caution/Monitor.

• ketamine

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

• ketotifen, ophthalmic

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

• L-tryptophan

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

• lapatinib

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

• lasmiditan

  lasmiditan, nortriptyline. 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.
  
  nortriptyline increases effects of lasmiditan by serotonin levels. Use Caution/Monitor. Coadministration may increase risk of serotonin syndrome.

• lemborexant

  lemborexant, nortriptyline. 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

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

• levofloxacin

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

• levoketoconazole

  levoketoconazole will increase the level or effect of nortriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• levorphanol

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

• lisdexamfetamine

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

  nortriptyline and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  lithium and nortriptyline both increase QTc interval. Use Caution/Monitor.

• lofepramine

  lofepramine and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  lofepramine and nortriptyline both increase sedation. Use Caution/Monitor.

• lofexidine

  nortriptyline and lofexidine both increase sedation. Use Caution/Monitor.
  
  nortriptyline decreases effects of lofexidine by unspecified interaction mechanism. Use Caution/Monitor.

• loprazolam

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

• lorazepam

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

• lorcaserin

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

• lormetazepam

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

• loxapine

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

• loxapine inhaled

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

• lsd

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

• lurasidone

  lurasidone increases effects of nortriptyline by Other (see comment). Use Caution/Monitor. Comment: Potential for additive CNS effects .

• maprotiline

  maprotiline and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  maprotiline and nortriptyline both increase sedation. Use Caution/Monitor.

• maraviroc

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

• marijuana

  marijuana will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  nortriptyline and marijuana both increase sedation. Use Caution/Monitor.

• meclizine

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

• melatonin

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

• meperidine

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

• meprobamate

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

• metaproterenol

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

• metaxalone

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

• methadone

  nortriptyline and methadone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  methadone and nortriptyline both increase sedation. Use Caution/Monitor.

• methamphetamine

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

• methocarbamol

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

• methscopolamine

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

• methylenedioxymethamphetamine

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

• methylphenidate

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

• methylphenidate transdermal

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

• midazolam

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

• midazolam intranasal

  midazolam intranasal, nortriptyline. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

• midodrine

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

• mifepristone

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

• mirabegron

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

• mirtazapine

  nortriptyline and mirtazapine both increase sedation. Use Caution/Monitor.
  
  nortriptyline and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely.

• modafinil

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

• morphine

  morphine and nortriptyline both increase sedation. Use Caution/Monitor.
  
  nortriptyline and morphine both increase serotonin levels. Modify Therapy/Monitor Closely.

• motherwort

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

• moxonidine

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

• nabilone

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

• nalbuphine

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

• naratriptan

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

• nefopam

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

• neostigmine

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

• nilotinib

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

• norepinephrine

  nortriptyline increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.
  
  nortriptyline increases effects of norepinephrine by unknown mechanism. Use Caution/Monitor.

• ofloxacin

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

• olanzapine

  olanzapine and nortriptyline both increase sedation. Use Caution/Monitor.
  
  olanzapine and nortriptyline both increase QTc interval. Use Caution/Monitor.

• oliceridine

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

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

• opium tincture

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

• orphenadrine

  nortriptyline and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  orphenadrine and nortriptyline both increase sedation. Use Caution/Monitor.

• osilodrostat

  osilodrostat and nortriptyline both increase QTc interval. Use Caution/Monitor.

• osimertinib

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

• oxybutynin

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

• oxybutynin topical

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

• oxybutynin transdermal

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

• oxycodone

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

• oxymetazoline intranasal

  nortriptyline 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 nortriptyline both increase sedation. Use Caution/Monitor.

• ozanimod

  ozanimod and nortriptyline 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

  nortriptyline and paliperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  paliperidone and nortriptyline both increase sedation. Use Caution/Monitor.

• pancuronium

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

• papaveretum

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

• papaverine

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

• parecoxib

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

• paroxetine

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

• pasireotide

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

• pazopanib

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

• peginterferon alfa 2b

  peginterferon alfa 2b, nortriptyline. 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 nortriptyline both increase sedation. Use Caution/Monitor.
  
  nortriptyline and pentazocine both increase serotonin levels. Modify Therapy/Monitor Closely.

• pentobarbital

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

• perphenazine

  perphenazine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  perphenazine and nortriptyline both increase sedation. Use Caution/Monitor.

• phendimetrazine

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

• phenobarbital

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

• phentermine

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

• phenylephrine

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

• phenylephrine ophthalmic

  nortriptyline, 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

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

• pholcodine

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

• physostigmine

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

• pilocarpine

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

• pimozide

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

• pirbuterol

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

• posaconazole

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

• pralidoxime

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

• pregabalin

  pregabalin, nortriptyline. 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 nortriptyline both increase sedation. Use Caution/Monitor.

