doxepin (Rx)

Brand and Other Names:Silenor
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

capsule (generic)

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

tablet (Silenor)

  • 3mg
  • 6mg

oral concentrate (generic)

  • 10mg/mL

Depression/Anxiety

Initiate at low dose (25 mg/day); gradually titrate upward every 5-7 days

Dosage range: 25-300 mg/day PO, up to 150 mg/day as single dose

If dose exceeds 150 mg/day, divide q12hr

Dosing considerations

  • May give qHS to decrease daytime sedation

Insomnia (Silenor)

Sleep maintenance

3-6 mg PO within 30 minutes before bedtime; not to exceed 6 mg/day

Hepatic impairment/debilitated patients: 3 mg PO within 30 minutes before bedtime

Dosing considerations

  • To minimize potential for next day drowsiness, do not take within 3 hr of a meal (AUC increased by 41% and Cmax by 15% when taken with high fat meal)

Dosing Modifications

Hepatic impairment: Use lower dose and adjust gradually for depression; initiate Silenor at 3 mg daily for insomnia

<12 years old: Not recommended

Insomnia (Silenor)

Sleep maintenance

Starting dose: 3 mg PO within 30 minutes before bedtime

May increase to 6 mg PO HS if clinically indicated

Depression/Anxiety

Lower initial dose (ie, 10 mg/day) and adjust gradually; 10-25 mg PO qHS

May increase by 10-25 mg increments q3Day for inpatients and weekly for outpatients if tolerated

Dosing considerations

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

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

May cause confusion and oversedation in elderly

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Interactions

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            Contraindicated (17)

            • disopyramide

              doxepin and disopyramide both increase QTc interval. Contraindicated.

            • ibutilide

              doxepin and ibutilide both increase QTc interval. Contraindicated.

            • indapamide

              doxepin and indapamide both increase QTc interval. Contraindicated.

            • iobenguane I 123

              doxepin 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 doxepin both increase serotonin levels. Contraindicated.

            • lefamulin

              lefamulin will increase the level or effect of doxepin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Lefamulin is contraindicated with CYP3A substrates know to prolong the QT interval.

            • pentamidine

              doxepin and pentamidine both increase QTc interval. Contraindicated.

            • phenelzine

              phenelzine and doxepin both increase serotonin levels. Contraindicated.

            • pimozide

              doxepin and pimozide both increase QTc interval. Contraindicated.

            • procainamide

              doxepin and procainamide both increase QTc interval. Contraindicated.

            • procarbazine

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

            • quinidine

              quinidine and doxepin both increase QTc interval. Contraindicated.

            • safinamide

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

            • selegiline

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

            • sotalol

              doxepin and sotalol both increase QTc interval. Contraindicated.

            • thioridazine

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

            • tranylcypromine

              tranylcypromine and doxepin both increase serotonin levels. Contraindicated.

            Serious - Use Alternative (144)

            • abametapir

              abametapir will increase the level or effect of doxepin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • albuterol

              doxepin, 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

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

            • amitriptyline

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

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

            • amoxapine

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

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

            • arformoterol

              doxepin, 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

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

            • artemether

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

            • artemether/lumefantrine

              artemether/lumefantrine will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug.

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

            • benzphetamine

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

            • buprenorphine

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

            • buspirone

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

            • calcium/magnesium/potassium/sodium oxybates

              doxepin, 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.

            • chloroquine

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

            • chlorpromazine

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

            • citalopram

              citalopram and doxepin 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.

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

            • clarithromycin

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

            • clomipramine

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

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

            • clonidine

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

            • cyclobenzaprine

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

            • dacomitinib

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

            • desipramine

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

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

            • desvenlafaxine

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

            • dexfenfluramine

              doxepin, 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

              doxepin, 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

              doxepin, 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

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

            • diethylpropion

              doxepin, 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

              doxepin, 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

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

            • dolasetron

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

            • dopamine

              doxepin, 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

              doxepin, 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.

            • dronedarone

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

            • droperidol

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

            • duloxetine

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

            • encorafenib

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

            • ephedrine

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

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

              doxepin, 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

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

            • erythromycin ethylsuccinate

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

            • erythromycin lactobionate

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

            • erythromycin stearate

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

            • escitalopram

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

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

            • fenfluramine

              doxepin, 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 doxepin both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.

              fexinidazole will increase the level or effect of doxepin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • fluconazole

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

            • fluoxetine

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

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

            • fluphenazine

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

            • fluvoxamine

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

            • formoterol

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

              doxepin, 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 doxepin by decreasing metabolism. Avoid or Use Alternate Drug.

