amitriptyline (Rx)

Depression

Outpatient: 25-50 mg PO qHS initially; increase by 25 mg every 5-7 days to 100-200 mg/day (may divide doses throughout day or give at bedtime); if needed, may increase to 300 mg/day

Inpatient: 100-300 mg PO qDay

Postherpetic Neuralgia (Off-label)

65-100 mg PO qDay for at least 3 weeks

Migraine Prophylaxis (Off-label)

10-25 mg PO qHS; 10-400 mg PO qHS dose range

Eating Disorder (Off-label)

150 mg PO qHS for 8 weeks

Depression

Adolescents

• Initial: 25-50 mg/day PO in divided doses
• Increase gradually to 100 mg/day in divided doses

Children (Off-label)

• First 3 days: 1 mg/kg/day divided q8hr PO, THEN  
• 1.5 mg/kg/day divided q8hr PO

Analgesia for Chronic Pain (Off-label)

Load: 0.1 mg/kg PO qHS; may increase as tolerated over 2-3 weeks  

Maintenance: 0.5-2 mg/kg PO qHS

Migraine Prophylaxis (Off-label)

0.25 mg/kg/day PO qHS; may increase dose by 0.25 mg/kg/day; not to exceed 1 mg/kg/day  

Dose range: 0.1-2 mg/kg/day; not to exceed 2 mg/kg/day or 75 mg/day; if dose >1 mg/kg/day, divide dose q12hr

Depression

10-25 mg PO qHS; may increase by 10-25 mg increments qWeek if needed and as tolerated

Dosage range: 25-150 mg/day

Dosing Considerations

Avoid; strong anticholinergic and sedative effects; may cause orthostatic hypotension (Beers criteria)

Consider alternatives; if must use, initiate with lower initial dose

Contraindicated (16)

• disopyramide

  amitriptyline and disopyramide both increase QTc interval. Contraindicated.

• dronedarone

  dronedarone will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  dronedarone will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Contraindicated.

• ibutilide

  amitriptyline and ibutilide both increase QTc interval. Contraindicated.

• indapamide

  amitriptyline and indapamide both increase QTc interval. Contraindicated.

• iobenguane I 123

  amitriptyline 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 amitriptyline both increase serotonin levels. Contraindicated.

• pentamidine

  amitriptyline and pentamidine both increase QTc interval. Contraindicated.

• phenelzine

  phenelzine and amitriptyline both increase serotonin levels. Contraindicated.

• pimozide

  amitriptyline and pimozide both increase QTc interval. Contraindicated.

• procainamide

  amitriptyline and procainamide both increase QTc interval. Contraindicated.

• procarbazine

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

• quinidine

  quinidine and amitriptyline both increase QTc interval. Contraindicated.

• safinamide

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

• selegiline

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

• sotalol

  amitriptyline and sotalol both increase QTc interval. Contraindicated.

• tranylcypromine

  tranylcypromine and amitriptyline both increase serotonin levels. Contraindicated.

Serious - Use Alternative (137)

• albuterol

  amitriptyline, 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

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

• amoxapine

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

• arformoterol

  amitriptyline, 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

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

• artemether

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

• artemether/lumefantrine

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

• benzphetamine

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

• buspirone

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

• calcium/magnesium/potassium/sodium oxybates

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

• citalopram

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

• clarithromycin

  clarithromycin will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  amitriptyline and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug.

• clomipramine

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

• clonidine

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

• cyclobenzaprine

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

• dacomitinib

  dacomitinib will increase the level or effect of amitriptyline 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.

• dasatinib

  dasatinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• desipramine

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

• desvenlafaxine

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

• dexfenfluramine

  amitriptyline, 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

  amitriptyline, 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

  amitriptyline, 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

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

• diethylpropion

  amitriptyline, 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

  amitriptyline, 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

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

• dolasetron

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

• dopamine

  amitriptyline, 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

  amitriptyline, 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.

• dosulepin

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

• doxepin

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

• dronedarone

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

• droperidol

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

• duloxetine

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

• encorafenib

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

• ephedrine

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

  erythromycin base will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  erythromycin base will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
  
  amitriptyline and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  erythromycin ethylsuccinate will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  erythromycin ethylsuccinate will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
  
  amitriptyline and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  erythromycin lactobionate will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  erythromycin lactobionate will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
  
  amitriptyline and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.

• erythromycin stearate

  erythromycin stearate will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  erythromycin stearate will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
  
  amitriptyline and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.

• escitalopram

  escitalopram and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.
  
  escitalopram increases toxicity of amitriptyline by QTc interval. Avoid or Use Alternate Drug.

• fenfluramine

  amitriptyline, 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 amitriptyline 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

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

• fluoxetine

  fluoxetine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug.
  
  fluoxetine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• fluphenazine

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

• fluvoxamine

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

• formoterol

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

• givosiran

  givosiran will increase the level or effect of amitriptyline 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, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.
  
  granisetron and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• guanfacine

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

• haloperidol

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

• hydroxychloroquine sulfate

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

• imipramine

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

• iobenguane I 131

  amitriptyline 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

  amitriptyline, 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.

• ivosidenib

  ivosidenib and amitriptyline 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

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

• lasmiditan

  lasmiditan increases effects of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• lefamulin

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

• levalbuterol

  amitriptyline, 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

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

• levomilnacipran

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

• linezolid

  linezolid and amitriptyline 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

  amitriptyline, 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

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

• lorcaserin

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

• lumefantrine

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

• macimorelin

  macimorelin and amitriptyline 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

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

• mefloquine

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

• meperidine

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

• metaproterenol

  amitriptyline, 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

  amitriptyline, 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 amitriptyline 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

  amitriptyline, 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

  amitriptyline, 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

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

• mirtazapine

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

• mobocertinib

  mobocertinib will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently

• moxifloxacin

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

• nefazodone

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

• netupitant/palonosetron

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

• nilotinib

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

• norepinephrine

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

• nortriptyline

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

• octreotide

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

• octreotide (Antidote)

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

• ondansetron

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

• ozanimod

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

• paroxetine

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

• perphenazine

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

• phendimetrazine

  amitriptyline, 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

  amitriptyline, 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

  amitriptyline, 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

  amitriptyline, 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

  amitriptyline, 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

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

• propylhexedrine

  amitriptyline, 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

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

• pseudoephedrine

  amitriptyline 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 amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• ranolazine

  ranolazine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• rasagiline

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

• ribociclib

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

• salmeterol

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

• selinexor

  selinexor, amitriptyline. 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

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

• sodium oxybate

  amitriptyline, 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

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

• tedizolid

  tedizolid, amitriptyline. 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

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

• toremifene

  amitriptyline 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

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

• trifluoperazine

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

• trimipramine

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

• umeclidinium bromide/vilanterol inhaled

  amitriptyline 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.
  
