doxepin (Rx)

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

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 (157)

• 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.

• benzhydrocodone/acetaminophen

  benzhydrocodone/acetaminophen and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• 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.

• buprenorphine buccal

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

• buprenorphine subdermal implant

  buprenorphine subdermal implant and doxepin both increase QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine subdermal implant and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine transdermal

  buprenorphine transdermal and doxepin both increase QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine transdermal and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine, long-acting injection

  buprenorphine, long-acting injection and doxepin both increase QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine, long-acting injection and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• 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.

• fentanyl

  fentanyl and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl intranasal

  fentanyl intranasal and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl iontophoretic transdermal system

  fentanyl iontophoretic transdermal system and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl transdermal

  fentanyl transdermal and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl transmucosal

  fentanyl transmucosal and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• 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.

• givinostat

  doxepin and givinostat both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid coadministration, obtain ECGs when initiating, during concomitant use, and as clinically indicated. Withhold if QTc interval >500 ms or a change from baseline >60 ms.

• 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.

• methohexital

  methohexital and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• 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.

• olopatadine intranasal

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

• ondansetron

  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.

• zuranolone

  doxepin, zuranolone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration of zuranolone with other CNS depressants may increase impairment of psychomotor performance or CNS depressant effects. If unavoidable, consider dose reduction. .

Monitor Closely (392)

• 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

  doxepin increases effects of abobotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Drugs with anticholinergic effects may potentiate botulinum toxin effects, which may result in excessive neuromuscular weakness and heighten systemic anticholinergic effects.

• aclidinium

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

• acrivastine

  acrivastine and doxepin both increase sedation. 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.
  
  asenapine and doxepin both increase sedation. Use Caution/Monitor.

• asenapine transdermal

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

• avapritinib

  avapritinib and doxepin both increase sedation. 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.

• brexpiprazole

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

• brimonidine

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

• brivaracetam

  brivaracetam and doxepin both increase sedation. 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.

• cariprazine

  cariprazine 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 topical

  doxepin and cocaine topical 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.

• daxibotulinumtoxinA

  doxepin increases effects of daxibotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Drugs with anticholinergic effects may potentiate botulinum toxin effects, which may result in excessive neuromuscular weakness and heighten systemic anticholinergic effects.

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

• dexchlorpheniramine

  dexchlorpheniramine and 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.

• gepirone

  gepirone and doxepin both increase serotonin levels. Use Caution/Monitor. Monitor for symptoms of serotonin syndrome when gepirone is used gepirone with other drugs that may affect the serotonergic neurotransmitter systems. If serotonin syndrome occurs, consider discontinue gepirone and/or concomitant serotonergic drug.

• 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.

• icosapent

  icosapent, doxepin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Icosapent may prolong bleeding time. Periodically monitor if coadministered with other drugs that affect bleeding.

• 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.

• incobotulinumtoxinA

  doxepin increases effects of incobotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Drugs with anticholinergic effects may potentiate botulinum toxin effects, which may result in excessive neuromuscular weakness and heighten systemic anticholinergic effects.

• 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.

• letibotulinumtoxinA

  doxepin increases effects of letibotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Drugs with anticholinergic effects may potentiate botulinum toxin effects, which may result in excessive neuromuscular weakness and heighten systemic anticholinergic 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.

• levetiracetam

  levetiracetam and doxepin both increase sedation. 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.

• levothyroxine

  levothyroxine increases effects of doxepin by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• liothyronine

  liothyronine increases effects of doxepin by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• liotrix

  liotrix increases effects of doxepin by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• 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.

• methylphenidate transdermal

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

• midazolam

  midazolam and 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

• olanzapine/samidorphan

  doxepin, olanzapine/samidorphan. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of diazepam, alcohol, or other CNS acting drugs may potentiate orthostatic hypotension observed with olanzapine. Additive sedation may also occur.

• 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

  doxepin increases effects of onabotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Drugs with anticholinergic effects may potentiate botulinum toxin effects, which may result in excessive neuromuscular weakness and heighten systemic anticholinergic effects.

• 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.

• prabotulinumtoxinA

  doxepin increases effects of prabotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Drugs with anticholinergic effects may potentiate botulinum toxin effects, which may result in excessive neuromuscular weakness and heighten systemic anticholinergic effects.