            • givosiran

              givosiran will increase the level or effect of doxepin 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.

            • glasdegib

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

            • granisetron

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

            • guanfacine

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

            • haloperidol

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

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

            • hydroxychloroquine sulfate

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

            • imipramine

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

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

            • inotuzumab

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

            • iobenguane I 131

              doxepin 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

              doxepin, 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

              doxepin and ivosidenib both decrease QTc interval. Avoid or Use Alternate Drug.

            • ketoconazole

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

            • lenvatinib

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

            • levalbuterol

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

            • levoketoconazole

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

            • levomilnacipran

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

            • linezolid

              linezolid and doxepin 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

              doxepin, 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

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

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

            • lopinavir

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

            • lorcaserin

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

            • lumefantrine

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

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

            • macimorelin

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

            • maprotiline

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

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

            • mefloquine

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

            • meperidine

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

            • metaproterenol

              doxepin, 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

              doxepin, 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 doxepin 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

              doxepin, 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

              doxepin, 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

              doxepin, 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.

            • midostaurin

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

            • milnacipran

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

            • mirtazapine

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

            • moxifloxacin

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

            • nefazodone

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

            • netupitant/palonosetron

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

            • nilotinib

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

            • norepinephrine

              doxepin, 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

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

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

            • octreotide

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

            • octreotide (Antidote)

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

            • ondansetron

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

            • osimertinib

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

            • ozanimod

              ozanimod increases toxicity of doxepin 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.

              doxepin and ozanimod both increase QTc interval. Contraindicated.

            • palonosetron

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

            • panobinostat

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

            • paroxetine

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

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

            • perphenazine

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

            • phendimetrazine

              doxepin, 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

              doxepin, 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

              doxepin, 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

              doxepin, 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

              doxepin, 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

              doxepin 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.

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

            • ponesimod

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

            • primaquine

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

            • promazine

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

            • propylhexedrine

              doxepin, 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

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

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

            • pseudoephedrine

              doxepin 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 doxepin by affecting hepatic enzyme CYP2D6 metabolism. Avoid or Use Alternate Drug. Both agents increase QTc interval.

            • quinine

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

            • rasagiline

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

            • ribociclib

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

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

            • salmeterol

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

            • selinexor

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

            • serdexmethylphenidate/dexmethylphenidate

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

            • sertraline

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

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

            • sodium oxybate

              doxepin, 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

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

            • tedizolid

              tedizolid, doxepin. 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

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

            • toremifene

              doxepin 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

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

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

            • trifluoperazine

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

            • trimipramine

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

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

            • tucatinib

              tucatinib will increase the level or effect of doxepin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • umeclidinium bromide/vilanterol inhaled

              doxepin 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

              doxepin, 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.

            • venlafaxine

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

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

            • vilanterol/fluticasone furoate inhaled

              doxepin 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

            • vilazodone

              doxepin, 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

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

            • xylometazoline

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

            • yohimbine

              doxepin, 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

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

            Monitor Closely (369)

            • 5-HTP

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

            • abiraterone

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

            • albuterol

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

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

            • alfentanil

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

            • alfuzosin

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

            • almotriptan

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

            • alprazolam

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

            • amifampridine

              doxepin 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 doxepin by affecting hepatic enzyme CYP2D6 metabolism. Use Caution/Monitor.

            • amisulpride

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

            • amitriptyline

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

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

            • amobarbital

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

            • amoxapine

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

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

            • anagrelide

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

            • anticholinergic/sedative combos

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

            • apomorphine

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

              doxepin and apomorphine both increase QTc interval. Use Caution/Monitor.

            • arformoterol

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

              doxepin and arformoterol both increase QTc interval. Use Caution/Monitor.

            • aripiprazole

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

              doxepin and aripiprazole both increase QTc interval. Use Caution/Monitor.

            • armodafinil

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

            • asenapine

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

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

            • atazanavir

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

            • atomoxetine

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

            • atracurium

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

            • atropine

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

            • atropine IV/IM

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

            • azelastine

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

            • azithromycin

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

            • baclofen

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

            • bedaquiline

              doxepin and bedaquiline both increase QTc interval. Use Caution/Monitor.