  amitriptyline 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

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

• venlafaxine

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

• vilanterol/fluticasone furoate inhaled

  amitriptyline 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
  
  amitriptyline 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

  amitriptyline, 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

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

• xylometazoline

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

• yohimbine

  amitriptyline, 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

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

Monitor Closely (390)

• 5-HTP

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

• abiraterone

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

• albuterol

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

• alfentanil

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

• alfuzosin

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

• almotriptan

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

• alprazolam

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

• amifampridine

  amitriptyline 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 amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• amisulpride

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

• amobarbital

  amobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  amobarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  amobarbital and amitriptyline both increase sedation. Use Caution/Monitor.
  
  amobarbital, amitriptyline. Other (see comment). Use Caution/Monitor. 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

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

• anticholinergic/sedative combos

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

• apomorphine

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

• aprepitant

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

• arformoterol

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

• aripiprazole

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

• armodafinil

  armodafinil will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  amitriptyline increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• atazanavir

  atazanavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  atazanavir increases levels of amitriptyline by unspecified interaction mechanism. Use Caution/Monitor.

• atomoxetine

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

• atorvastatin

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

• atracurium

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

• atropine

  atropine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• atropine IV/IM

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

• azelastine

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

• azithromycin

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

• baclofen

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

• bedaquiline

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

• belladonna alkaloids

  belladonna alkaloids and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• belladonna and opium

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

• benperidol

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

• benzhydrocodone/acetaminophen

  benzhydrocodone/acetaminophen, amitriptyline. 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

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

• benztropine

  benztropine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely. Additive anticholinergic adverse effects may be seen with concurrent use.

• bethanechol

  bethanechol increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• brompheniramine

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

• buprenorphine

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

• buprenorphine buccal

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

• buprenorphine subdermal implant

  amitriptyline, 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

  amitriptyline, 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

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

• butabarbital

  butabarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  butabarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  butabarbital and amitriptyline both increase sedation. Use Caution/Monitor.

• butalbital

  butalbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  butalbital and amitriptyline both increase sedation. Use Caution/Monitor.

• butorphanol

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

• caffeine

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

• carbachol

  carbachol increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• carbamazepine

  carbamazepine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• carbinoxamine

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

• carisoprodol

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

• cenobamate

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

• ceritinib

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

• cevimeline

  cevimeline increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• chloral hydrate

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

• chlordiazepoxide

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

• chloroquine

  chloroquine increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor.

• chlorpheniramine

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

• chlorpromazine

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

• chlorzoxazone

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

• cimetidine

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

• cinnarizine

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

• cisatracurium

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

• clarithromycin

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

• clemastine

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

• clobazam

  clobazam will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Lower doses of drugs metabolized by CYP2D6 may be required when used concomitantly.
  
  amitriptyline, 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

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

• clonazepam

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

• clorazepate

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

• clotrimazole

  clotrimazole will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• clozapine

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

• cobicistat

  cobicistat will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Carefully titrate antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant response
  
  cobicistat will increase the level or effect of amitriptyline 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

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

• codeine

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

• conivaptan

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

• crizotinib

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

• cyclizine

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

• cyclobenzaprine

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

• cyclosporine

  cyclosporine will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  cyclosporine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• cyproheptadine

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

• dantrolene

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

• daridorexant

  amitriptyline 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 amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  darifenacin and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• darunavir

  darunavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with SSRIs, TCAs, or trazodone may require dose titration of antidepressant to desired effect (eg, using the lowest feasible initial or maintenance dose). Monitor for antidepressant response.

• dasatinib

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

• debrisoquine

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

• degarelix

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

• desflurane

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

• desipramine

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

• deutetrabenazine

  amitriptyline and deutetrabenazine both increase sedation. Use Caution/Monitor.
  
  deutetrabenazine and amitriptyline both increase QTc interval. Use Caution/Monitor.

• dexchlorpheniramine

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

• dexfenfluramine

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

• dexmedetomidine

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

• dexmethylphenidate

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

• dextroamphetamine

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

• dextroamphetamine transdermal

  amitriptyline 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 amitriptyline both increase sedation. Use Caution/Monitor.

• diamorphine

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

• diazepam

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

• diazepam intranasal

  diazepam intranasal, amitriptyline. 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 amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• diethylpropion

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

• difelikefalin

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

• difenoxin hcl

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

• dihydroergotamine

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

• dihydroergotamine intranasal

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

• diltiazem

  diltiazem will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use with amitriptyline may alter blood pressure control.

• dimenhydrinate

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

• diphenhydramine

  diphenhydramine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.
  
  diphenhydramine and amitriptyline both increase sedation. Use Caution/Monitor.

• diphenoxylate hcl

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

• dipipanone

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

• dobutamine

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

• dofetilide

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

• dolasetron

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

• donepezil

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

• dopamine

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

• dopexamine

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

• dosulepin

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

• doxepin

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

• doxylamine

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

• droperidol

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

• echothiophate iodide

  echothiophate iodide increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• efavirenz

  efavirenz will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  efavirenz will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  efavirenz and amitriptyline both increase QTc interval. Use Caution/Monitor.

• elagolix

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

• eletriptan

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

• eliglustat

  eliglustat increases levels of amitriptyline 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 increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

• entrectinib

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

• ephedrine

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

• epinephrine

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

• epinephrine inhaled

  amitriptyline 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

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

• ergotamine

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

• eribulin

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

• esketamine intranasal

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

• eslicarbazepine acetate

  eslicarbazepine acetate will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• esomeprazole

  esomeprazole will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• estazolam

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

• ethanol

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

• etomidate

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

• etravirine

  etravirine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• ezogabine

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

• felbamate

  felbamate will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• felodipine

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

• fenfluramine

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

• fingolimod

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

• flavoxate

  flavoxate and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• flecainide

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

• fluconazole

  fluconazole will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  fluconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fluoxetine

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

• fluphenazine

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

• flurazepam

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

• fluvoxamine

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

• formoterol

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

• fosamprenavir

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

• foscarnet

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

• fosphenytoin

  fosphenytoin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  fosphenytoin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• fostemsavir

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

• frovatriptan

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

• gabapentin

  gabapentin, amitriptyline. 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, amitriptyline. 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 amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• ganaxolone

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

• gemifloxacin

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

• gilteritinib

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

• glecaprevir/pibrentasvir

  glecaprevir/pibrentasvir will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

• glycopyrrolate

  glycopyrrolate and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.
  
  amitriptyline increases levels of glycopyrrolate by unknown mechanism. Use Caution/Monitor.

• glycopyrrolate inhaled

  glycopyrrolate inhaled and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.
  
  amitriptyline increases levels of glycopyrrolate inhaled by unknown mechanism. Use Caution/Monitor.

• glycopyrronium tosylate topical

  glycopyrronium tosylate topical, amitriptyline. 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.