• prochlorperazine

  prochlorperazine and nortriptyline both increase QTc interval. Use Caution/Monitor.
  
  prochlorperazine and nortriptyline both increase sedation. Use Caution/Monitor.

• promethazine

  promethazine and nortriptyline both increase QTc interval. Use Caution/Monitor.
  
  promethazine and nortriptyline both increase sedation. Use Caution/Monitor.

• propafenone

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

• propantheline

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

• propofol

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

• propylhexedrine

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

• protriptyline

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

• pyridostigmine

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

• quazepam

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

• quetiapine

  quetiapine and nortriptyline both increase sedation. Use Caution/Monitor.
  
  quetiapine, nortriptyline. 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.

• quinacrine

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

• quinine

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

• ramelteon

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

• ranolazine

  ranolazine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  nortriptyline and ranolazine both increase QTc interval. Modify Therapy/Monitor Closely.

• rapacuronium

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

• remimazolam

  remimazolam, nortriptyline. 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 nortriptyline by increasing metabolism. Use Caution/Monitor.

• rilpivirine

  rilpivirine increases toxicity of nortriptyline 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

  nortriptyline and risperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  risperidone and nortriptyline both increase sedation. Use Caution/Monitor.

• ritonavir

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

• rizatriptan

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

• rocuronium

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

• romidepsin

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

• salmeterol

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

• SAMe

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

• scopolamine

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

• scullcap

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

• secobarbital

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

• selpercatinib

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

• sertraline

  sertraline will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely.

• sevoflurane

  sevoflurane and nortriptyline both increase sedation. Use Caution/Monitor.
  
  sevoflurane and nortriptyline both increase QTc interval. Use Caution/Monitor.

• shepherd's purse

  nortriptyline 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 nortriptyline 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 nortriptyline 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

  nortriptyline, 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 nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  solifenacin and nortriptyline both increase QTc interval. Use Caution/Monitor.

• sorafenib

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

• stiripentol

  stiripentol, nortriptyline. 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 nortriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• sufentanil

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

• sufentanil SL

  sufentanil SL, nortriptyline. 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

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

• sumatriptan

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

• sumatriptan intranasal

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

• suvorexant

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

• tacrolimus

  tacrolimus and nortriptyline both increase QTc interval. Use Caution/Monitor.

• tapentadol

  tapentadol and nortriptyline both increase sedation. Use Caution/Monitor.
  
  nortriptyline and tapentadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• telavancin

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

• temazepam

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

• terbutaline

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

• thioridazine

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

• thiothixene

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

• tiotropium

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

• tipranavir

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

• tolterodine

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

• topiramate

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

• tramadol

  tramadol and nortriptyline both increase sedation. Use Caution/Monitor.
  
  nortriptyline and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.

• trazodone

  nortriptyline and trazodone both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  nortriptyline and trazodone both increase sedation. Use Caution/Monitor.

• triazolam

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

• triclofos

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

• trifluoperazine

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

• trihexyphenidyl

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

• trimethoprim

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

• trimipramine

  nortriptyline and trimipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  nortriptyline and trimipramine both increase sedation. Use Caution/Monitor.

• triprolidine

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

• tropisetron

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

• trospium chloride

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

• valbenazine

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

• valerian

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

• vecuronium

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

• venlafaxine

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

• voclosporin

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

• voriconazole

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

• xylometazoline

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

• yohimbine

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

• ziconotide

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

• ziprasidone

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

• zolmitriptan

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

Minor (71)

• acarbose

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

• amobarbital

  amobarbital, nortriptyline. 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

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

• atropine IV/IM

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

• bazedoxifene/conjugated estrogens

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

• brimonidine

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

• butabarbital

  butabarbital, nortriptyline. 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, nortriptyline. 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 nortriptyline by increasing metabolism. Minor/Significance Unknown.

• chlorpromazine

  nortriptyline, chlorpromazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  nortriptyline, chlorpromazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• chlorpropamide

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

• conjugated estrogens

  conjugated estrogens, nortriptyline. 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, nortriptyline. 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, nortriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• dexmethylphenidate

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

• estradiol

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

• estropipate

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

• eucalyptus

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

• fluphenazine

  nortriptyline, fluphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  nortriptyline, fluphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• glimepiride

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

• glipizide

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

• glyburide

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

• hydroxyprogesterone caproate

  hydroxyprogesterone caproate, nortriptyline. 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

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

• insulin detemir

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

• insulin glargine

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

• insulin glulisine

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

• insulin lispro

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

• insulin NPH

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

• insulin regular human

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

• isoproterenol

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

• ketamine

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

• lithium

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

• mestranol

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

• metformin

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

• miglitol

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

• nateglinide

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

• panax ginseng

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

• pentobarbital

  pentobarbital, nortriptyline. 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

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

• phenobarbital

  phenobarbital, nortriptyline. 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

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

• pleurisy root

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

• primidone

  primidone, nortriptyline. 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

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

• progesterone micronized

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

• promazine

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

• promethazine

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

• propofol

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

• repaglinide

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

• rifampin

  rifampin decreases levels of nortriptyline by increasing metabolism. Minor/Significance Unknown.