            • belladonna alkaloids

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

            • belladonna and opium

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

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

            • benperidol

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

            • benzhydrocodone/acetaminophen

              benzhydrocodone/acetaminophen, doxepin. 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

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

            • benztropine

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

            • bethanechol

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

            • brompheniramine

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

            • buprenorphine

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

            • buprenorphine buccal

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

            • buprenorphine subdermal implant

              doxepin, 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

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

            • bupropion

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

              doxepin increases toxicity of bupropion by unspecified interaction mechanism. Use Caution/Monitor. May lower seizure threshold; keep bupropion dose as low as possible.

            • butabarbital

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

            • butalbital

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

            • butorphanol

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

            • caffeine

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

            • carbachol

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

            • carbinoxamine

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

            • carisoprodol

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

            • celecoxib

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

            • cenobamate

              cenobamate will decrease the level or effect of doxepin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

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

            • ceritinib

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

            • cevimeline

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

            • chloral hydrate

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

            • chlordiazepoxide

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

            • chloroquine

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

            • chlorpheniramine

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

            • chlorpromazine

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

            • chlorzoxazone

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

            • cimetidine

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

            • cinnarizine

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

            • ciprofloxacin

              doxepin and ciprofloxacin both increase QTc interval. Use Caution/Monitor.

            • cisatracurium

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

            • clemastine

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

            • clobazam

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

              doxepin, clobazam. Other (see comment). Use Caution/Monitor. Comment: Concomitant administration can increase the potential for CNS effects (e.g., increased sedation or respiratory depression).

            • clofazimine

              doxepin and clofazimine both increase QTc interval. Use Caution/Monitor.

            • clomipramine

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

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

            • clonazepam

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

            • clorazepate

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

            • clozapine

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

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

            • cobicistat

              cobicistat will increase the level or effect of doxepin 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 doxepin 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

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

            • codeine

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

            • crizotinib

              doxepin and crizotinib both increase QTc interval. Use Caution/Monitor.

            • cyclizine

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

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

            • cyclobenzaprine

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

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

            • cyproheptadine

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

            • dabrafenib

              dabrafenib will decrease the level or effect of doxepin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

            • dantrolene

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

            • daridorexant

              doxepin and daridorexant both increase sedation. Modify Therapy/Monitor Closely. Coadministration increases risk of CNS depression, which can lead to additive impairment of psychomotor performance and cause daytime impairment.

            • darifenacin

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

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

            • dasatinib

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

            • debrisoquine

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

            • degarelix

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

            • desflurane

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

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

            • desipramine

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

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

            • desvenlafaxine

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

            • deutetrabenazine

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

              deutetrabenazine and doxepin both increase QTc interval. Use Caution/Monitor.

            • dexchlorpheniramine

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

            • dexfenfluramine

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

              doxepin and dexfenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.

            • dexmedetomidine

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

            • dexmethylphenidate

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

            • dextroamphetamine

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

              doxepin and dextroamphetamine both increase serotonin levels. Modify Therapy/Monitor Closely.

              doxepin increases effects of dextroamphetamine by unknown mechanism. Use Caution/Monitor.

            • dextroamphetamine transdermal

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

            • dextromoramide

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

            • diamorphine

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

            • diazepam

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

            • diazepam intranasal

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

            • dichlorphenamide

              dichlorphenamide and doxepin both decrease serum potassium. Use Caution/Monitor.

            • dicyclomine

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

            • diethylpropion

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

            • difelikefalin

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

            • difenoxin hcl

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

            • dihydroergotamine

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

            • dihydroergotamine intranasal

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

            • dimenhydrinate

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

            • diphenhydramine

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

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

            • diphenoxylate hcl

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

            • dipipanone

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

            • dobutamine

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

            • dolasetron

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

            • donepezil

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

              donepezil and doxepin both increase QTc interval. Use Caution/Monitor.

            • dopamine

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

            • dopexamine

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

            • doxylamine

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

            • droperidol

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

            • echothiophate iodide

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

            • efavirenz

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

            • eletriptan

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

            • eliglustat

              eliglustat increases levels of doxepin 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.

              doxepin and eliglustat both increase QTc interval. Use Caution/Monitor.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

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

            • entrectinib

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

            • ephedrine

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

              doxepin increases effects of ephedrine by unknown mechanism. Use Caution/Monitor.

            • epinephrine

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

              doxepin increases effects of epinephrine by unknown mechanism. Use Caution/Monitor.

            • epinephrine inhaled

              doxepin 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

              doxepin increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

              doxepin increases effects of epinephrine racemic by unknown mechanism. Use Caution/Monitor.