• grapefruit

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

• haloperidol

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

• henbane

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

• homatropine

  homatropine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• huperzine A

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

• hydrocodone

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

• hydroxyzine

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

• hyoscyamine

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

• hyoscyamine spray

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

• iloperidone

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

• imipramine

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

• indacaterol, inhaled

  indacaterol, inhaled, amitriptyline. 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.

• indinavir

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

• ipratropium

  ipratropium and amitriptyline 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 amitriptyline both increase QTc interval. Use Caution/Monitor.

• isoniazid

  isoniazid will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  amitriptyline and isoniazid both increase serotonin levels. Modify Therapy/Monitor Closely.

• isoproterenol

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

• istradefylline

  istradefylline will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

• itraconazole

  itraconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  itraconazole and amitriptyline both increase QTc interval. Use Caution/Monitor.

• ivacaftor

  ivacaftor increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

• ketamine

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

• ketoconazole

  ketoconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• ketotifen, ophthalmic

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

• L-tryptophan

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

• lapatinib

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

• lasmiditan

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

• lemborexant

  lemborexant, amitriptyline. 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.

• letermovir

  letermovir increases levels of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levalbuterol

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

• levofloxacin

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

• levoketoconazole

  levoketoconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  levoketoconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• levorphanol

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

• lisdexamfetamine

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

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

• lofepramine

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

• lofexidine

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

• loprazolam

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

• loratadine

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

• lorazepam

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

• lorcaserin

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

• lormetazepam

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

• loxapine

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

• loxapine inhaled

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

• lsd

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

• lurasidone

  lurasidone increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of hypotension with concurrent use. Monitor blood pressure and adjust dose of antihypertensive agent as needed.
  
  lurasidone, amitriptyline. Either increases toxicity of the other by sedation. Use Caution/Monitor. Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

• maprotiline

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

• maraviroc

  maraviroc, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.

• marijuana

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

• mavacamten

  amitriptyline will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

• meclizine

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

• melatonin

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

• meperidine

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

• meprobamate

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

• metaproterenol

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

• metaxalone

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

• methadone

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

• methamphetamine

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

• methocarbamol

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

• methscopolamine

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

• methylenedioxymethamphetamine

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

• methylphenidate

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

• midazolam

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

• midazolam intranasal

  midazolam intranasal, amitriptyline. Either increases effects 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

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

• mifepristone

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

• mipomersen

  mipomersen, amitriptyline. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

• mirabegron

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

• mirtazapine

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

• modafinil

  modafinil will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  amitriptyline increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• morphine

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

• motherwort

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

• moxonidine

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

• nabilone

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

• nalbuphine

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

• naratriptan

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

• nefazodone

  nefazodone will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  nefazodone will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• nefopam

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

• nelfinavir

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

• neostigmine

  neostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• nicardipine

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

• nifedipine

  nifedipine will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• norepinephrine

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

• nortriptyline

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

• ofloxacin

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

• olanzapine

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

• oliceridine

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

  amitriptyline 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 amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• opium tincture

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

• orphenadrine

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

• osilodrostat

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

• osimertinib

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

• oxaliplatin

  oxaliplatin will increase the level or effect of amitriptyline by Other (see comment). Use Caution/Monitor. Monitor for ECG changes if therapy is initiated in patients with drugs known to prolong QT interval.

• oxazepam

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

• oxybutynin

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

• oxybutynin topical

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

• oxybutynin transdermal

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

• oxycodone

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

• oxymetazoline intranasal

  amitriptyline 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 amitriptyline both increase sedation. Use Caution/Monitor.

• ozanimod

  ozanimod and amitriptyline 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

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

• pancuronium

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

• papaveretum

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

• papaverine

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

• paroxetine

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

• pasireotide

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

• pazopanib

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

• peginterferon alfa 2b

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

• pentobarbital

  pentobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  pentobarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  pentobarbital and amitriptyline both increase sedation. Use Caution/Monitor.

• perphenazine

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

• phendimetrazine

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

• phenobarbital

  phenobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  phenobarbital will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  phenobarbital and amitriptyline both increase sedation. Use Caution/Monitor.

• phentermine

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

• phenylephrine

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

• phenylephrine ophthalmic

  amitriptyline, 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

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

• phenytoin

  phenytoin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor therapeutic efficacy of amitriptyline; an increased dose may be required. Serum phenytoin levels should be obtained when tricyclic antidepressant agents are added to therapy due to the potential for impaired phenytoin metabolism and decreased seizure threshold. Tricyclic antidepressants when given concomitantly with anticonvulsants can increase CNS depression.
  
  phenytoin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor therapeutic efficacy of amitriptyline; an increased dose may be required. Serum phenytoin levels should be obtained when tricyclic antidepressant agents are added to therapy due to the potential for impaired phenytoin metabolism and decreased seizure threshold. Tricyclic antidepressants when given concomitantly with anticonvulsants can increase CNS depression.

• pholcodine

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

• physostigmine

  physostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• pilocarpine

  pilocarpine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• pimozide

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

• pirbuterol

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

• ponatinib

  ponatinib increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• posaconazole

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

• pralidoxime

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

• pregabalin

  pregabalin, amitriptyline. 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 will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  primidone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  primidone and amitriptyline both increase sedation. Use Caution/Monitor.

• prochlorperazine

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

• promethazine

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

• propantheline

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

• propofol

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

• propylhexedrine

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

• protriptyline

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

• pyridostigmine

  pyridostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• quazepam

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

• quercetin

  quercetin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• quetiapine

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

• quinine

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

• ramelteon

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

• ranolazine

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

• rapacuronium

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

• remifentanil

  amitriptyline, remifentanil. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. May also increase risk of serotonin syndrome.

• remimazolam

  remimazolam, amitriptyline. 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 will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  rifabutin decreases levels of amitriptyline by increasing metabolism. Use Caution/Monitor.

• rifampin

  rifampin will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  rifampin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  rifampin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• rifapentine

  rifapentine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rilpivirine

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

• risperidone

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

• ritonavir

  ritonavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ritonavir will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• rivastigmine

  rivastigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• rizatriptan

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

• rocuronium

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

• rolapitant

  rolapitant will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.

• romidepsin

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

• salmeterol

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

• SAMe

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

• sarecycline

  sarecycline will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

• scopolamine

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

• scullcap

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

• secobarbital

  secobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  secobarbital and amitriptyline both increase sedation. Use Caution/Monitor.