• 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.

• rimabotulinumtoxinB

  doxepin increases effects of rimabotulinumtoxinB by pharmacodynamic synergism. Use Caution/Monitor. Drugs with anticholinergic effects may potentiate botulinum toxin effects, which may result in excessive neuromuscular weakness and heighten systemic anticholinergic effects.

• 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 chloride/magnesium sulfate/polyethylene glycol

  doxepin, sodium sulfate/potassium chloride/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.

• 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.

• 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.

• tetrabenazine

  tetrabenazine and doxepin both increase QTc interval. 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.

• thyroid desiccated

  thyroid desiccated increases effects of doxepin by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• 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.

• valbenazine

  valbenazine and doxepin both increase 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 (DSC)

  hydroxyprogesterone caproate (DSC), 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.

• 5-HTP

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

• abiraterone

  Monitor Closely (1)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

  Monitor Closely (1)doxepin increases effects of abobotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Drugs with anticholinergic effects may potentiate botulinum toxin effects, which may result in excessive neuromuscular weakness and heighten systemic anticholinergic effects.

• acarbose

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

• aclidinium

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

• acrivastine

  Monitor Closely (1)acrivastine and doxepin both increase sedation. Use Caution/Monitor.

• albuterol

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

• alfentanil

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

• alfuzosin

  Monitor Closely (1)doxepin and alfuzosin both increase QTc interval. Use Caution/Monitor.

• almotriptan

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

• alprazolam

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

• amifampridine

  Monitor Closely (1)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

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

• amisulpride

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

• amitriptyline

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

• amobarbital

  Monitor Closely (1)amobarbital and doxepin both increase sedation. Use Caution/Monitor.Minor (1)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.

• amoxapine

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

• anagrelide

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

• anticholinergic/sedative combos

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

• apomorphine

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

• arformoterol

  Monitor Closely (2)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.Serious - Use Alternative (1)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.

• aripiprazole

  Monitor Closely (2)aripiprazole and doxepin both increase sedation. Use Caution/Monitor.
  
  doxepin and aripiprazole both increase QTc interval. Use Caution/Monitor.

• armodafinil

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

• arsenic trioxide

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

• artemether

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

• artemether/lumefantrine

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

• asenapine

  Monitor Closely (3)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.
  
  asenapine and doxepin both increase sedation. Use Caution/Monitor.

• asenapine transdermal

  Monitor Closely (2)asenapine transdermal and doxepin both increase QTc interval. Use Caution/Monitor.
  
  asenapine transdermal and doxepin both increase sedation. Use Caution/Monitor.

• atazanavir

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

• atomoxetine

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

• atracurium

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

• atropine

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

• atropine IV/IM

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

• avapritinib

  Monitor Closely (1)avapritinib and doxepin both increase sedation. Use Caution/Monitor.

• azelastine

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

• azithromycin

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

• baclofen

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

• bazedoxifene/conjugated estrogens

  Minor (1)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.

• bedaquiline

  Monitor Closely (1)doxepin and bedaquiline both increase QTc interval. Use Caution/Monitor.

• belladonna alkaloids

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

• belladonna and opium

  Monitor Closely (2)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

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

• benzhydrocodone/acetaminophen

  Monitor Closely (1)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.Serious - Use Alternative (1)benzhydrocodone/acetaminophen and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• benzphetamine

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

• benztropine

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

• bethanechol

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

• brexpiprazole

  Monitor Closely (1)brexpiprazole and doxepin both increase sedation. Use Caution/Monitor.

• brimonidine

  Monitor Closely (1)brimonidine and doxepin both increase sedation. Use Caution/Monitor.Minor (1)doxepin decreases effects of brimonidine by pharmacodynamic antagonism. Minor/Significance Unknown.

• brivaracetam

  Monitor Closely (1)brivaracetam and doxepin both increase sedation. Use Caution/Monitor.