            • ergotamine

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

            • eribulin

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

            • esketamine intranasal

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

            • estazolam

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

            • ethanol

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

            • etomidate

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

            • fedratinib

              fedratinib will increase the level or effect of doxepin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

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

            • fenfluramine

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

              doxepin and fenfluramine both increase serotonin levels. Modify Therapy/Monitor Closely.

              fenfluramine, doxepin. 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 doxepin both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • fingolimod

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

            • flavoxate

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

            • flecainide

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

            • fluoxetine

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

            • fluphenazine

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

            • flurazepam

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

            • formoterol

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

            • foscarnet

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

            • fostemsavir

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

            • frovatriptan

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

            • gabapentin

              gabapentin, doxepin. 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, doxepin. 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.

            • gadobenate

              gadobenate and doxepin both increase QTc interval. Use Caution/Monitor.

            • galantamine

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

            • ganaxolone

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

            • gemifloxacin

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

            • gemtuzumab

              doxepin and gemtuzumab both increase QTc interval. Use Caution/Monitor.

            • gilteritinib

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

            • glycopyrrolate

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

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

            • glycopyrrolate inhaled

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

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

            • glycopyrronium tosylate topical

              glycopyrronium tosylate topical, doxepin. 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.

            • goserelin

              doxepin and goserelin both increase QTc interval. Use Caution/Monitor.

            • granisetron

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

            • haloperidol

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

            • henbane

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

            • histrelin

              doxepin and histrelin both increase QTc interval. Use Caution/Monitor.

            • homatropine

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

            • huperzine A

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

            • hydrocodone

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

            • hydroxyzine

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

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

            • hyoscyamine

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

            • hyoscyamine spray

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

            • iloperidone

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

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

              iloperidone increases levels of doxepin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Iloperidone is a time-dependent CYP3A inhibitor and may lead to increased plasma levels of drugs predominantly eliminated by CYP3A4.

            • imatinib

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

            • imipramine

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

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

            • indacaterol, inhaled

              indacaterol, inhaled, doxepin. QTc interval. Use Caution/Monitor. Drugs that are known to prolong the QTc interval may have an increased the risk of ventricular arrhythmias.

            • ipratropium

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

            • isoflurane

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

            • isoniazid

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

            • isoproterenol

              doxepin 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 doxepin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

            • itraconazole

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

            • ketamine

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

            • ketotifen, ophthalmic

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

            • L-tryptophan

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

            • lapatinib

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

            • lasmiditan

              lasmiditan, doxepin. 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.

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

            • lefamulin

              doxepin and lefamulin both increase QTc interval. Use Caution/Monitor.

            • lemborexant

              lemborexant, doxepin. 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.

            • leuprolide

              doxepin and leuprolide both increase QTc interval. Use Caution/Monitor.

            • levalbuterol

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

              doxepin and levalbuterol both increase QTc interval. Use Caution/Monitor.

            • levofloxacin

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

            • levorphanol

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

            • lisdexamfetamine

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

              doxepin, 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

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

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

            • lofepramine

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

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

            • lofexidine

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

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

              doxepin and lofexidine both increase QTc interval. Use Caution/Monitor.

            • loperamide

              doxepin and loperamide both increase QTc interval. Use Caution/Monitor.

            • loprazolam

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

            • lorazepam

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

            • lorcaserin

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

            • lormetazepam

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

            • loxapine

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

            • loxapine inhaled

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

            • lsd

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

            • lurasidone

              lurasidone increases effects of doxepin 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.

            • maprotiline

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

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

            • marijuana

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

            • meclizine

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

            • melatonin

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

            • meperidine

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

            • meprobamate

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

            • metaproterenol

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

            • metaxalone

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

            • methadone

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

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

            • methamphetamine

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

            • methocarbamol

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

            • methscopolamine

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

            • methylenedioxymethamphetamine

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

            • methylphenidate

              doxepin, 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 doxepin both increase sedation. Use Caution/Monitor.

            • midazolam intranasal

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

            • midodrine

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

            • mifepristone

              doxepin and mifepristone both increase QTc interval. Use Caution/Monitor.

            • mirabegron

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

            • mirtazapine

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

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

            • mitotane

              mitotane decreases levels of doxepin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Mitotane is a strong inducer of cytochrome P-4503A4; monitor when coadministered with CYP3A4 substrates for possible dosage adjustments.

            • mobocertinib

              doxepin and mobocertinib both increase QTc interval. Use Caution/Monitor.