• selpercatinib

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

• sevoflurane

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

• shepherd's purse

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

• simvastatin

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

• sirolimus

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

• sodium sulfate/?magnesium sulfate/potassium chloride

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

  amitriptyline, 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 amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

• sorafenib

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

• St John's Wort

  St John's Wort will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  St John's Wort will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• stiripentol

  stiripentol, amitriptyline. 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 amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• sufentanil

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

• sufentanil SL

  sufentanil SL, amitriptyline. 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

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

• sumatriptan

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

• sumatriptan intranasal

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

• suvorexant

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

• tacrolimus

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

• tapentadol

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

• telavancin

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

• temazepam

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

• terbinafine

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

• terbutaline

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

• teriflunomide

  teriflunomide decreases levels of amitriptyline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• thioridazine

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

• thiothixene

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

• tiotropium

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

• tolterodine

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

• tolvaptan

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

• topiramate

  amitriptyline and topiramate both increase sedation. Modify Therapy/Monitor Closely.
  
  topiramate increases toxicity of amitriptyline by unspecified interaction mechanism. Use Caution/Monitor. Amitriptyline levels may increase; adjust dose based on clinical response and not on basis of plasma levels.

• tramadol

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

• trazodone

  trazodone will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  amitriptyline and trazodone both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  amitriptyline and trazodone both increase sedation. Use Caution/Monitor.

• triazolam

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

• triclofos

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

• trifluoperazine

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

• trihexyphenidyl

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

• trimethoprim

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

• trimipramine

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

• triprolidine

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

• tropisetron

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

• trospium chloride

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

• tucatinib

  tucatinib will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

• valerian

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

• vecuronium

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

• venlafaxine

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

• verapamil

  verapamil will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. The frequency and severity of amitriptyline adverse effects (sedation, anticholinergic effects and orthostatic hypotension) may be increased. Cardiac dysrhythmic effects may be additive.

• voclosporin

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

• voriconazole

  voriconazole will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  amitriptyline and voriconazole both increase QTc interval. Modify Therapy/Monitor Closely.

• warfarin

  amitriptyline increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.

• xylometazoline

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

• yohimbine

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

• ziconotide

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

• ziprasidone

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

• zolmitriptan

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

Minor (104)

• acarbose

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

• armodafinil

  armodafinil will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• artemether/lumefantrine

  artemether/lumefantrine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• atropine

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

• atropine IV/IM

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

• bazedoxifene/conjugated estrogens

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

• bortezomib

  bortezomib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• bosentan

  bosentan will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• brimonidine

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

• budesonide

  budesonide will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• butabarbital

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

• chlorpromazine

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

• chlorpropamide

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

• conjugated estrogens

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

• cortisone

  cortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• desflurane

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

• dexamethasone

  dexamethasone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dexmethylphenidate

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

• DHEA, herbal

  DHEA, herbal will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• eslicarbazepine acetate

  eslicarbazepine acetate will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• estradiol

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

• estropipate

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

• ethanol

  ethanol, amitriptyline. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive impairment of motor skills.

• ethinylestradiol

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

• etomidate

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

• etravirine

  etravirine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• eucalyptus

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

• felodipine

  felodipine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• fludrocortisone

  fludrocortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fluphenazine

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

• glimepiride

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

• glipizide

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

• glyburide

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

• griseofulvin

  griseofulvin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• hydrocortisone

  hydrocortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• hydroxyprogesterone caproate

  hydroxyprogesterone caproate, amitriptyline. 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

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

• insulin detemir

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

• insulin glargine

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

• insulin glulisine

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

• insulin lispro

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

• insulin NPH

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

• insulin regular human

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

• isoniazid

  isoniazid will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• isoproterenol

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

• itraconazole

  itraconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ketamine

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

• lapatinib

  lapatinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lithium

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

• lumefantrine

  lumefantrine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• marijuana

  marijuana will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• mestranol

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

• metformin

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

• methylprednisolone

  methylprednisolone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• metronidazole

  metronidazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• metyrapone

  amitriptyline decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown.

• miconazole vaginal

  miconazole vaginal will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• miglitol

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

• nateglinide

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

• nevirapine

  nevirapine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nifedipine

  nifedipine will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nilotinib

  nilotinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• oxcarbazepine

  oxcarbazepine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.
  
  oxcarbazepine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• panax ginseng

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

• parecoxib

  parecoxib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• pentobarbital

  pentobarbital, amitriptyline. 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

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

• phenobarbital

  phenobarbital, amitriptyline. 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

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

• pleurisy root

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

• posaconazole

  posaconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• prednisone

  prednisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• primidone

  primidone, amitriptyline. 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

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

• progesterone micronized

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

• promazine

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

• promethazine

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

• propofol

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

• quinupristin/dalfopristin

  quinupristin/dalfopristin will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• repaglinide

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

• rosiglitazone

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

• rufinamide

  rufinamide will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• sage

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

• saxagliptin

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

• secobarbital

  secobarbital, amitriptyline. 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 amitriptyline by decreasing metabolism. Minor/Significance Unknown.

• sevoflurane

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

• sitagliptin

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

• sulfamethoxazole

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

• thioridazine

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

• tolazamide

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

• tolbutamide

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

• trifluoperazine

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

• vasopressin

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

• verapamil

  verapamil will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  verapamil increases levels of amitriptyline by decreasing metabolism. Minor/Significance Unknown.

• vildagliptin

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

• voriconazole

  voriconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zafirlukast

  zafirlukast will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• zolpidem

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

• 5-HTP

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

• abiraterone

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

• aclidinium

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

• albuterol

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

• alfuzosin

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

• almotriptan

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

• alprazolam

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

• amifampridine

  Monitor Closely (1)amitriptyline 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 amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.

• amisulpride

  Monitor Closely (2)amitriptyline and amisulpride both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended if coadministered.
  
  amisulpride and amitriptyline both increase QTc interval. Use Caution/Monitor. ECG monitoring is recommended if coadministered.

• amobarbital

  Monitor Closely (4)amobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  amobarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  amobarbital, amitriptyline. Other (see comment). Use Caution/Monitor. 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.
  
  amobarbital and amitriptyline both increase sedation. Use Caution/Monitor.

• amoxapine

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

• anticholinergic/sedative combos

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

• apomorphine

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

• aprepitant

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

• arformoterol

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

• armodafinil

  Monitor Closely (2)armodafinil will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  amitriptyline increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Minor (1)armodafinil will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• arsenic trioxide

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

• artemether

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

• artemether/lumefantrine

  Serious - Use Alternative (1)amitriptyline and artemether/lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)artemether/lumefantrine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• atazanavir

  Monitor Closely (2)atazanavir increases levels of amitriptyline by unspecified interaction mechanism. Use Caution/Monitor.
  
  atazanavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• atomoxetine

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

• atorvastatin

  Monitor Closely (1)atorvastatin will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• atracurium

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

• atropine

  Monitor Closely (1)atropine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.Minor (1)amitriptyline increases levels of atropine by unknown mechanism. Minor/Significance Unknown.