• rosiglitazone

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

• sage

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

• saxagliptin

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

• secobarbital

  secobarbital, nortriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• serdexmethylphenidate/dexmethylphenidate

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

• sevoflurane

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

• sitagliptin

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

• sulfamethoxazole

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

• thioridazine

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

• tolazamide

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

• tolbutamide

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

• trifluoperazine

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

• vasopressin

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

• verapamil

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

• vildagliptin

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

• zolpidem

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

• 5-HTP

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

• abiraterone

  Monitor Closely (1)abiraterone increases levels of nortriptyline 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 nortriptyline 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)nortriptyline increases effects of acarbose by pharmacodynamic synergism. Minor/Significance Unknown.

• aclidinium

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

• albuterol

  Monitor Closely (2)albuterol and nortriptyline both increase QTc interval. Use Caution/Monitor.
  
  nortriptyline increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline, 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 nortriptyline both increase sedation. Use Caution/Monitor.

• alfuzosin

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

• almotriptan

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

• alprazolam

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

• amifampridine

  Monitor Closely (1)nortriptyline 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

  Monitor Closely (1)amiodarone will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.

• amisulpride

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

• amitriptyline

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

• amobarbital

  Monitor Closely (1)amobarbital and nortriptyline both increase sedation. Use Caution/Monitor.Minor (1)amobarbital, nortriptyline. 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 nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  amoxapine and nortriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)amoxapine and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  amoxapine and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• anagrelide

  Monitor Closely (1)anagrelide and nortriptyline both increase QTc interval. Use Caution/Monitor.

• anticholinergic/sedative combos

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

• apomorphine

  Monitor Closely (2)apomorphine and nortriptyline both increase QTc interval. Use Caution/Monitor.
  
  nortriptyline and apomorphine both increase sedation. Use Caution/Monitor.

• arformoterol

  Monitor Closely (2)arformoterol and nortriptyline both increase QTc interval. Use Caution/Monitor.
  
  nortriptyline increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline, 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 (2)aripiprazole and nortriptyline both increase QTc interval. Use Caution/Monitor.
  
  aripiprazole and nortriptyline both increase sedation. Use Caution/Monitor.

• armodafinil

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

• arsenic trioxide

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

• artemether

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

• artemether/lumefantrine

  Serious - Use Alternative (2)nortriptyline and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.
  
  artemether/lumefantrine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• asenapine

  Monitor Closely (2)asenapine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  asenapine and nortriptyline both increase QTc interval. Use Caution/Monitor.

• asenapine transdermal

  Monitor Closely (1)asenapine transdermal and nortriptyline both increase QTc interval. Use Caution/Monitor.

• atazanavir

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

• atomoxetine

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

• atracurium

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

• atropine

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

• atropine IV/IM

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

• azelastine

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

• azithromycin

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

• baclofen

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

• bazedoxifene/conjugated estrogens

  Minor (1)bazedoxifene/conjugated estrogens, nortriptyline. 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)nortriptyline and bedaquiline both increase QTc interval. Modify Therapy/Monitor Closely. ECG should be monitored closely

• belladonna alkaloids

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

• belladonna and opium

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

• benperidol

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

• benzhydrocodone/acetaminophen

  Monitor Closely (1)benzhydrocodone/acetaminophen, nortriptyline. 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)nortriptyline increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline, 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 nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. Additive anticholinergic adverse effects may be seen with concurrent use.

• bethanechol

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

• brimonidine

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

• brompheniramine

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

• buprenorphine

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

• buprenorphine buccal

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

• buprenorphine subdermal implant

  Monitor Closely (1)nortriptyline, 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)nortriptyline, 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)bupropion will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  nortriptyline increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

• buspirone

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

• butabarbital

  Monitor Closely (1)butabarbital and nortriptyline both increase sedation. Use Caution/Monitor.Minor (1)butabarbital, nortriptyline. 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 nortriptyline both increase sedation. Use Caution/Monitor.Minor (1)butalbital, nortriptyline. 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 nortriptyline both increase sedation. Use Caution/Monitor.

• caffeine

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

• carbamazepine

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

• carbinoxamine

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

• carisoprodol

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

• celecoxib

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

• cenobamate

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

• ceritinib

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

• cevimeline

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

• chloral hydrate

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

• chlordiazepoxide

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

• chloroquine

  Monitor Closely (2)chloroquine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  chloroquine increases toxicity of nortriptyline by QTc interval. Use Caution/Monitor.