            • modafinil

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

            • morphine

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

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

            • motherwort

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

            • moxonidine

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

            • nabilone

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

            • nalbuphine

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

            • naratriptan

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

            • nefopam

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

            • neostigmine

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

            • nilotinib

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

            • norepinephrine

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

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

            • nortriptyline

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

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

            • ofloxacin

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

            • olanzapine

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

              doxepin and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances

            • oliceridine

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

              doxepin 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

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

            • onabotulinumtoxinA

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

            • ondansetron

              doxepin and ondansetron both increase QTc interval. Use Caution/Monitor.

            • opium tincture

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

            • orphenadrine

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

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

            • osilodrostat

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

            • oxaliplatin

              doxepin and oxaliplatin both increase QTc interval. Use Caution/Monitor.

            • oxazepam

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

            • oxybutynin

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

            • oxybutynin topical

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

            • oxybutynin transdermal

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

            • oxycodone

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

            • oxymetazoline intranasal

              doxepin 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 doxepin both increase sedation. Use Caution/Monitor.

            • paliperidone

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

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

            • pancuronium

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

            • papaveretum

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

            • papaverine

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

            • paroxetine

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

            • pasireotide

              doxepin and pasireotide both increase QTc interval. Use Caution/Monitor.

            • pazopanib

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

            • peginterferon alfa 2b

              peginterferon alfa 2b, doxepin. 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 doxepin both increase sedation. Use Caution/Monitor.

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

            • pentobarbital

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

            • perphenazine

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

            • phendimetrazine

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

            • phenobarbital

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

            • phentermine

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

            • phenylephrine

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

            • phenylephrine ophthalmic

              doxepin, 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

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

            • pholcodine

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

            • physostigmine

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

            • pilocarpine

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

            • pimavanserin

              doxepin and pimavanserin both increase QTc interval. Use Caution/Monitor.

            • pimozide

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

            • pirbuterol

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

            • posaconazole

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

            • pralidoxime

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

            • pregabalin

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

            • primidone

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

            • prochlorperazine

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

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

            • promethazine

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

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

            • propafenone

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

              doxepin and propafenone both increase QTc interval. Use Caution/Monitor.

            • propantheline

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

            • propofol

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

            • propylhexedrine

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

            • protriptyline

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

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

            • pyridostigmine

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

            • quazepam

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

            • quetiapine

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

              doxepin and quetiapine both increase QTc interval. Use Caution/Monitor.

            • ramelteon

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

              doxepin will increase the level or effect of ramelteon by unspecified interaction mechanism. Use Caution/Monitor. AUC and Cmax increased by 66% and 69% respectively.

            • ranolazine

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

            • rapacuronium

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

            • remifentanil

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

            • remimazolam

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

            • rifabutin

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

            • rilpivirine

              doxepin and rilpivirine both increase QTc interval. Use Caution/Monitor.

            • risperidone

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

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

            • ritonavir

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

            • rivastigmine

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

            • rizatriptan

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

            • rocuronium

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

            • rolapitant

              rolapitant will increase the level or effect of doxepin 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

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

            • salmeterol

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

              doxepin and salmeterol both increase QTc interval. Use Caution/Monitor.

            • SAMe

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

            • saquinavir

              doxepin and saquinavir both increase QTc interval. Use Caution/Monitor.

            • scopolamine

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

            • scullcap

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

            • secobarbital

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

            • selpercatinib

              doxepin and selpercatinib both increase QTc interval. Use Caution/Monitor.

            • sevoflurane

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

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

            • shepherd's purse

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

            • siponimod

              doxepin and siponimod both increase QTc interval. Use Caution/Monitor.

            • sodium sulfate/?magnesium sulfate/potassium chloride

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

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

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

            • sorafenib

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

            • stiripentol

              stiripentol, doxepin. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

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

            • sufentanil

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

            • sufentanil SL

              sufentanil SL, doxepin. 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

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

            • sumatriptan

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

            • sumatriptan intranasal

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

            • sunitinib

              doxepin and sunitinib both increase QTc interval. Use Caution/Monitor.

            • suvorexant

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

            • tacrolimus

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

            • tapentadol

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

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

            • telavancin

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

            • temazepam

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

            • terbinafine

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

            • terbutaline

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

            • teriflunomide

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

            • thioridazine

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

            • thiothixene

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

              doxepin and thiothixene both increase QTc interval. Use Caution/Monitor.

            • tiotropium

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

            • tolterodine

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

            • topiramate

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

            • tramadol

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

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

            • trazodone

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

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

            • triazolam

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

            • triclabendazole

              doxepin and triclabendazole both increase QTc interval. Use Caution/Monitor.