• brompheniramine

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

• buprenorphine

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

• buprenorphine buccal

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

• buprenorphine subdermal implant

  Monitor Closely (1)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.Serious - Use Alternative (2)buprenorphine subdermal implant and doxepin both increase QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine subdermal implant and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine transdermal

  Serious - Use Alternative (2)buprenorphine transdermal and doxepin both increase QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine transdermal and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• buprenorphine, long-acting injection

  Monitor Closely (1)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.Serious - Use Alternative (2)buprenorphine, long-acting injection and doxepin both increase QTc interval. Avoid or Use Alternate Drug.
  
  buprenorphine, long-acting injection and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• bupropion

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

• buspirone

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

• butabarbital

  Monitor Closely (1)butabarbital and doxepin both increase sedation. Use Caution/Monitor.Minor (1)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

  Monitor Closely (1)butalbital and doxepin both increase sedation. Use Caution/Monitor.Minor (1)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.

• butorphanol

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

• caffeine

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

• calcium/magnesium/potassium/sodium oxybates

  Serious - Use Alternative (1)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.

• carbachol

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

• carbamazepine

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

• carbinoxamine

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

• cariprazine

  Monitor Closely (1)cariprazine and doxepin both increase sedation. Use Caution/Monitor.

• carisoprodol

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

• celecoxib

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

• cenobamate

  Monitor Closely (2)cenobamate, doxepin. Either increases effects of the other by sedation. Use Caution/Monitor.
  
  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.

• ceritinib

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

• cevimeline

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

• chloral hydrate

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

• chlordiazepoxide

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

• chloroquine

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

• chlorpheniramine

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

• chlorpromazine

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

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

• chlorzoxazone

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

• cimetidine

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

• cinnarizine

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

• ciprofloxacin

  Monitor Closely (1)doxepin and ciprofloxacin both increase QTc interval. Use Caution/Monitor.

• cisatracurium

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

• citalopram

  Serious - Use Alternative (2)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

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

• clemastine

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

• clobazam

  Monitor Closely (2)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

  Monitor Closely (1)doxepin and clofazimine both increase QTc interval. Use Caution/Monitor.

• clomipramine

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

• clonazepam

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

• clonidine

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

• clorazepate

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

• clozapine

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

• cobicistat

  Monitor Closely (2)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 topical

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

• codeine

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

• conjugated estrogens

  Minor (1)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

  Minor (1)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.

• crizotinib

  Monitor Closely (1)doxepin and crizotinib both increase QTc interval. Use Caution/Monitor.

• cyclizine

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

• cyclobenzaprine

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

• cyproheptadine

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

• dabrafenib

  Monitor Closely (1)dabrafenib will decrease the level or effect of doxepin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely.

• dacomitinib

  Serious - Use Alternative (1)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.

• dantrolene

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

• daridorexant

  Monitor Closely (1)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

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

• dasatinib

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

• daxibotulinumtoxinA

  Monitor Closely (1)doxepin increases effects of daxibotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Drugs with anticholinergic effects may potentiate botulinum toxin effects, which may result in excessive neuromuscular weakness and heighten systemic anticholinergic effects.

• debrisoquine

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

• degarelix

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

• desflurane

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

• desipramine

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

  Monitor Closely (1)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 mgSerious - Use Alternative (1)doxepin and desvenlafaxine both increase serotonin levels. Avoid or Use Alternate Drug.

• deutetrabenazine

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

• dexchlorpheniramine

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

• dexfenfluramine

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

• dexmedetomidine

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

• dexmethylphenidate

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

• dextroamphetamine

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

• dextroamphetamine transdermal

  Monitor Closely (1)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.

• dextromethorphan

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

• dextromoramide

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

• diamorphine

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

• diazepam

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

• diazepam intranasal

  Monitor Closely (1)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

  Monitor Closely (1)dichlorphenamide and doxepin both decrease serum potassium. Use Caution/Monitor.

• dicyclomine

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

• diethylpropion

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

• difelikefalin

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

• difenoxin hcl

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

• dihydroergotamine

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

• dihydroergotamine intranasal

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

• dimenhydrinate

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

• diphenhydramine

  Monitor Closely (2)diphenhydramine and doxepin both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  diphenhydramine and doxepin both increase sedation. Use Caution/Monitor.Minor (1)diphenhydramine will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• diphenoxylate hcl

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

• dipipanone

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

• disopyramide

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

• dobutamine

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

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

• dolasetron

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

• donepezil

  Monitor Closely (2)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

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

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

• doxylamine

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

• dronedarone

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

• droperidol

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

• duloxetine

  Serious - Use Alternative (1)duloxetine and doxepin both increase serotonin levels. Avoid or Use Alternate Drug.Minor (1)duloxetine will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• echothiophate iodide

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

• efavirenz

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

• eletriptan

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

• eliglustat

  Monitor Closely (2)doxepin and eliglustat both increase QTc interval. Use Caution/Monitor.
  