• atropine IV/IM

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

• azelastine

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

• azithromycin

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

• baclofen

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

• bazedoxifene/conjugated estrogens

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

• belladonna alkaloids

  Monitor Closely (1)belladonna alkaloids and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• belladonna and opium

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

• benperidol

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

• benzhydrocodone/acetaminophen

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

• bethanechol

  Monitor Closely (1)bethanechol increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• bortezomib

  Minor (1)bortezomib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• bosentan

  Minor (1)bosentan will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• brimonidine

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

• brompheniramine

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

• budesonide

  Minor (1)budesonide will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• buprenorphine

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

• buprenorphine buccal

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

• buprenorphine subdermal implant

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

• buspirone

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

• butabarbital

  Monitor Closely (3)butabarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  butabarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  butabarbital and amitriptyline both increase sedation. Use Caution/Monitor.Minor (1)butabarbital, amitriptyline. 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 (3)butalbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  butalbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  butalbital and amitriptyline both increase sedation. Use Caution/Monitor.Minor (1)butalbital, amitriptyline. 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 amitriptyline both increase sedation. Use Caution/Monitor.

• caffeine

  Monitor Closely (1)amitriptyline 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)amitriptyline, 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 amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• carbamazepine

  Monitor Closely (1)carbamazepine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Minor (1)carbamazepine decreases levels of amitriptyline by increasing metabolism. Minor/Significance Unknown.

• carbinoxamine

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

• carisoprodol

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

• cenobamate

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

• ceritinib

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

• cevimeline

  Monitor Closely (1)cevimeline increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• chloral hydrate

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

• chlordiazepoxide

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

• chloroquine

  Monitor Closely (1)chloroquine increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor.

• chlorpheniramine

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

• chlorpromazine

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

• chlorpropamide

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

• chlorzoxazone

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

• cimetidine

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

• cinnarizine

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

• cisatracurium

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

• citalopram

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

• clarithromycin

  Monitor Closely (1)clarithromycin will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Serious - Use Alternative (2)amitriptyline and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug.
  
  clarithromycin will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• clemastine

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

• clobazam

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

• clonazepam

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

• clonidine

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

• clotrimazole

  Monitor Closely (1)clotrimazole will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• clozapine

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

• cobicistat

  Monitor Closely (2)cobicistat will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Carefully titrate antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitoring for antidepressant response
  
  cobicistat will increase the level or effect of amitriptyline by Other (see comment). Use Caution/Monitor. Carefully titrate dose of the antidepressant to the desired effect, including using the lowest feasible initial or maintenance dose, and monitor its response during coadministration with TCAs and cobicistat.

• cocaine

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

• codeine

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

• conivaptan

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

• conjugated estrogens

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

• cortisone

  Minor (1)cortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• crizotinib

  Monitor Closely (1)crizotinib and amitriptyline 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 amitriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  cyclizine and amitriptyline both increase sedation. Use Caution/Monitor.

• cyclobenzaprine

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

• cyclosporine

  Monitor Closely (2)cyclosporine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  cyclosporine will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• cyproheptadine

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

• dacomitinib

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

• daridorexant

  Monitor Closely (1)amitriptyline 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 and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.
  
  darifenacin will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• darunavir

  Monitor Closely (1)darunavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration with SSRIs, TCAs, or trazodone may require dose titration of antidepressant to desired effect (eg, using the lowest feasible initial or maintenance dose). Monitor for antidepressant response.

• dasatinib

  Monitor Closely (1)amitriptyline and dasatinib both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)dasatinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

• debrisoquine

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

• degarelix

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

• desflurane

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

• desipramine

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

• desvenlafaxine

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

• deutetrabenazine

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

• dexamethasone

  Minor (1)dexamethasone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• dexchlorpheniramine

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

• dexfenfluramine

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

• dexmethylphenidate

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

• dextroamphetamine

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

• dextromoramide

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

• DHEA, herbal

  Minor (1)DHEA, herbal will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• diamorphine

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

• diazepam

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

• diazepam intranasal

  Monitor Closely (1)diazepam intranasal, amitriptyline. 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 amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• diethylpropion

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

• difenoxin hcl

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

• dihydroergotamine

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

• dihydroergotamine intranasal

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

• diltiazem

  Monitor Closely (1)diltiazem will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Concomitant use with amitriptyline may alter blood pressure control.

• dimenhydrinate

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

• diphenhydramine

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

• diphenoxylate hcl

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

• dipipanone

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

• disopyramide

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

• dobutamine

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

• dofetilide

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

• dolasetron

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

• donepezil

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

• dopamine

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

• dosulepin

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

• doxepin

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

• doxylamine

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

• dronedarone

  Contraindicated (2)dronedarone will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.
  
  dronedarone will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Contraindicated.Serious - Use Alternative (2)amitriptyline and dronedarone both increase QTc interval. Avoid or Use Alternate Drug.
  
  dronedarone and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• droperidol

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

• duloxetine

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

• echothiophate iodide

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

• efavirenz

  Monitor Closely (3)efavirenz will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  efavirenz and amitriptyline both increase QTc interval. Use Caution/Monitor.
  
  efavirenz will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• elagolix

  Monitor Closely (1)elagolix will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• eletriptan

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

• eliglustat

  Monitor Closely (2)eliglustat increases levels of amitriptyline 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 increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Monitor therapeutic drug concentrations, as indicated, or consider reducing the dosage of the P-gp substrate and titrate to clinical effect.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (1)elvitegravir/cobicistat/emtricitabine/tenofovir DF increases levels of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Cobicistat is a CYP2D6 inhibitor; caution with CYP2D6 substrates for which elevated plasma concentrations are associated with serious and/or life-threatening events.

• encorafenib

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

• entrectinib

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

• ephedrine

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

• eribulin

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

• erythromycin base

  Serious - Use Alternative (3)amitriptyline and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.
  
  erythromycin base will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  erythromycin base will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• erythromycin ethylsuccinate

  Serious - Use Alternative (3)amitriptyline and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.
  
  erythromycin ethylsuccinate will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  erythromycin ethylsuccinate will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• erythromycin lactobionate

  Serious - Use Alternative (3)amitriptyline and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.
  
  erythromycin lactobionate will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  erythromycin lactobionate will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• erythromycin stearate

  Serious - Use Alternative (3)amitriptyline and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.
  
  erythromycin stearate will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
  
  erythromycin stearate will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• escitalopram

  Serious - Use Alternative (2)escitalopram and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.
  
  escitalopram increases toxicity of amitriptyline by QTc interval. Avoid or Use Alternate Drug.

• esketamine intranasal

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

• eslicarbazepine acetate

  Monitor Closely (1)eslicarbazepine acetate will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.Minor (1)eslicarbazepine acetate will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• esomeprazole

  Monitor Closely (1)esomeprazole will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• estazolam

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

• estradiol

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

• estropipate

  Minor (1)estropipate, amitriptyline. 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)amitriptyline and ethanol both increase sedation. Use Caution/Monitor.Minor (1)ethanol, amitriptyline. Either increases toxicity of the other by pharmacodynamic synergism. Minor/Significance Unknown. Additive impairment of motor skills.