            • triclofos

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

            • trifluoperazine

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

            • trihexyphenidyl

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

            • trimethoprim

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

            • trimipramine

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

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

            • triprolidine

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

            • triptorelin

              doxepin and triptorelin both increase QTc interval. Use Caution/Monitor.

            • tropisetron

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

            • trospium chloride

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

            • umeclidinium bromide/vilanterol inhaled

              doxepin and umeclidinium bromide/vilanterol inhaled both decrease QTc interval. Use Caution/Monitor.

            • valerian

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

            • vardenafil

              doxepin and vardenafil both increase QTc interval. Use Caution/Monitor.

            • vecuronium

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

            • vemurafenib

              doxepin and vemurafenib both increase QTc interval. Use Caution/Monitor.

            • venlafaxine

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

            • voclosporin

              doxepin and voclosporin both increase QTc interval. Use Caution/Monitor.

            • voriconazole

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

            • vorinostat

              doxepin and vorinostat both increase QTc interval. Use Caution/Monitor.

            • xylometazoline

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

            • yohimbine

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

            • ziconotide

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

            • ziprasidone

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

            • zolmitriptan

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

            Minor (81)

            • acarbose

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

            • amobarbital

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

            • atropine

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

            • atropine IV/IM

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

            • bazedoxifene/conjugated estrogens

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

            • brimonidine

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

            • butabarbital

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

            • chlorpromazine

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

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

            • chlorpropamide

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

            • conjugated estrogens

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

            • desflurane

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

            • dexmethylphenidate

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

            • diphenhydramine

              diphenhydramine will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • dronedarone

              dronedarone will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • duloxetine

              duloxetine will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • estradiol

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

            • estropipate

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

            • ethinylestradiol

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

            • etomidate

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

            • eucalyptus

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

            • fluphenazine

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

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

            • glimepiride

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

            • glipizide

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

            • glyburide

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

            • hydroxyprogesterone caproate

              hydroxyprogesterone caproate, doxepin. 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

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

            • insulin detemir

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

            • insulin glargine

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

            • insulin glulisine

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

            • insulin lispro

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

            • insulin NPH

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

            • insulin regular human

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

            • isoproterenol

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

            • ketamine

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

            • lithium

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

            • maraviroc

              maraviroc will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • marijuana

              marijuana will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • mestranol

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

            • metformin

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

            • miglitol

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

            • nateglinide

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

            • panax ginseng

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

            • parecoxib

              parecoxib will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • pentobarbital

              pentobarbital, doxepin. 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

              perphenazine will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

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

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

            • phenobarbital

              phenobarbital, doxepin. 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

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

            • pleurisy root

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

            • primidone

              primidone, doxepin. 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

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

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

            • progesterone micronized

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

            • promazine

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

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

            • promethazine

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

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

            • propofol

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

            • quinacrine

              quinacrine will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • ranolazine

              ranolazine will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • repaglinide

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

            • rosiglitazone

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

            • sage

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

            • saxagliptin

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

            • secobarbital

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

            • serdexmethylphenidate/dexmethylphenidate

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

            • sertraline

              sertraline will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • sevoflurane

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

            • sitagliptin

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

            • sulfamethoxazole

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

            • thioridazine

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

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

            • tipranavir

              tipranavir will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

            • tolazamide

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

            • tolbutamide

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

            • trifluoperazine

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

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

            • vasopressin

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

            • verapamil

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

            • vildagliptin

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

            • zolpidem

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

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            Adverse Effects

            Frequency Not Defined

            Sedation, fatigue, weakness, lethargy

            Dry mouth

            Constipation

            Blurred vision

            Headache

            Agitation

            Insomnia

            Anxiety

            Nausea, vomiting

            Sweating

            Confusion, extrapyramidal symptoms (EPS), dizziness, paresthesia

            Orthostatic hypotension, ECG changes, tachycardia

            Increased LFTs

            Tinnitus

            Sexual dysfunction

            Rash

            Seizure

            Agranulocytosis

            Thrombocytopenia

            Eosinophilia

            Leukopenia

            SIADH

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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 >24 years; a slight decrease in suicidal thinking was seen in adults >65 years

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

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

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

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

            This drug is not approved for use in pediatric patients

            Contraindications

            Hypersensitivity

            Untreated narrow-angle glaucoma

            Severe urinary retention

            Within 14 days of MAO inhibitors

            Cautions

            Use caution in BPH, urinary retention, decreased GI motility, hyperthyroidism, brain tumor, diabetes, hepatic impairment, cardiovascular disease, mania/hypomania, respiratory disease, and seizure disorders