• chlorpheniramine

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

• chlorpromazine

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

• chlorpropamide

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

• chlorzoxazone

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

• cimetidine

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

• cinnarizine

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

• cisatracurium

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

• citalopram

  Serious - Use Alternative (2)citalopram and nortriptyline 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 nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• clarithromycin

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

• clemastine

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

• clobazam

  Monitor Closely (2)clobazam will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly.
  
  nortriptyline, 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 nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  clomipramine and nortriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)clomipramine and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  clomipramine and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• clonazepam

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

• clonidine

  Serious - Use Alternative (1)nortriptyline 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 nortriptyline both increase sedation. Use Caution/Monitor.

• clozapine

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

• cobicistat

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

• cocaine topical

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

• codeine

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

• conjugated estrogens

  Minor (1)conjugated estrogens, nortriptyline. 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, nortriptyline. 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 nortriptyline 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 nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  cyclizine and nortriptyline both increase sedation. Use Caution/Monitor.

• cyclobenzaprine

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

• cyclosporine

  Monitor Closely (1)cyclosporine will increase the level or effect of nortriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cyproheptadine

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

• dacomitinib

  Serious - Use Alternative (1)dacomitinib will increase the level or effect of nortriptyline 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 nortriptyline both increase sedation. Use Caution/Monitor.

• daridorexant

  Monitor Closely (1)nortriptyline 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 (2)darifenacin will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  darifenacin and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• dasatinib

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

• debrisoquine

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

• degarelix

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

• desflurane

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

• desipramine

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

• desvenlafaxine

  Monitor Closely (1)desvenlafaxine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Desvenlafaxine inhibits CYP2D6; with higher desvenlafaxine doses (ie, 400 mg) decrease the CYP2D6 substrate dose by up to 50%; no dosage adjustment needed with desvenlafaxine doses <100 mgSerious - Use Alternative (1)nortriptyline and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

• deutetrabenazine

  Monitor Closely (2)nortriptyline and deutetrabenazine both increase sedation. Use Caution/Monitor.
  
  deutetrabenazine and nortriptyline both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).

• dexchlorpheniramine

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

• dexfenfluramine

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

• dexmethylphenidate

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

• dextroamphetamine

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

• dextroamphetamine transdermal

  Monitor Closely (1)nortriptyline will increase the level or effect of dextroamphetamine transdermal by pharmacodynamic synergism. Modify Therapy/Monitor Closely. May enhance the activity of tricyclic or sympathomimetic agents causing striking and sustained increases in dextroamphetamine levels in brain; May be potentiate cardiovascular effects. Monitor frequently and adjust or use an alternant based on clinical response.

• dextromethorphan

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

• dextromoramide

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

• diamorphine

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

• diazepam

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

• diazepam intranasal

  Monitor Closely (1)diazepam intranasal, nortriptyline. 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 nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• diethylpropion

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

• difenoxin hcl

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

• dihydroergotamine

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

• dihydroergotamine intranasal

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

• dimenhydrinate

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

• diphenhydramine

  Monitor Closely (3)diphenhydramine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  diphenhydramine and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and nortriptyline both increase sedation. Use Caution/Monitor.

• diphenoxylate hcl

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

• dipipanone

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

• disopyramide

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

• dobutamine

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

  Serious - Use Alternative (2)nortriptyline and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.
  
  dofetilide increases toxicity of nortriptyline by QTc interval. Avoid or Use Alternate Drug.

• dolasetron

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

• donepezil

  Monitor Closely (2)donepezil and nortriptyline both increase QTc interval. Use Caution/Monitor.
  
  donepezil increases and nortriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• dopamine

  Monitor Closely (1)nortriptyline increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline, 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)nortriptyline increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline, 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 nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  doxepin and nortriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)doxepin and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  doxepin and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• doxylamine

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

• dronedarone

  Contraindicated (1)dronedarone will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated.Serious - Use Alternative (1)nortriptyline and dronedarone both increase QTc interval. Avoid or Use Alternate Drug.

• droperidol

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

• duloxetine

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

• echothiophate iodide

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

• efavirenz

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

• eletriptan

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

• eliglustat

  Monitor Closely (2)eliglustat and nortriptyline both increase QTc interval. Use Caution/Monitor.
  
  eliglustat increases levels of nortriptyline 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

  Serious - Use Alternative (1)elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. 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 nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• entrectinib

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

• ephedrine

  Monitor Closely (2)nortriptyline increases effects of ephedrine by unknown mechanism. Use Caution/Monitor.
  
  nortriptyline increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline, 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)nortriptyline increases effects of epinephrine by unknown mechanism. Use Caution/Monitor.
  
  nortriptyline increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (2)epinephrine and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  nortriptyline, 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)nortriptyline 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)nortriptyline increases effects of epinephrine racemic by unknown mechanism. Use Caution/Monitor.
  
  nortriptyline increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (2)epinephrine racemic and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  nortriptyline, 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)nortriptyline and ergotamine both increase serotonin levels. Modify Therapy/Monitor Closely.