• ethinylestradiol

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

• etomidate

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

• etravirine

  Monitor Closely (1)etravirine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.Minor (1)etravirine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• eucalyptus

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

• ezogabine

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

• felbamate

  Monitor Closely (1)felbamate will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.

• felodipine

  Monitor Closely (1)felodipine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)felodipine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• fenfluramine

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

• fexinidazole

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

• flavoxate

  Monitor Closely (1)flavoxate and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• flecainide

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

• fluconazole

  Monitor Closely (2)fluconazole will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  fluconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline and fluconazole both increase QTc interval. Avoid or Use Alternate Drug.

• fludrocortisone

  Minor (1)fludrocortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• fluoxetine

  Monitor Closely (1)amitriptyline and fluoxetine both increase QTc interval. Modify Therapy/Monitor Closely.Serious - Use Alternative (2)fluoxetine and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.
  
  fluoxetine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Avoid or Use Alternate Drug.

• fluphenazine

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

• flurazepam

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

• fluvoxamine

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

• formoterol

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

  Monitor Closely (1)fosamprenavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)fosamprenavir increases levels of amitriptyline by decreasing metabolism. Avoid or Use Alternate Drug.

• foscarnet

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

• fosphenytoin

  Monitor Closely (2)fosphenytoin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  fosphenytoin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• fostemsavir

  Monitor Closely (1)amitriptyline 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 amitriptyline both increase serotonin levels. Modify Therapy/Monitor Closely.

• gabapentin

  Monitor Closely (1)gabapentin, amitriptyline. 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, amitriptyline. 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 amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• ganaxolone

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

• gemifloxacin

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

• gilteritinib

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

• givosiran

  Serious - Use Alternative (1)givosiran will increase the level or effect of amitriptyline 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.

• glecaprevir/pibrentasvir

  Monitor Closely (1)glecaprevir/pibrentasvir will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

• glimepiride

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

• glipizide

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

• glyburide

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

• glycopyrrolate

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

• glycopyrrolate inhaled

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

• glycopyrronium tosylate topical

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

• granisetron

  Serious - Use Alternative (2)granisetron, amitriptyline. Either increases toxicity of the other by serotonin levels. Avoid or Use Alternate Drug.
  
  granisetron and amitriptyline both increase QTc interval. Avoid or Use Alternate Drug.

• grapefruit

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

• griseofulvin

  Minor (1)griseofulvin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• guanfacine

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

• henbane

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

• homatropine

  Monitor Closely (1)homatropine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• huperzine A

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

• hydrocodone

  Monitor Closely (1)hydrocodone, amitriptyline. 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.

• hydrocortisone

  Minor (1)hydrocortisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• hydromorphone

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

• hydroxychloroquine sulfate

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

• hydroxyprogesterone caproate

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

• hyoscyamine

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

• hyoscyamine spray

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

• ibutilide

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

• iloperidone

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

• imipramine

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

• indacaterol, inhaled

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

• indinavir

  Monitor Closely (1)indinavir will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• insulin aspart

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

• insulin detemir

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

• insulin glargine

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

• insulin glulisine

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

• insulin lispro

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

• insulin NPH

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

• insulin regular human

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

• iobenguane I 123

  Contraindicated (1)amitriptyline 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)amitriptyline 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 amitriptyline 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 amitriptyline both increase serotonin levels. Contraindicated.

• isoflurane

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

• isoniazid

  Monitor Closely (2)amitriptyline and isoniazid both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  isoniazid will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.Minor (1)isoniazid will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• isoproterenol

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

• istradefylline

  Monitor Closely (1)istradefylline will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

• itraconazole

  Monitor Closely (2)itraconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  itraconazole and amitriptyline both increase QTc interval. Use Caution/Monitor.Minor (1)itraconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ivacaftor

  Monitor Closely (1)ivacaftor increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

• ivosidenib

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

• ketoconazole

  Monitor Closely (2)ketoconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  ketoconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline and ketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• ketotifen, ophthalmic

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

• L-tryptophan

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

• lapatinib

  Monitor Closely (1)amitriptyline and lapatinib both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)lapatinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lasmiditan

  Monitor Closely (2)lasmiditan, amitriptyline. 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.
  
  amitriptyline increases effects of lasmiditan by serotonin levels. Use Caution/Monitor. Coadministration may increase risk of serotonin syndrome.Serious - Use Alternative (1)lasmiditan increases effects of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• lefamulin

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

• lemborexant

  Monitor Closely (1)lemborexant, amitriptyline. 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.

• letermovir

  Monitor Closely (1)letermovir increases levels of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• levalbuterol

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

• levoketoconazole

  Monitor Closely (2)levoketoconazole will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  levoketoconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline and levoketoconazole both increase QTc interval. Avoid or Use Alternate Drug.

• levomilnacipran

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

• levorphanol

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

• linezolid

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

• lofepramine

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

• lofexidine

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

• loprazolam

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

• loratadine

  Monitor Closely (1)loratadine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• lorazepam

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

• lorcaserin

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

• lormetazepam

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

• loxapine

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

• loxapine inhaled

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

• lsd

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

• lumefantrine

  Serious - Use Alternative (1)amitriptyline and lumefantrine both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)lumefantrine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• lurasidone

  Monitor Closely (2)lurasidone, amitriptyline. Either increases toxicity of the other by sedation. Use Caution/Monitor. Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.
  
  lurasidone increases effects of amitriptyline by Other (see comment). Use Caution/Monitor. Comment: Potential for increased risk of hypotension with concurrent use. Monitor blood pressure and adjust dose of antihypertensive agent as needed.

• macimorelin

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

• maraviroc

  Monitor Closely (1)maraviroc, amitriptyline. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.

• marijuana

  Monitor Closely (1)amitriptyline and marijuana both increase sedation. Use Caution/Monitor.Minor (1)marijuana will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• mavacamten

  Monitor Closely (1)amitriptyline will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

• meclizine

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

• mefloquine

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

• meperidine

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

• meprobamate

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

• mestranol

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

• metformin

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

• methadone

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

• methamphetamine

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

• methscopolamine

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

• methylene blue

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

• methylprednisolone

  Minor (1)methylprednisolone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• metoclopramide intranasal

  Serious - Use Alternative (1)amitriptyline, 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.

• metronidazole

  Minor (1)metronidazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• metyrapone

  Minor (1)amitriptyline decreases effects of metyrapone by unspecified interaction mechanism. Minor/Significance Unknown.