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

            Risk of anticholinergic side effects

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

            CNS depressant; can impair alertness and motor coordination; avoid use with other CNS depressants (eg, alcohol)

            Overdose may cause EKG QRS widening and risk of dysrhythmias

            Protect capsules and oral concentrate from direct sunlight

            Prescriptions should be written for smallest quantity consistent with good patient care; patient's family or caregiver should alert healthcare professional about emergence of suicidality and related behaviors including agitation, panic attacks, irritability, impulsivity, mania, and insomnia or if worsening depression or psychosis occurs

            Anticholinergic effects including blurred vision, urinary retention, xerostomia, and constipation may occur

            Neuropsychiatric symptoms may occur unpredictably including anxiety and psychosis

            Bone fracture reported with use of antidepressant therapy; consider possibility of fracture if patient presents with unexplained bone pain, joint tenderness, bruising or swelling

            May cause orthostatic hypotension; use caution in patients at risk of this effect or that may not tolerate hypotensive episodes (eg, hypovolemia, cardiovascular or cerebrovascular disease and others)

            Sleep related activities including sleep driving, eating food, cooking, making phone calls reported; discontinue therapy if patient reports sleep-related episodes

            Possibility of EPS and neuroleptic malignant syndrome (NMS)

            May cause confusion in the elderly; avoid doses >6 mg/day

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            Pregnancy & Lactation

            Pregnancy

            Available data from published epidemiologic studies and postmarketing reports have not established increased risk of major birth defects or miscarriage; there are risks of poor neonatal adaptation with exposure to drug during pregnancy

            Neonatal adverse effects

            • Neonates exposed to TCAs, including doxepin, late in third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding; such complications can arise immediately upon delivery
            • Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hyperreflexia, tremor, jitteriness, irritability and constant crying. These findings are consistent with either direct toxic effects of TCAs or possibly a drug discontinuation syndrome
            • Monitor neonates who were exposed to drug in third trimester of pregnancy for poor neonatal adaptation syndrome

            Animal data

            • Based on results from animal fertility studies conducted in rats, doxepin may reduce fertility in females and males of reproductive potential
            • In animal reproduction studies, oral administration of doxepin to rats and rabbits during period of organogenesis caused adverse developmental effects at doses 65 and 23 times maximum recommended human dose (MRHD) of 6 mg/day based on AUC, respectively
            • Oral administration to pregnant rats during pregnancy and lactation resulted in decreased pup survival and a delay in pup growth at doses 60 times MRHD based on AUC

            Lactation

            Data from published report presence of drug and metabolite in human milk; there are reports of excess sedation, respiratory depression, poor sucking and swallowing, and hypotonia in breastfed infants exposed to drug

            There are no data on effects of drug on milk production; because of potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during therapy

            Infants exposed to drug through breast milk should be monitored for excess sedation, respiratory depression and hypotonia

            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

            Exact mechanism for doxepin's sleep maintenance effect is unknown; however, doxepin's action is believed to result from antagonism of the histamine H1 receptor

            Mechanism of action for depression is unknown; may increase CNS synaptic concentrations of serotonin and norepinephrine by inhibiting reuptake

            Absorption

            Peak plasma time: 2 hr

            Onset: >2 weeks (depression)

            Distribution

            Protein bound: 80%

            Metabolism

            Hepatic CYP2D6, CYP2C19

            Metabolites: N-demethyldoxepin

            Elimination

            Half-life: 6-8 hr

            Excretion: Urine

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            doxepin oral
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            doxepin oral
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            doxepin oral
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            doxepin oral
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            doxepin oral
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            doxepin oral
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            doxepin oral
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            10 mg capsule
            Silenor oral
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            6 mg tablet
            Silenor oral
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            3 mg tablet
            doxepin topical
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            5 % cream

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            Patient Handout

            Select a drug:
            Patient Education
            doxepin oral

            DOXEPIN (SLEEP) - ORAL

            (dox-EH-pin)

            COMMON BRAND NAME(S): Silenor

            USES: This medication is used to treat a certain sleep problem (insomnia). It may help you stay asleep longer and reduce the number of times you awaken during the night. Doxepin belongs to a class of drugs known as tricyclic antidepressants. It is not known how this medication improves sleep, though it may be due to blocking histamine receptors.