• eribulin

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

• erythromycin base

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

• erythromycin ethylsuccinate

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

• erythromycin lactobionate

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

• erythromycin stearate

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

• escitalopram

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

• esketamine intranasal

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

• estazolam

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

• estradiol

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

• estropipate

  Minor (1)estropipate, nortriptyline. 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)nortriptyline and ethanol both increase sedation. Use Caution/Monitor.

• ethinylestradiol

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

• eucalyptus

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

• ezogabine

  Monitor Closely (1)ezogabine, nortriptyline. 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 nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP2D6 substrates as necessary.

• fenfluramine

  Monitor Closely (3)fenfluramine, nortriptyline. 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.
  
  nortriptyline and fenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  nortriptyline increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline, 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 nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• fexinidazole

  Serious - Use Alternative (1)fexinidazole and nortriptyline 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 nortriptyline both increase QTc interval. Use Caution/Monitor.

• flavoxate

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

• flecainide

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

• fluconazole

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

• fluoxetine

  Monitor Closely (1)nortriptyline and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (2)fluoxetine and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.
  
  fluoxetine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• fluphenazine

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

• flurazepam

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

• fluvoxamine

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

• formoterol

  Monitor Closely (1)nortriptyline increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (2)nortriptyline and formoterol both increase QTc interval. Avoid or Use Alternate Drug.
  
  nortriptyline, 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 nortriptyline by decreasing metabolism. Avoid or Use Alternate Drug.

• foscarnet

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

• fostemsavir

  Monitor Closely (1)nortriptyline and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.

• frovatriptan

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

• gabapentin

  Monitor Closely (1)gabapentin, nortriptyline. 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, nortriptyline. 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 nortriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• ganaxolone

  Monitor Closely (1)nortriptyline and ganaxolone both increase sedation. Use Caution/Monitor.

• gemifloxacin

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

• gilteritinib

  Monitor Closely (1)gilteritinib and nortriptyline both increase QTc interval. Use Caution/Monitor.

• givosiran

  Serious - Use Alternative (1)givosiran will increase the level or effect of nortriptyline 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)nortriptyline increases effects of glimepiride by pharmacodynamic synergism. Minor/Significance Unknown.

• glipizide

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

• glyburide

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

• glycopyrrolate

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

• glycopyrrolate inhaled

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

• glycopyrronium tosylate topical

  Monitor Closely (1)glycopyrronium tosylate topical, nortriptyline. 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

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

• guanfacine

  Serious - Use Alternative (1)nortriptyline 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 nortriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)nortriptyline and haloperidol both increase QTc interval. Avoid or Use Alternate Drug.
  
  haloperidol will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• henbane

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

• homatropine

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

• huperzine A

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

• hydrocodone

  Monitor Closely (1)hydrocodone, nortriptyline. 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 nortriptyline both increase sedation. Use Caution/Monitor.

• hydroxychloroquine sulfate

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

• hydroxyprogesterone caproate

  Minor (1)hydroxyprogesterone caproate, nortriptyline. 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 (2)hydroxyzine and nortriptyline both increase QTc interval. Use Caution/Monitor.
  
  hydroxyzine and nortriptyline both increase sedation. Use Caution/Monitor.

• hyoscyamine

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

• hyoscyamine spray

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

• ibutilide

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

• iloperidone

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

• imatinib

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

• imipramine

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

• indacaterol, inhaled

  Monitor Closely (1)indacaterol, inhaled, nortriptyline. 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)nortriptyline and indapamide both increase QTc interval. Contraindicated.

• insulin aspart

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

• insulin detemir

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

• insulin glargine

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

• insulin glulisine

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

• insulin lispro

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

• insulin NPH

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

• insulin regular human

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

• iobenguane I 123

  Contraindicated (1)nortriptyline 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)nortriptyline 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 nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor. Due to the poor systemic absorption of ipratropium, interaction unlikely at regularly recommended dosages.

• isocarboxazid

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

• isoflurane

  Monitor Closely (1)isoflurane and nortriptyline both increase QTc interval. Use Caution/Monitor.

• isoniazid

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

• isoproterenol

  Monitor Closely (1)nortriptyline increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline, 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, nortriptyline. Mechanism: unknown. Minor/Significance Unknown. Risk of cardiac arrhythmias.

• itraconazole

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

• ivosidenib

  Serious - Use Alternative (1)ivosidenib and nortriptyline 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 nortriptyline both increase sedation. Use Caution/Monitor.Minor (1)ketamine, nortriptyline. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Risk of arrhythmias or hypotension.

• ketoconazole

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

• ketotifen, ophthalmic

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

• L-tryptophan

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

• lapatinib

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

• lasmiditan

  Monitor Closely (2)lasmiditan, nortriptyline. 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.
  
  nortriptyline increases effects of lasmiditan by serotonin levels. Use Caution/Monitor. Coadministration may increase risk of serotonin syndrome.