  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.

• elvitegravir/cobicistat/emtricitabine/tenofovir DF

  Monitor Closely (1)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.

• encorafenib

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

• entrectinib

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

• ephedrine

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

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

  Monitor Closely (1)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

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

• ergotamine

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

• eribulin

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

• erythromycin base

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

• erythromycin ethylsuccinate

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

• erythromycin lactobionate

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

• erythromycin stearate

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

• escitalopram

  Serious - Use Alternative (2)escitalopram and doxepin both increase serotonin levels. Avoid or Use Alternate Drug.
  
  doxepin and escitalopram both increase QTc interval. Avoid or Use Alternate Drug.

• esketamine intranasal

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

• estazolam

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

• estradiol

  Minor (1)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

  Minor (1)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

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

• estropipate

  Minor (1)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

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

• ethinylestradiol

  Minor (1)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

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

• eucalyptus

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

• fedratinib

  Monitor Closely (2)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

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

• fentanyl

  Serious - Use Alternative (1)fentanyl and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl intranasal

  Serious - Use Alternative (1)fentanyl intranasal and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl iontophoretic transdermal system

  Serious - Use Alternative (1)fentanyl iontophoretic transdermal system and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl transdermal

  Serious - Use Alternative (1)fentanyl transdermal and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fentanyl transmucosal

  Serious - Use Alternative (1)fentanyl transmucosal and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• fesoterodine

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

• fexinidazole

  Serious - Use Alternative (2)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.

• fingolimod

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

• flavoxate

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

• flecainide

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

• fluconazole

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

• fluoxetine

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

• fluphenazine

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

• flurazepam

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

• fluvoxamine

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

• formoterol

  Monitor Closely (1)doxepin increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (2)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

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

• foscarnet

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

• fostemsavir

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

• frovatriptan

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

• gabapentin

  Monitor Closely (1)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

  Monitor Closely (1)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

  Monitor Closely (1)gadobenate and doxepin both increase QTc interval. Use Caution/Monitor.

• galantamine

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

• ganaxolone

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

• gemifloxacin

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

• gemtuzumab

  Monitor Closely (1)doxepin and gemtuzumab both increase QTc interval. Use Caution/Monitor.

• gepirone

  Monitor Closely (1)gepirone and doxepin both increase serotonin levels. Use Caution/Monitor. Monitor for symptoms of serotonin syndrome when gepirone is used gepirone with other drugs that may affect the serotonergic neurotransmitter systems. If serotonin syndrome occurs, consider discontinue gepirone and/or concomitant serotonergic drug.

• gilteritinib

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

• givinostat

  Serious - Use Alternative (1)doxepin and givinostat both increase QTc interval. Avoid or Use Alternate Drug. If unable to avoid coadministration, obtain ECGs when initiating, during concomitant use, and as clinically indicated. Withhold if QTc interval >500 ms or a change from baseline >60 ms.

• givosiran

  Serious - Use Alternative (1)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

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

• glimepiride

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

• glipizide

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

• glyburide

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

• glycopyrrolate

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

• glycopyrrolate inhaled

  Monitor Closely (2)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

  Monitor Closely (1)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

  Monitor Closely (1)doxepin and goserelin both increase QTc interval. Use Caution/Monitor.

• granisetron

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

• guanfacine

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

• haloperidol

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

• henbane

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

• histrelin

  Monitor Closely (1)doxepin and histrelin both increase QTc interval. Use Caution/Monitor.

• homatropine

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

• huperzine A

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

• hydrocodone

  Monitor Closely (1)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

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

• hydroxychloroquine sulfate

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

• hydroxyprogesterone caproate (DSC)

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

• hydroxyzine

  Monitor Closely (2)doxepin and hydroxyzine both increase QTc interval. Use Caution/Monitor.
  
  hydroxyzine and doxepin both increase sedation. Use Caution/Monitor.