• miconazole vaginal

  Minor (1)miconazole vaginal will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• midazolam

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

• midazolam intranasal

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

• miglitol

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

• milnacipran

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

• mipomersen

  Monitor Closely (1)mipomersen, amitriptyline. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Both drugs have potential to increase hepatic enzymes; monitor LFTs.

• mirabegron

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

• mirtazapine

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

• mobocertinib

  Serious - Use Alternative (1)mobocertinib will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, reduce mobocertinib dose and monitor QTc interval more frequently

• modafinil

  Monitor Closely (2)modafinil will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  amitriptyline increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

• morphine

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

• motherwort

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

• moxifloxacin

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

• moxonidine

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

• nabilone

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

• nalbuphine

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

• naratriptan

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

• nateglinide

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

• nefazodone

  Monitor Closely (2)nefazodone will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  nefazodone will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.Serious - Use Alternative (1)nefazodone and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• nefopam

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

• nelfinavir

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

• neostigmine

  Monitor Closely (1)neostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• netupitant/palonosetron

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

• nevirapine

  Minor (1)nevirapine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nicardipine

  Monitor Closely (1)nicardipine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• nifedipine

  Monitor Closely (1)nifedipine will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.Minor (1)nifedipine will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• nilotinib

  Serious - Use Alternative (1)amitriptyline and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)nilotinib will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• norepinephrine

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

• nortriptyline

  Monitor Closely (2)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.

• octreotide

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

• octreotide (Antidote)

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

• ofloxacin

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

• olanzapine

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

• oliceridine

  Monitor Closely (2)amitriptyline, oliceridine. Either increases effects of the other by serotonin levels. Modify Therapy/Monitor Closely.
  
  amitriptyline 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)amitriptyline and olodaterol inhaled both increase QTc interval. Use Caution/Monitor. TCAs prolong the QTc interval and may potentiate the effects of beta2 agonists on the cardiovascular system; increased risk of ventricular arrhythmias

• onabotulinumtoxinA

  Monitor Closely (1)onabotulinumtoxinA and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

• ondansetron

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

• opium tincture

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

• orphenadrine

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

• osilodrostat

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

• osimertinib

  Monitor Closely (1)osimertinib and amitriptyline both increase QTc interval. Use Caution/Monitor. Conduct periodic monitoring with ECGs and electrolytes in patients taking drugs known to prolong the QTc interval.

• oxaliplatin

  Monitor Closely (1)oxaliplatin will increase the level or effect of amitriptyline by Other (see comment). Use Caution/Monitor. Monitor for ECG changes if therapy is initiated in patients with drugs known to prolong QT interval.

• oxazepam

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

• oxcarbazepine

  Minor (2)oxcarbazepine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.
  
  oxcarbazepine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• oxybutynin

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

• oxybutynin topical

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

• oxybutynin transdermal

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

• oxycodone

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

• oxymetazoline intranasal

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

• ozanimod

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

• palonosetron

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

• panax ginseng

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

• pancuronium

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

• papaveretum

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

• papaverine

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

• parecoxib

  Minor (1)parecoxib will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Minor/Significance Unknown.

• paroxetine

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

• pasireotide

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

• pazopanib

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

• peginterferon alfa 2b

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

• pentazocine

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

• pentobarbital

  Monitor Closely (3)pentobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  pentobarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  pentobarbital and amitriptyline both increase sedation. Use Caution/Monitor.Minor (1)pentobarbital, amitriptyline. Other (see comment). Minor/Significance Unknown. Comment: Barbiturates may increase adverse effects, including respiratory depression, produced by toxic doses of TCAs. With therapeutic doses of TCAs, barbiturates increase metabolism and decrease blood concentrations of TCAs.

• perphenazine

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

• phendimetrazine

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

• phenobarbital

  Monitor Closely (4)phenobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  phenobarbital will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  phenobarbital and amitriptyline both increase sedation. Use Caution/Monitor.Minor (1)phenobarbital, amitriptyline. 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)amitriptyline increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, 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)amitriptyline increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, 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)amitriptyline, 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)amitriptyline increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .Serious - Use Alternative (1)amitriptyline, 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.

• phenytoin

  Monitor Closely (2)phenytoin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor therapeutic efficacy of amitriptyline; an increased dose may be required. Serum phenytoin levels should be obtained when tricyclic antidepressant agents are added to therapy due to the potential for impaired phenytoin metabolism and decreased seizure threshold. Tricyclic antidepressants when given concomitantly with anticonvulsants can increase CNS depression.
  
  phenytoin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Monitor therapeutic efficacy of amitriptyline; an increased dose may be required. Serum phenytoin levels should be obtained when tricyclic antidepressant agents are added to therapy due to the potential for impaired phenytoin metabolism and decreased seizure threshold. Tricyclic antidepressants when given concomitantly with anticonvulsants can increase CNS depression.

• pholcodine

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

• physostigmine

  Monitor Closely (1)physostigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• pilocarpine

  Monitor Closely (1)pilocarpine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• pimozide

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

• pioglitazone

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

• pirbuterol

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

• ponatinib

  Monitor Closely (1)ponatinib increases levels of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• posaconazole

  Monitor Closely (1)amitriptyline and posaconazole both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)posaconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pralidoxime

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

• prednisone

  Minor (1)prednisone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• pregabalin

  Monitor Closely (1)pregabalin, amitriptyline. 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 (3)primidone will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  primidone will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.
  
  primidone and amitriptyline both increase sedation. Use Caution/Monitor.Minor (1)primidone, amitriptyline. 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)amitriptyline and procainamide both increase QTc interval. Contraindicated.

• procarbazine

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

• prochlorperazine

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

• progesterone micronized

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

• promethazine

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

• propantheline

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

• propofol

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

• propylhexedrine

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

• pseudoephedrine

  Serious - Use Alternative (1)amitriptyline 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 amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• quazepam

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

• quercetin

  Monitor Closely (1)quercetin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• quetiapine

  Monitor Closely (2)quetiapine and amitriptyline both increase sedation. Use Caution/Monitor.
  
  quetiapine, amitriptyline. Either increases toxicity of the other by QTc interval. Use Caution/Monitor. Avoid use with drugs that prolong QT and in patients with risk factors for prolonged QT interval. Postmarketing cases show QT prolongation with overdose in patients with concomitant illness or with drugs known to cause electrolyte imbalance or prolong QT.

• quinidine

  Contraindicated (1)quinidine and amitriptyline both increase QTc interval. Contraindicated.Serious - Use Alternative (1)quinidine will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

• quinine

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

• quinupristin/dalfopristin

  Minor (1)quinupristin/dalfopristin will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ramelteon

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

• ranolazine

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

• rapacuronium

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

• rasagiline

  Serious - Use Alternative (1)rasagiline and amitriptyline 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.

• remifentanil

  Monitor Closely (1)amitriptyline, remifentanil. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. May also increase risk of serotonin syndrome.