• lefamulin

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

• lemborexant

  Monitor Closely (1)lemborexant, nortriptyline. 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)nortriptyline increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline, 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)nortriptyline and levofloxacin both increase QTc interval. Modify Therapy/Monitor Closely.

• levoketoconazole

  Monitor Closely (1)levoketoconazole will increase the level or effect of nortriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline and levoketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• levomilnacipran

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

• levorphanol

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

• linezolid

  Serious - Use Alternative (1)linezolid and nortriptyline 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)nortriptyline, 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).
  
  nortriptyline increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline, 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 (2)lithium and nortriptyline both increase QTc interval. Use Caution/Monitor.
  
  nortriptyline and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)lithium, nortriptyline. Other (see comment). Minor/Significance Unknown. Comment: Risk of neurotoxicity in geriatric pts. Multiple mechanisms involved.

• lofepramine

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

• lofexidine

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

• loprazolam

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

• lorazepam

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

• lorcaserin

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

• lormetazepam

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

• loxapine

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

• loxapine inhaled

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

• lsd

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

• lumefantrine

  Serious - Use Alternative (2)nortriptyline and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.
  
  lumefantrine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• lurasidone

  Monitor Closely (1)lurasidone increases effects of nortriptyline by Other (see comment). Use Caution/Monitor. Comment: Potential for additive CNS effects .

• macimorelin

  Serious - Use Alternative (1)macimorelin and nortriptyline 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 nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  maprotiline and nortriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)maprotiline and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.
  
  maprotiline and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• maraviroc

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

• marijuana

  Monitor Closely (2)marijuana will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  nortriptyline and marijuana both increase sedation. Use Caution/Monitor.

• meclizine

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

• mefloquine

  Serious - Use Alternative (1)mefloquine increases toxicity of nortriptyline 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)nortriptyline and melatonin both increase sedation. Use Caution/Monitor.

• meperidine

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

• meprobamate

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

• mestranol

  Minor (1)mestranol, nortriptyline. 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)nortriptyline increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline, 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 nortriptyline both increase sedation. Use Caution/Monitor.

• metformin

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

• methadone

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

• methamphetamine

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

• methscopolamine

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

• methylene blue

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

• methylphenidate transdermal

  Monitor Closely (1)methylphenidate transdermal will increase the level or effect of nortriptyline by decreasing elimination. Modify Therapy/Monitor Closely. Consider decreasing the dose of these drugs when given coadministered with methylphenidate. Monitor for drug toxiticities when initiating or discontinuing methylphenidate.

• metoclopramide intranasal

  Serious - Use Alternative (1)nortriptyline, 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 nortriptyline both increase sedation. Use Caution/Monitor.

• midazolam intranasal

  Monitor Closely (1)midazolam intranasal, nortriptyline. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

• midodrine

  Monitor Closely (1)nortriptyline increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline, 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, nortriptyline. QTc interval. Modify Therapy/Monitor Closely. Use alternatives if available.

• miglitol

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

• milnacipran

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

• mirabegron

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

• mirtazapine

  Monitor Closely (2)nortriptyline and mirtazapine both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  nortriptyline and mirtazapine both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)mirtazapine and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• mobocertinib

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

• morphine

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

• motherwort

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

• moxifloxacin

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

• moxonidine

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

• nabilone

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

• nalbuphine

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

• naratriptan

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

• nateglinide

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

• nefazodone

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

• nefopam

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

• neostigmine

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

• netupitant/palonosetron

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

• nilotinib

  Monitor Closely (1)nilotinib will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.

• norepinephrine

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

• octreotide

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

• octreotide (Antidote)

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

• ofloxacin

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

• olanzapine

  Monitor Closely (2)olanzapine and nortriptyline both increase QTc interval. Use Caution/Monitor.
  
  olanzapine and nortriptyline both increase sedation. Use Caution/Monitor.

• oliceridine

  Monitor Closely (2)nortriptyline, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely.
  
  nortriptyline 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)nortriptyline 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

• olopatadine intranasal

  Serious - Use Alternative (1)nortriptyline and olopatadine intranasal both increase sedation. Avoid or Use Alternate Drug. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

• onabotulinumtoxinA

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

• ondansetron

  Serious - Use Alternative (2)nortriptyline 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, nortriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.

• opium tincture

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

• orphenadrine

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

• osilodrostat

  Monitor Closely (1)osilodrostat and nortriptyline both increase QTc interval. Use Caution/Monitor.

• osimertinib

  Monitor Closely (1)osimertinib and nortriptyline 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 nortriptyline both increase sedation. Use Caution/Monitor.

• oxybutynin

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

• oxybutynin topical

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

• oxybutynin transdermal

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

• oxycodone

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

• oxymetazoline intranasal

  Monitor Closely (1)nortriptyline 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 nortriptyline both increase sedation. Use Caution/Monitor.