• hyoscyamine

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

• hyoscyamine spray

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

• ibutilide

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

• icosapent

  Monitor Closely (1)icosapent, doxepin. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Icosapent may prolong bleeding time. Periodically monitor if coadministered with other drugs that affect bleeding.

• iloperidone

  Monitor Closely (3)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

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

• imipramine

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

• incobotulinumtoxinA

  Monitor Closely (1)doxepin increases effects of incobotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Drugs with anticholinergic effects may potentiate botulinum toxin effects, which may result in excessive neuromuscular weakness and heighten systemic anticholinergic effects.

• indacaterol, inhaled

  Monitor Closely (1)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.

• indapamide

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

• inotuzumab

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

• insulin aspart

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

• insulin detemir

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

• insulin glargine

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

• insulin glulisine

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

• insulin lispro

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

• insulin NPH

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

• insulin regular human

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

• iobenguane I 123

  Contraindicated (1)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.

• iobenguane I 131

  Serious - Use Alternative (1)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.

• ipratropium

  Monitor Closely (1)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.

• isocarboxazid

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

• isoflurane

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

• isoniazid

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

• isoproterenol

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

• istradefylline

  Monitor Closely (1)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

  Monitor Closely (1)itraconazole and doxepin both increase QTc interval. Use Caution/Monitor.

• ivosidenib

  Serious - Use Alternative (1)doxepin and ivosidenib both decrease QTc interval. Avoid or Use Alternate Drug.

• ketamine

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

• ketoconazole

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

• ketotifen, ophthalmic

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

• L-tryptophan

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

• lapatinib

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

• lasmiditan

  Monitor Closely (2)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

  Contraindicated (1)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.Monitor Closely (1)doxepin and lefamulin both increase QTc interval. Use Caution/Monitor.

• lemborexant

  Monitor Closely (1)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.

• lenvatinib

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

• letibotulinumtoxinA

  Monitor Closely (1)doxepin increases effects of letibotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Drugs with anticholinergic effects may potentiate botulinum toxin effects, which may result in excessive neuromuscular weakness and heighten systemic anticholinergic effects.

• leuprolide

  Monitor Closely (1)doxepin and leuprolide both increase QTc interval. Use Caution/Monitor.

• levalbuterol

  Monitor Closely (2)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.Serious - Use Alternative (1)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.

• levetiracetam

  Monitor Closely (1)levetiracetam and doxepin both increase sedation. Use Caution/Monitor.

• levofloxacin

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

• levoketoconazole

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

• levomilnacipran

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

• levorphanol

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

• levothyroxine

  Monitor Closely (1)levothyroxine increases effects of doxepin by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• linezolid

  Serious - Use Alternative (1)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.

• liothyronine

  Monitor Closely (1)liothyronine increases effects of doxepin by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• liotrix

  Monitor Closely (1)liotrix increases effects of doxepin by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• lisdexamfetamine

  Monitor Closely (2)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).
  
  doxepin increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.Serious - Use Alternative (1)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.

• lithium

  Monitor Closely (2)doxepin and lithium both increase QTc interval. Use Caution/Monitor.
  
  doxepin and lithium both increase serotonin levels. Modify Therapy/Monitor Closely.Minor (1)lithium, doxepin. Other (see comment). Minor/Significance Unknown. Comment: Risk of neurotoxicity in geriatric pts. Multiple mechanisms involved.

• lofepramine

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

• lofexidine

  Monitor Closely (3)doxepin decreases effects of lofexidine by unspecified interaction mechanism. Use Caution/Monitor.
  
  doxepin and lofexidine both increase QTc interval. Use Caution/Monitor.
  
  doxepin and lofexidine both increase sedation. Use Caution/Monitor.

• loperamide

  Monitor Closely (1)doxepin and loperamide both increase QTc interval. Use Caution/Monitor.

• lopinavir

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

• loprazolam

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

• lorazepam

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

• lorcaserin

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

• lormetazepam

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

• loxapine

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

• loxapine inhaled

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

• lsd

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

• lumefantrine

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

• lurasidone

  Monitor Closely (1)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.