• remimazolam

  Monitor Closely (1)remimazolam, amitriptyline. 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)amitriptyline increases effects of repaglinide by pharmacodynamic synergism. Minor/Significance Unknown.

• ribociclib

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

• rifabutin

  Monitor Closely (2)rifabutin decreases levels of amitriptyline by increasing metabolism. Use Caution/Monitor.
  
  rifabutin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rifampin

  Monitor Closely (3)rifampin will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  rifampin will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  rifampin will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rifapentine

  Monitor Closely (1)rifapentine will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

• rilpivirine

  Monitor Closely (1)rilpivirine increases toxicity of amitriptyline by QTc interval. Use Caution/Monitor. Rilpivirine should be used with caution when co-administered with a drug with a known risk of Torsades de Pointes.

• risperidone

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

• ritonavir

  Monitor Closely (2)ritonavir will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
  
  ritonavir will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• rivastigmine

  Monitor Closely (1)rivastigmine increases and amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• rizatriptan

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

• rocuronium

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

• rolapitant

  Monitor Closely (1)rolapitant will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor. Rolapitant may increase plasma concentrations of CYP2D6 substrates for at least 28 days following rolapitant administration.

• romidepsin

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

• rosiglitazone

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

• rufinamide

  Minor (1)rufinamide will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• safinamide

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

• sage

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

• salmeterol

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

• sarecycline

  Monitor Closely (1)sarecycline will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

• saxagliptin

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

• scopolamine

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

• scullcap

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

• secobarbital

  Monitor Closely (2)secobarbital will decrease the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  secobarbital and amitriptyline both increase sedation. Use Caution/Monitor.Minor (1)secobarbital, amitriptyline. 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 amitriptyline 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 amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• selinexor

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

• serdexmethylphenidate/dexmethylphenidate

  Serious - Use Alternative (1)amitriptyline, 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 amitriptyline by decreasing metabolism. Minor/Significance Unknown.

• sertraline

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

• sevoflurane

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

• shepherd's purse

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

• simvastatin

  Monitor Closely (1)simvastatin will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• sirolimus

  Monitor Closely (1)sirolimus will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• sitagliptin

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

• sodium oxybate

  Serious - Use Alternative (1)amitriptyline, 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 amitriptyline 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 amitriptyline 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)amitriptyline, sodium sulfate/potassium sulfate/magnesium sulfate/polyethylene glycol. Other (see comment). Use Caution/Monitor. Comment: Caution when bowel preps are used with drugs that cause SIADH or NSAIDs; increased risk for water retention or electrolyte imbalance.

• solifenacin

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

• sorafenib

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

• sotalol

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

• St John's Wort

  Monitor Closely (2)St John's Wort will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  St John's Wort will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.Serious - Use Alternative (1)amitriptyline and St John's Wort both increase serotonin levels. Avoid or Use Alternate Drug.

• stiripentol

  Monitor Closely (1)stiripentol, amitriptyline. 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 amitriptyline decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.

• sufentanil

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

• sufentanil SL

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

• sumatriptan

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

• sumatriptan intranasal

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

• suvorexant

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

• tacrolimus

  Monitor Closely (1)tacrolimus will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• tapentadol

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

• tedizolid

  Serious - Use Alternative (1)tedizolid, amitriptyline. 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)amitriptyline and telavancin both increase QTc interval. Modify Therapy/Monitor Closely.

• temazepam

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

• terbinafine

  Monitor Closely (1)terbinafine will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2D6 metabolism. Modify Therapy/Monitor Closely. Assess need to reduce dose of CYP2D6-metabolized drug.

• terbutaline

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

• teriflunomide

  Monitor Closely (1)teriflunomide decreases levels of amitriptyline by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• thioridazine

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

• thiothixene

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

• tiotropium

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

• tolazamide

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

• tolbutamide

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

• tolterodine

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

• tolvaptan

  Monitor Closely (1)tolvaptan will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

• topiramate

  Monitor Closely (2)topiramate increases toxicity of amitriptyline by unspecified interaction mechanism. Use Caution/Monitor. Amitriptyline levels may increase; adjust dose based on clinical response and not on basis of plasma levels.
  
  amitriptyline and topiramate both increase sedation. Modify Therapy/Monitor Closely.

• toremifene

  Serious - Use Alternative (1)amitriptyline 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)amitriptyline and tramadol both increase serotonin levels. Modify Therapy/Monitor Closely.
  
  tramadol and amitriptyline both increase sedation. Use Caution/Monitor.

• tranylcypromine

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

• trazodone

  Monitor Closely (3)trazodone will decrease the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
  
  amitriptyline and trazodone both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  amitriptyline and trazodone both increase sedation. Use Caution/Monitor.Serious - Use Alternative (2)amitriptyline and trazodone both increase QTc interval. Avoid or Use Alternate Drug.
  
  trazodone and amitriptyline both increase serotonin levels. Avoid or Use Alternate Drug.

• triazolam

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

• triclofos

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

• trifluoperazine

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

• trihexyphenidyl

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

• trimethoprim

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

• trimipramine

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

• triprolidine

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

• tropisetron

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

• trospium chloride

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

• tucatinib

  Monitor Closely (1)tucatinib will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

• umeclidinium bromide/vilanterol inhaled

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

• valerian

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

• vandetanib

  Serious - Use Alternative (1)amitriptyline, 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)amitriptyline increases effects of vasopressin by pharmacodynamic synergism. Minor/Significance Unknown.

• vecuronium

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

• vemurafenib

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

• verapamil

  Monitor Closely (1)verapamil will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. The frequency and severity of amitriptyline adverse effects (sedation, anticholinergic effects and orthostatic hypotension) may be increased. Cardiac dysrhythmic effects may be additive. Minor (2)verapamil will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
  
  verapamil increases levels of amitriptyline by decreasing metabolism. Minor/Significance Unknown.

• vilanterol/fluticasone furoate inhaled

  Serious - Use Alternative (2)amitriptyline 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
  
  amitriptyline 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)amitriptyline, 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)amitriptyline increases effects of vildagliptin by pharmacodynamic synergism. Minor/Significance Unknown.

• voclosporin

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

• voriconazole

  Monitor Closely (2)voriconazole will increase the level or effect of amitriptyline by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor.
  
  amitriptyline and voriconazole both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)voriconazole will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• vortioxetine

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

• warfarin

  Monitor Closely (1)amitriptyline increases effects of warfarin by unspecified interaction mechanism. Use Caution/Monitor.

• xylometazoline

  Monitor Closely (1)amitriptyline increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)amitriptyline, 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, amitriptyline. Mechanism: unspecified interaction mechanism. Contraindicated. May cause increase or decrease in blood pressure.

• yohimbine

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

• zafirlukast

  Minor (1)zafirlukast will increase the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

• ziconotide

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

• ziprasidone

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

• zolmitriptan

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

• zolpidem

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