• ozanimod

  Monitor Closely (1)ozanimod and nortriptyline 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 nortriptyline 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)nortriptyline and paliperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  paliperidone and nortriptyline both increase sedation. Use Caution/Monitor.

• palonosetron

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

• panax ginseng

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

• pancuronium

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

• papaveretum

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

• papaverine

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

• parecoxib

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

• paroxetine

  Monitor Closely (1)nortriptyline and paroxetine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (2)paroxetine and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.
  
  paroxetine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• pasireotide

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

• pazopanib

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

• peginterferon alfa 2b

  Monitor Closely (1)peginterferon alfa 2b, nortriptyline. 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)nortriptyline and pentamidine both increase QTc interval. Contraindicated.

• pentazocine

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

• pentobarbital

  Monitor Closely (1)pentobarbital and nortriptyline both increase sedation. Use Caution/Monitor.Minor (1)pentobarbital, nortriptyline. 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 (2)perphenazine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  perphenazine and nortriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)nortriptyline, perphenazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  nortriptyline, perphenazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• phendimetrazine

  Monitor Closely (1)nortriptyline increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline, 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 nortriptyline both increase serotonin levels. Contraindicated.

• phenobarbital

  Monitor Closely (1)phenobarbital and nortriptyline both increase sedation. Use Caution/Monitor.Minor (1)phenobarbital, nortriptyline. 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)nortriptyline increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline, 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)nortriptyline increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline, 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)nortriptyline, 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)nortriptyline increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .Serious - Use Alternative (1)nortriptyline, 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)nortriptyline and pholcodine both increase sedation. Use Caution/Monitor.

• physostigmine

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

• pilocarpine

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

• pimozide

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

• pioglitazone

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

• pirbuterol

  Monitor Closely (1)nortriptyline increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline, 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)nortriptyline 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 nortriptyline by unspecified interaction mechanism. Minor/Significance Unknown. Theoretical interaction.

• posaconazole

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

• pralidoxime

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

• pregabalin

  Monitor Closely (1)pregabalin, nortriptyline. 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 nortriptyline both increase sedation. Use Caution/Monitor.Minor (1)primidone, nortriptyline. 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)nortriptyline and procainamide both increase QTc interval. Contraindicated.

• procarbazine

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

• prochlorperazine

  Monitor Closely (2)prochlorperazine and nortriptyline both increase QTc interval. Use Caution/Monitor.
  
  prochlorperazine and nortriptyline both increase sedation. Use Caution/Monitor.Minor (2)nortriptyline, prochlorperazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  nortriptyline, prochlorperazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• progesterone micronized

  Minor (1)progesterone micronized, nortriptyline. 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 nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)nortriptyline, promazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  nortriptyline, promazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• promethazine

  Monitor Closely (2)promethazine and nortriptyline both increase QTc interval. Use Caution/Monitor.
  
  promethazine and nortriptyline both increase sedation. Use Caution/Monitor.Minor (2)nortriptyline, promethazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  nortriptyline, promethazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• propafenone

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

• propantheline

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

• propofol

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

• propylhexedrine

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

• protriptyline

  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.

• pseudoephedrine

  Serious - Use Alternative (1)nortriptyline 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 nortriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• quazepam

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

• quetiapine

  Monitor Closely (2)quetiapine and nortriptyline both increase sedation. Use Caution/Monitor.
  
  quetiapine, nortriptyline. 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.

• quinacrine

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

• quinidine

  Contraindicated (1)quinidine and nortriptyline both increase QTc interval. Contraindicated.Serious - Use Alternative (1)quinidine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• quinine

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

• ramelteon

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

• ranolazine

  Monitor Closely (2)ranolazine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.
  
  nortriptyline and ranolazine both increase QTc interval. Modify Therapy/Monitor Closely.

• rapacuronium

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

• rasagiline

  Serious - Use Alternative (1)rasagiline and nortriptyline 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, nortriptyline. 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)nortriptyline increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• ribociclib

  Serious - Use Alternative (2)ribociclib will increase the level or effect of nortriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  ribociclib increases toxicity of nortriptyline by QTc interval. Avoid or Use Alternate Drug.

• rifabutin

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

• rifampin

  Minor (1)rifampin decreases levels of nortriptyline by increasing metabolism. Minor/Significance Unknown.

• rilpivirine

  Monitor Closely (1)rilpivirine increases toxicity of nortriptyline 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)nortriptyline and risperidone both increase QTc interval. Modify Therapy/Monitor Closely.
  
  risperidone and nortriptyline both increase sedation. Use Caution/Monitor.