• macimorelin

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

• maprotiline

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

• maraviroc

  Minor (1)maraviroc will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• marijuana

  Monitor Closely (1)doxepin and marijuana both increase sedation. Use Caution/Monitor.Minor (1)marijuana will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• meclizine

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

• mefloquine

  Serious - Use Alternative (1)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.

• melatonin

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

• meperidine

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

• meprobamate

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

• mestranol

  Minor (1)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.

• metaproterenol

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

• metaxalone

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

• metformin

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

• methadone

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

• methamphetamine

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

• methocarbamol

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

• methohexital

  Serious - Use Alternative (1)methohexital and doxepin both increase sedation. Avoid or Use Alternate Drug. Limit use to patients for whom alternative treatment options are inadequate

• methscopolamine

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

• methylene blue

  Serious - Use Alternative (1)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

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

• methylphenidate

  Monitor Closely (1)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.

• methylphenidate transdermal

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

• metoclopramide intranasal

  Serious - Use Alternative (1)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.

• midazolam

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

• midazolam intranasal

  Monitor Closely (1)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

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

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

• mifepristone

  Monitor Closely (1)doxepin and mifepristone both increase QTc interval. Use Caution/Monitor.

• miglitol

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

• milnacipran

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

• mirabegron

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

• mirtazapine

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

• mitotane

  Monitor Closely (1)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

  Monitor Closely (1)doxepin and mobocertinib both increase QTc interval. Use Caution/Monitor.

• modafinil

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

• morphine

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

• motherwort

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

• moxifloxacin

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

• moxonidine

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

• nabilone

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

• nalbuphine

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

• naratriptan

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

• nateglinide

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

• nefazodone

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

• nefopam

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

• neostigmine

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

• netupitant/palonosetron

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

• nilotinib

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

• norepinephrine

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

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

• octreotide

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

• octreotide (Antidote)

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

• ofloxacin

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

• olanzapine

  Monitor Closely (2)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
  
  olanzapine and doxepin both increase sedation. Use Caution/Monitor.

• olanzapine/samidorphan

  Monitor Closely (1)doxepin, olanzapine/samidorphan. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of diazepam, alcohol, or other CNS acting drugs may potentiate orthostatic hypotension observed with olanzapine. Additive sedation may also occur.

• oliceridine

  Monitor Closely (2)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

  Monitor Closely (1)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

• olopatadine intranasal

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

• onabotulinumtoxinA

  Monitor Closely (1)doxepin increases effects of onabotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Drugs with anticholinergic effects may potentiate botulinum toxin effects, which may result in excessive neuromuscular weakness and heighten systemic anticholinergic effects.

• ondansetron

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

• opium tincture

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

• orphenadrine

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

• osilodrostat

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

• osimertinib

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

• oxaliplatin

  Monitor Closely (1)doxepin and oxaliplatin both increase QTc interval. Use Caution/Monitor.

• oxazepam

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

• oxybutynin

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

• oxybutynin topical

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

• oxybutynin transdermal

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

• oxycodone

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

• oxymetazoline intranasal

  Monitor Closely (1)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

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

• ozanimod

  Serious - Use Alternative (2)doxepin and ozanimod both increase QTc interval. Contraindicated.
  
  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.

• paliperidone

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

• palonosetron

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

• panax ginseng

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

• pancuronium

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

• panobinostat

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

• papaveretum

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

• papaverine

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

• parecoxib

  Minor (1)parecoxib will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• paroxetine

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

• pasireotide

  Monitor Closely (1)doxepin and pasireotide both increase QTc interval. Use Caution/Monitor.

• pazopanib

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

• peginterferon alfa 2b

  Monitor Closely (1)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.

• pentamidine

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

• pentazocine

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

• pentobarbital

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

  Monitor Closely (1)perphenazine and doxepin both increase sedation. Use Caution/Monitor.Serious - Use Alternative (1)perphenazine and doxepin both increase QTc interval. Avoid or Use Alternate Drug.Minor (3)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.

• phendimetrazine

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

• phenelzine

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

• phenobarbital

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

• phentermine

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

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

  Monitor Closely (1)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

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

• pholcodine

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

• physostigmine

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

• pilocarpine

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

• pimavanserin

  Monitor Closely (1)doxepin and pimavanserin both increase QTc interval. Use Caution/Monitor.