            HOW TO USE: Read the Medication Guide provided by your pharmacist before you start taking doxepin and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth, usually once nightly within 30 minutes before bedtime on an empty stomach, or as directed by your doctor. Do not take it within 3 hours of a meal because the effect of the medication will be delayed.Do not take this medication unless you are able to get a full night of sleep (7-8 hours) before you must be active again.Dosage is based on your medical condition, age, and response to therapy. Do not take more than 6 milligrams per day.Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day.Tell your doctor if your condition lasts or gets worse after 7-10 days.

            SIDE EFFECTS: Drowsiness or nausea may occur. If either of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Rarely, after taking this drug, people have gotten out of bed and driven vehicles while not fully awake ("sleep-driving"). People have also sleepwalked, prepared/eaten food, made phone calls, or had sex while not fully awake. Often, these people do not remember these events. This problem can be dangerous to you or to others. If you find out that you have done any of these activities after taking this medication, tell your doctor right away. Your risk is increased if you use alcohol or other medications that can make you drowsy while taking doxepin.At higher doses, doxepin is used to treat a variety of other conditions, including depression and other mental/mood disorders. It can help prevent suicidal thoughts/attempts and provide other important benefits. However, studies have shown that a small number of people (especially people younger than 25) who take antidepressants for any condition may experience worsening depression, other mental/mood symptoms, or suicidal thoughts/attempts. It is very important to talk with the doctor about the risks and benefits of antidepressant medication (especially for people younger than 25), even if treatment is not for a mental/mood condition. Tell the doctor right away if you notice worsening depression/other psychiatric conditions, unusual behavior changes (including possible suicidal thoughts/attempts), or other mental/mood changes (including new/worsening anxiety, panic attacks, irritability, hostile/angry feelings, impulsive actions, severe restlessness, very rapid speech). Be especially watchful for these symptoms if a new antidepressant is started or when the dose is changed.Get medical help right away if you have any very serious side effects, including: eye pain/swelling/redness, widened pupils, vision changes (such as seeing rainbows around lights at night, blurred vision).A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

            PRECAUTIONS: Before taking doxepin, tell your doctor or pharmacist if you are allergic to it; or to other tricyclic antidepressants (such as amoxapine); 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: problems urinating (urinary retention), personal or family history of glaucoma (angle-closure type).This drug may make you drowsy. Alcohol or marijuana (cannabis) can make you more drowsy. Do not drive, use machinery, or do anything that needs alertness 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).During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor. Babies born to mothers who have used this drug during the last 3 months of pregnancy may rarely develop withdrawal symptoms such as feeding/breathing difficulties, seizures, muscle stiffness, or constant crying. If you notice any of these symptoms in your newborn, tell the doctor promptly.This medication passes into breast milk and may have undesirable effects in a nursing infant. Breast-feeding while using this drug is not recommended. 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: cimetidine.Taking MAO inhibitors with this medication may cause a serious (possibly fatal) drug interaction. Avoid taking MAO inhibitors (isocarboxazid, linezolid, metaxalone, methylene blue, moclobemide, phenelzine, procarbazine, rasagiline, safinamide, selegiline, tranylcypromine) during treatment with this medication. Most MAO inhibitors should also not be taken for two weeks before and after treatment with this medication. Ask your doctor when to start or stop taking this medication.Tell your doctor or pharmacist if you are taking other products that cause drowsiness such as opioid pain or cough relievers (such as codeine, hydrocodone), alcohol, marijuana (cannabis), other drugs for sleep or anxiety (such as alprazolam, lorazepam, zolpidem), muscle relaxants (such as carisoprodol, cyclobenzaprine), or antihistamines (such as cetirizine, diphenhydramine).Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

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

            NOTES: Do not share this medication with others.This medication has been prescribed for your current condition only. Do not use it later for other conditions unless directed by your doctor. A different medication may be necessary in those cases.Usually, insomnia is temporary and requires sleep medications only for a short time. If you require treatment for more than 7-10 days, laboratory and/or medical tests should be performed to find the cause of your sleep problem.As you get older, your sleep pattern may naturally change and your sleep may be interrupted several times during the night. Talk to your doctor or pharmacist for ways to improve your sleep without medication, such as avoiding caffeine and alcohol close to bedtime, avoiding daytime naps, and avoiding going to bed too early each night.

            MISSED DOSE: If you miss a dose, take it as soon as you remember if it is still near bedtime and you have trouble falling asleep. If it is already the next day, take your next dose at the regular time that night at bedtime. Do not double the dose to catch up.

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

            Information last revised February 2022. Copyright(c) 2022 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.

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            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.