amitriptyline (Rx)

Brand and Other Names:Elavil, Levate
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

tablet

  • 10mg
  • 25mg
  • 50mg
  • 75mg
  • 100mg
  • 150mg

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

Dosage Forms & Strengths

tablet

  • 10mg
  • 25mg
  • 50mg
  • 75mg
  • 100mg
  • 150mg

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

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Interactions

Interaction Checker

and amitriptyline

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            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 (131)

            • 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/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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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 (373)

            • 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.

            • alfentanil

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

            • alfuzosin

              amitriptyline and alfuzosin 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.

            • 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. Modify Therapy/Monitor Closely.

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

            • 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.

            • 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.

            • aripiprazole

              aripiprazole and amitriptyline both increase sedation. 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • desflurane

              desflurane and amitriptyline both increase sedation. 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • 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.

            • pilocarpine ophthalmic

              pilocarpine ophthalmic 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.

            • 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.

            • 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.

            • 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 (105)

            • acarbose

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

            • amobarbital

              amobarbital, 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.

            • 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.

            • modafinil

              modafinil will decrease the level or effect of amitriptyline by affecting hepatic/intestinal enzyme CYP3A4 metabolism. 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.

            • 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.

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            Adverse Effects

            Frequency Not Defined

            Agitation

            Agranulocytosis

            Alopecia

            Anxiety

            Anorexia

            Ataxia

            Arrhythmia

            Blurred vision

            Coma

            Confusion

            Constipation

            Diarrhea

            Dizziness

            Dry mouth

            ECG changes

            Eosinophilia

            Extrapyramidal symptoms (EPS)

            Fatigue

            Hallucination

            Headache

            Hypertension

            Increased LFTs

            Insomnia

            Lethargy

            Leukopenia

            MI

            Nausea

            Ocular pressure increased

            Orthostatic hypotension

            Palpitation

            Paresthesia

            Photosensitivity

            Rash

            Restlessness

            Sedation

            Seizure

            Sexual dysfunction

            SIADH

            Stroke

            Stomatitis

            Syncope

            Sweating

            Tachycardia

            Thrombocytopenia

            Tinnitus

            Urinary retention

            Urticaria

            Vomiting

            Xerostomia

            Weakness

            Weight gain

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            Warnings

            Black Box Warnings

            In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 years) taking antidepressants for major depressive disorders and other psychiatric illnesses; this increase was not seen in patients over age 24 years; a slight decrease in suicidal thinking was seen in adults over age 65 years

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

            Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during the initial 1-2 months of therapy and dosage adjustments; the patient’s family should communicate any abrupt changes in behavior to the healthcare provider

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

            This drug is not approved for use in pediatric patients <12 years

            Not FDA approved for treatment of bipolar depression

            Contraindications

            Hypersensitivity

            Acute recovery phase following MI

            Concurrent use with cisapride

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

            Cautions

            Bone marrow suppression reported

            Avoid use in narrow-angle glaucoma

            May cause sedation and impair mental and physical abilities

            Avoid use with any drugs or conditions that prolong QT interval

            May cause orthostatic hypotension

            Use caution in patients with cardiovascular disease, diabetes, mania, hepatic and renal impairment, thyroid dysfunction, and seizure disorder

            May worsen mania symptoms or precipitate mania in patients with bipolar disorder

            Clinical worsening and suicidal ideation may occur despite medication in adolescents and young adults (18-24 years)

            Risk of anticholinergic side effects; may cause constipation, urinary retention, blurred vision, and xerostomia

            Use caution in patients with urinary retention, open-angle glaucoma, BPH, decreased gastrointestinal motility, or paralytic ileus

            Possibility of EPS and neuroleptic malignant syndrome

            Abrupt discontinuation of therapy not recommended in patients receiving high doses for prolonged periods

            Fractures reported with therapy

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            Pregnancy & Lactation

            Pregnancy category: C

            Lactation: Distributed in breast milk; do not nurse (AAP states effect on nursing infants is unknown but may be of concern)

            Pregnancy Categories

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

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

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

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

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

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Neurotransmitter (especially norepinephrine and serotonin) reuptake inhibitor; anticholinergic

            Absorption

            Peak serum time: 4 hr

            Metabolism

            Metabolized by hepatic CYP2C19, CYP3A4

            Metabolites: Nortriptyline

            Elimination

            Half-life: 9-27 hr

            Excretion: Urine (18%), small amounts in feces

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
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            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            Patient Education
            amitriptyline oral

            AMITRIPTYLINE - ORAL

            (A-mi-TRIP-ti-leen)

            COMMON BRAND NAME(S): Elavil

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

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

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

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

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

            DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Some products that may interact with this drug include: arbutamine, disulfiram, thyroid supplements, other drugs that can cause bleeding/bruising (including antiplatelet drugs such as clopidogrel, NSAIDs such as ibuprofen, "blood thinners" such as warfarin), anticholinergic drugs (such as belladonna alkaloids), certain drugs for high blood pressure (drugs that work in the brain such as clonidine, guanabenz).Taking MAO inhibitors with this medication may cause a serious (possibly fatal) drug interaction. Avoid taking MAO inhibitors (isocarboxazid, linezolid, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, safinamide, selegiline, tranylcypromine) during treatment with this medication. Most MAO inhibitors should also not be taken for two weeks before and after treatment with this medication. Ask your doctor when to start or stop taking this medication.Other medications can affect the removal of amitriptyline from your body, thereby affecting how amitriptyline works. These drugs include cimetidine, terbinafine, drugs to treat irregular heart rate (such as quinidine/propafenone/flecainide), antidepressants (such as SSRIs including paroxetine/fluoxetine/fluvoxamine). This is not a complete list.Many drugs besides amitriptyline may affect the heart rhythm (QT prolongation in the EKG), including amiodarone, cisapride, dofetilide, pimozide, procainamide, quinidine, sotalol, macrolide antibiotics (such as erythromycin), among others. Therefore, before using amitriptyline, report all medications you are currently using to your doctor or pharmacist.Tell your doctor or pharmacist if you are taking other products that cause drowsiness, including alcohol, marijuana (cannabis), antihistamines (such as cetirizine, diphenhydramine), drugs for sleep or anxiety (such as alprazolam, diazepam, zolpidem), muscle relaxants, and opioid pain relievers (such as codeine).Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain decongestants or ingredients that cause drowsiness. Ask your pharmacist about using those products safely.Aspirin can increase the risk of bleeding when used with this medication. However, if your doctor has directed you to take low-dose aspirin for heart attack or stroke prevention (usually 81-162 milligrams a day), you should continue taking it unless your doctor instructs you otherwise. Ask your doctor or pharmacist for more details.Amitriptyline is very similar to nortriptyline. Do not use medications containing nortriptyline while using amitriptyline.

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

            NOTES: Do not share this medication with others.Laboratory and/or medical tests (such as EKG, liver tests, amitriptyline blood level) may be performed from time to time to monitor your progress or check for side effects. Keep all medical appointments. Consult your doctor for more details.

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

            STORAGE: Store at room temperature between 68-77 degrees F (20-25 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

            Information last revised March 2021. Copyright(c) 2021 First Databank, Inc.

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

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            Formulary

            FormularyPatient Discounts

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

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

            Adding plans allows you to:

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

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

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