• pimozide

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

• pioglitazone

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

• pirbuterol

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

  Serious - Use Alternative (2)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.

• pleurisy root

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

• ponesimod

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

• posaconazole

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

• prabotulinumtoxinA

  Monitor Closely (1)doxepin increases effects of prabotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Drugs with anticholinergic effects may potentiate botulinum toxin effects, which may result in excessive neuromuscular weakness and heighten systemic anticholinergic effects.

• pralidoxime

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

• pregabalin

  Monitor Closely (1)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.

• primaquine

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

• primidone

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

• procainamide

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

• procarbazine

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

• prochlorperazine

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

  Minor (1)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

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

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

• propafenone

  Monitor Closely (2)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

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

• propofol

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

• propylhexedrine

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

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

• pseudoephedrine

  Serious - Use Alternative (1)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.

• pyridostigmine

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

• quazepam

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

• quetiapine

  Monitor Closely (2)quetiapine and doxepin both increase sedation. Use Caution/Monitor.
  
  doxepin and quetiapine both increase QTc interval. Use Caution/Monitor.

• quinacrine

  Minor (1)quinacrine will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• quinidine

  Contraindicated (1)quinidine and doxepin both increase QTc interval. Contraindicated.Serious - Use Alternative (1)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

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

• ramelteon

  Monitor Closely (2)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

  Monitor Closely (1)doxepin and ranolazine both increase QTc interval. Modify Therapy/Monitor Closely.Minor (1)ranolazine will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• rapacuronium

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

• rasagiline

  Serious - Use Alternative (1)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.

• remifentanil

  Monitor Closely (1)doxepin, remifentanil. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. May also increase risk of serotonin syndrome.

• remimazolam

  Monitor Closely (1)remimazolam, 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.

• repaglinide

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

• ribociclib

  Serious - Use Alternative (2)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.

• rifabutin

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

• rilpivirine

  Monitor Closely (1)doxepin and rilpivirine both increase QTc interval. Use Caution/Monitor.

• rimabotulinumtoxinB

  Monitor Closely (1)doxepin increases effects of rimabotulinumtoxinB by pharmacodynamic synergism. Use Caution/Monitor. Drugs with anticholinergic effects may potentiate botulinum toxin effects, which may result in excessive neuromuscular weakness and heighten systemic anticholinergic effects.

• risperidone

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

• ritonavir

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

• rivastigmine

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

• rizatriptan

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

• rocuronium

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

• rolapitant

  Monitor Closely (1)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

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

• rosiglitazone

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

• safinamide

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

• sage

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

• salmeterol

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

• SAMe

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

• saquinavir

  Monitor Closely (1)doxepin and saquinavir both increase QTc interval. Use Caution/Monitor.

• saxagliptin

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

• scopolamine

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

• scullcap

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

• secobarbital

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

• selegiline

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

• selegiline transdermal

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

• selinexor

  Serious - Use Alternative (1)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.

• selpercatinib

  Monitor Closely (1)doxepin and selpercatinib both increase QTc interval. Use Caution/Monitor.

• serdexmethylphenidate/dexmethylphenidate

  Serious - Use Alternative (1)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.Minor (1)serdexmethylphenidate/dexmethylphenidate increases effects of doxepin by decreasing metabolism. Minor/Significance Unknown.

• sertraline

  Serious - Use Alternative (2)sertraline and doxepin both increase serotonin levels. Avoid or Use Alternate Drug.
  
  doxepin and sertraline both increase QTc interval. Avoid or Use Alternate Drug.Minor (1)sertraline will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• sevoflurane

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

• shepherd's purse

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

• siponimod

  Monitor Closely (1)doxepin and siponimod both increase QTc interval. Use Caution/Monitor.

• sitagliptin

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

• sodium oxybate

  Serious - Use Alternative (1)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.

• sodium sulfate/?magnesium sulfate/potassium chloride

  Monitor Closely (1)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 chloride/magnesium sulfate/polyethylene glycol

  Monitor Closely (1)doxepin, sodium sulfate/potassium chloride/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.

• sodium sulfate/potassium sulfate/magnesium sulfate

  Monitor Closely (1)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.