• ritonavir

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

• rizatriptan

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

• rocuronium

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

• romidepsin

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

• rosiglitazone

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

• safinamide

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

• sage

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

• salmeterol

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

• saxagliptin

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

• scopolamine

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

• scullcap

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

• secobarbital

  Monitor Closely (1)secobarbital and nortriptyline both increase sedation. Use Caution/Monitor.Minor (1)secobarbital, nortriptyline. 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 nortriptyline 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 nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• selinexor

  Serious - Use Alternative (1)selinexor, nortriptyline. 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 nortriptyline by QTc interval. Use Caution/Monitor.

• serdexmethylphenidate/dexmethylphenidate

  Serious - Use Alternative (1)nortriptyline, serdexmethylphenidate/dexmethylphenidate. Other (see comment). Avoid or Use Alternate Drug. Comment: Tricyclic antidepressants increase or decrease effects of sympathomimetics, by blocking reuptake of NE, or blocking uptake of indirect sympathomimetics into the adrenergic neuron.Minor (1)serdexmethylphenidate/dexmethylphenidate increases effects of nortriptyline by decreasing metabolism. Minor/Significance Unknown.

• sertraline

  Monitor Closely (1)sertraline will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely.Serious - Use Alternative (2)sertraline and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.
  
  sertraline and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• sevoflurane

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

• shepherd's purse

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

• sitagliptin

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

• sodium oxybate

  Serious - Use Alternative (1)nortriptyline, 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 nortriptyline 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 nortriptyline 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)nortriptyline, 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 (2)solifenacin and nortriptyline both increase QTc interval. Use Caution/Monitor.
  
  solifenacin and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• sorafenib

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

• sotalol

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

• St John's Wort

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

• stiripentol

  Monitor Closely (1)stiripentol, nortriptyline. 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 nortriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• sufentanil

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

• sufentanil SL

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

• sumatriptan

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

• sumatriptan intranasal

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

• suvorexant

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

• tacrolimus

  Monitor Closely (1)tacrolimus and nortriptyline both increase QTc interval. Use Caution/Monitor.

• tapentadol

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

• tedizolid

  Serious - Use Alternative (1)tedizolid, nortriptyline. 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)nortriptyline and telavancin both increase QTc interval. Modify Therapy/Monitor Closely.

• temazepam

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

• terbutaline

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

  Contraindicated (1)thioridazine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Contraindicated.Monitor Closely (1)thioridazine and nortriptyline both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)thioridazine and nortriptyline both increase QTc interval. Avoid or Use Alternate Drug.Minor (2)nortriptyline, thioridazine. Either increases levels of the other by decreasing metabolism. Minor/Significance Unknown. Additive anticholinergic effects.
  
  nortriptyline, thioridazine. Either increases levels of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

• thiothixene

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

• tiotropium

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

• tipranavir

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

• tolazamide

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

• tolbutamide

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

• tolterodine

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

• topiramate

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

• toremifene

  Serious - Use Alternative (1)nortriptyline and toremifene both increase QTc interval. Avoid or Use Alternate Drug. Concurrent use of toremifene with agents causing QT prolongation should be avoided. If concomitant use is required it's recommended that toremifene be interrupted. If interruption not possible, patients requiring therapy with a drug that prolongs QT should be closely monitored. ECGs should be obtained for high risk patients.

• tramadol

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

• tranylcypromine

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

• trazodone

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

• triazolam

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

• triclofos

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

• trifluoperazine

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

• trihexyphenidyl

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

• trimethoprim

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

• trimipramine

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

• triprolidine

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

• tropisetron

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

• trospium chloride

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

• umeclidinium bromide/vilanterol inhaled

  Serious - Use Alternative (2)nortriptyline 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.
  
  nortriptyline 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

• valbenazine

  Monitor Closely (1)valbenazine and nortriptyline both increase QTc interval. Use Caution/Monitor.

• valerian

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

• vandetanib

  Serious - Use Alternative (1)nortriptyline, 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)nortriptyline increases effects of vasopressin by pharmacodynamic synergism. Minor/Significance Unknown.

• vecuronium

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

• vemurafenib

  Serious - Use Alternative (1)vemurafenib and nortriptyline 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)nortriptyline and venlafaxine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (2)venlafaxine and nortriptyline both increase serotonin levels. Avoid or Use Alternate Drug.
  
  venlafaxine will increase the level or effect of nortriptyline by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

• verapamil

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

• vilanterol/fluticasone furoate inhaled

  Serious - Use Alternative (2)nortriptyline 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
  
  nortriptyline 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)nortriptyline, 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)nortriptyline increases effects of vildagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

• voclosporin

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

• voriconazole

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

• vortioxetine

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

• xylometazoline

  Monitor Closely (1)nortriptyline increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)nortriptyline, 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, nortriptyline. Mechanism: unspecified interaction mechanism. Contraindicated. May cause increase or decrease in blood pressure.

• yohimbine

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

• ziprasidone

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

• zolmitriptan

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

• zolpidem

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