• solifenacin

  Monitor Closely (2)solifenacin and doxepin both decrease cholinergic effects/transmission. Use Caution/Monitor.
  
  doxepin and solifenacin both increase QTc interval. Use Caution/Monitor.

• sorafenib

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

• sotalol

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

• St John's Wort

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

• stiripentol

  Monitor Closely (2)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.
  
  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.

• succinylcholine

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

• sufentanil

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

• sufentanil SL

  Monitor Closely (1)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

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

• sumatriptan

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

• sumatriptan intranasal

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

• sunitinib

  Monitor Closely (1)doxepin and sunitinib both increase QTc interval. Use Caution/Monitor.

• suvorexant

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

• tacrolimus

  Monitor Closely (1)doxepin and tacrolimus both increase QTc interval. Use Caution/Monitor.

• tapentadol

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

• tedizolid

  Serious - Use Alternative (1)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.

• telavancin

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

• temazepam

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

• terbinafine

  Monitor Closely (1)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

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

• teriflunomide

  Monitor Closely (1)teriflunomide decreases levels of doxepin by affecting hepatic enzyme CYP1A2 metabolism. Use Caution/Monitor.

• tetrabenazine

  Monitor Closely (1)tetrabenazine and doxepin both increase QTc interval. Use Caution/Monitor.

• thioridazine

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

• thiothixene

  Monitor Closely (2)thiothixene and doxepin both increase sedation. Use Caution/Monitor.
  
  doxepin and thiothixene both increase QTc interval. Use Caution/Monitor.

• thyroid desiccated

  Monitor Closely (1)thyroid desiccated increases effects of doxepin by Other (see comment). Use Caution/Monitor. Comment: Increased catecholamine receptor sensitivity; may increase CNS and cardiovascular effects, including arrhythmias.

• tiotropium

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

• tipranavir

  Minor (1)tipranavir will increase the level or effect of doxepin by affecting hepatic enzyme CYP2D6 metabolism. Minor/Significance Unknown.

• tolazamide

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

• tolbutamide

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

• tolterodine

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

• topiramate

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

• toremifene

  Serious - Use Alternative (1)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.

• tramadol

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

• tranylcypromine

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

• trazodone

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

• triazolam

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

• triclabendazole

  Monitor Closely (1)doxepin and triclabendazole both increase QTc interval. Use Caution/Monitor.

• triclofos

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

• trifluoperazine

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

• trihexyphenidyl

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

• trimethoprim

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

• trimipramine

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

• triprolidine

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

• triptorelin

  Monitor Closely (1)doxepin and triptorelin both increase QTc interval. Use Caution/Monitor.

• tropisetron

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

• trospium chloride

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

• tucatinib

  Serious - Use Alternative (1)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

  Monitor Closely (1)doxepin and umeclidinium bromide/vilanterol inhaled both decrease QTc interval. Use Caution/Monitor.Serious - Use Alternative (1)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

• valbenazine

  Monitor Closely (1)valbenazine and doxepin both increase QTc interval. Use Caution/Monitor.

• valerian

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

• vandetanib

  Serious - Use Alternative (1)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.

• vardenafil

  Monitor Closely (1)doxepin and vardenafil both increase QTc interval. Use Caution/Monitor.

• vasopressin

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

• vecuronium

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

• vemurafenib

  Monitor Closely (1)doxepin and vemurafenib both increase QTc interval. Use Caution/Monitor.

• venlafaxine

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

• verapamil

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

• vilanterol/fluticasone furoate inhaled

  Serious - Use Alternative (1)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

  Serious - Use Alternative (1)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. .

• vildagliptin

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

• voclosporin

  Monitor Closely (1)doxepin and voclosporin both increase QTc interval. Use Caution/Monitor.

• voriconazole

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

• vorinostat

  Monitor Closely (1)doxepin and vorinostat both increase QTc interval. Use Caution/Monitor.

• vortioxetine

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

• xylometazoline

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

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

• yohimbine

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

• ziconotide

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

• ziprasidone

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

• zolmitriptan

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

• zolpidem

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

• zuranolone

  Serious - Use Alternative (1)doxepin, zuranolone. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration of zuranolone with other CNS depressants may increase impairment of psychomotor performance or CNS depressant effects. If unavoidable, consider dose reduction. .