pharmacopeia
GET
/api/v1/drug/doxepin
2D structure
3-(6H-benzo[c][1]benzoxepin-11-ylidene)-N,N-dimethylpropan-1-amine
SMILES CN(C)CCC=C1C2=CC=CC=C2COC3=CC=CC=C31
InChIKey ODQWQRRAPPTVAG-UHFFFAOYSA-N

Mechanism of action

Sourced from openFDA

The mechanism of action of doxepin in sleep maintenance is unclear; however, doxepin’s effect could be mediated through antagonism of the H1 receptor.

Monoamine OxidaseNorepinephrine UptakeSerotonin Uptake

Indications

Sourced from openFDA
  • Doxepin tablets are indicated for the treatment of insomnia characterized by difficulty with sleep maintenance. The clinical trials performed in support of efficacy were up to 3 months in duration.ICD-10: G47.00

Contraindications

Sourced from openFDA
  • Hypersensitivity to doxepin hydrochloride, inactive ingredients, or other dibenzoxepines. ( 4.1 ) Co-administration with Monoamine Oxidase Inhibitors (MAOIs): Do not administer if patient is taking MAOIs or has used MAOIs within the past two weeks.contraindicated

Dosage & administration

Sourced from openFDA

The dose of doxepin tablets should be individualized. Initial dose: 6 mg, once daily for adults ( 2.1 ) and 3 mg, once daily for the elderly. ( 2.1 , 2.2 ) Take within 30 minutes of bedtime. Total daily dose should not exceed 6 mg. ( 2.3 ) Should not be taken within 3 hours of a meal. ( 2.3 , 12.3 ) 2.1 Dosing in Adults The recommended dose of doxepin tablets for adults is 6 mg once daily. A 3 mg once daily dose may be appropriate for some patients, if clinically indicated. 2.2 Dosing in the Elderly The recommended starting dose of doxepin tablets in elderly patients (≥65 years old) is 3 mg once daily. The daily dose can be increased to 6 mg, if clinically indicated. 2.3 Administration Doxepin tablets should be taken within 30 minutes of bedtime. To minimize the potential for next day effects, doxepin tablets should not be taken within 3 hours of a meal [ see Clinical Pharmacology (12.3) ]. The total doxepin tablets dose should not exceed 6 mg per day.

Warnings & precautions

Sourced from openFDA

Need to Evaluate for Co-morbid Diagnoses: Reevaluate if insomnia persists after 7 to 10 days of use. ( 5.1 ) Abnormal thinking, behavioral changes, complex behaviors: May include “Sleep-driving” and hallucinations. Immediately evaluate any new onset behavioral changes. ( 5.2 ) Depression: Worsening of depression or suicidal thinking may occur. Prescribe the least amount feasible to avoid intentional overdose. ( 5.3 ) CNS-depressant effects: Use can impair alertness and motor coordination. Avoid engaging in hazardous activities such as operating a motor vehicle or heavy machinery after taking drug. ( 5.4 ) Do not use with alcohol. ( 5.4 , 7.3 ) Potential additive effects when used in combination with CNS depressants or sedating antihistamines. Dose reduction may be needed. ( 5.4 , 7.4 ) Patients with severe sleep apnea: Doxepin is ordinarily not recommended for use in this population. ( 8.7 ) 5.1 Need to Evaluate for Comorbid Diagnoses Because sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder, symptomatic treatment of insomnia should be initiated only after careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated. Exacerbation of insomnia or the emergence of new cognitive or behavioral abnormalities may be the consequence of an unrecognized psychiatric or physical disorder. Such findings have emerged during the course of treatment with hypnotic drugs.

Adverse reactions

Sourced from openFDA

The following serious adverse reactions are discussed in greater detail in other sections of labeling: Abnormal thinking and behavioral changes [see Warnings and Precautions (5.2)] . Suicide risk and worsening of depression [ see Warnings and Precautions (5.3) ] . CNS Depressant effects [ see Warnings and Precautions (5.4) ] . The most common treatment-emergent adverse reactions, reported in ≥ 2% of patients treated with doxepin, and more commonly than in patients treated with placebo, were somnolence/sedation, nausea, and upper respiratory tract infection. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Novadoz Pharmaceuticals LLC at 1-855-668-2369 and or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience The pre-marketing development program for doxepin tablets included doxepin HCl exposures in 1017 subjects (580 insomnia patients and 437 healthy subjects) from 12 studies conducted in the United States. 863 of these subjects (580 insomnia patients and 283 healthy subjects) participated in six randomized, placebo-controlled efficacy studies with doxepin doses of 1 mg, 3 mg, and 6 mg for up to 3-months in duration. Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Use in specific populations

Sourced from openFDA

Pregnancy: Third trimester use may increase the risk for symptoms of poor adaptation (respiratory distress, temperature instability, feeding difficulties, hypotonia, tremor, irritability) in the neonate. ( 8.1 ) Lactation: Breastfeeding not recommended. ( 8.2 ) Pediatric Use: Safety and effectiveness have not been evaluated. ( 8.4 ) Geriatric Use: The recommended starting dose is 3 mg. Monitor prior to considering dose escalation. ( 2.2 , 8.5 ) Use in Patients with Comorbid Illness: Initiate treatment with 3 mg in patients with hepatic impairment or tendency to urinary retention. ( 8.6 , 4.3 ) 8.1 Pregnancy Risk Summary Available data from published epidemiologic studies and postmarketing reports have not established an increased risk of major birth defects or miscarriage (see Data). There are risks of poor neonatal adaptation with exposure to tricyclic antidepressants (TCAs), including doxepin, during pregnancy (see Clinical Considerations). In animal reproduction studies, oral administration of doxepin to rats and rabbits during the period of organogenesis caused adverse developmental effects at doses 65 and 23 times the maximum recommended human dose (MRHD) of 6 mg/day based on AUC, respectively.

Pharmacokinetics

Sourced from openFDA
Metabolism
Absorption The median time to peak concentrations (T max ) of doxepin occurred at 3.5 hours postdose after oral administration of a 6 mg dose to fasted healthy subjects. Peak plasma concentrations (C max ) of doxepin increased in approximately a dose-proportional manner for 3 mg and 6 mg doses.

Overdosage

Sourced from openFDA

Doxepin is routinely administered for indications other than insomnia at doses 10- to 50-fold higher than the highest recommended dose of doxepin. The signs and symptoms associated with doxepin use at doses several-fold higher than the maximum recommended dose (Excessive dose) of doxepin for the treatment of insomnia are described [ see Overdosage (10.1) ], as are signs and symptoms associated with higher multiples of the maximum recommended dose (Critical overdose) [ see Overdosage (10.2) ]. 10.1 Signs and Symptoms of Excessive Doses The following adverse effects have been associated with use of doxepin at doses higher than 6 mg. Anticholinergic Effects : constipation and urinary retention. Central Nervous System : disorientation, hallucinations, numbness, paresthesias, extrapyramidal symptoms, seizures, tardive dyskinesia. Cardiovascular : hypotension. Gastrointestinal : aphthous stomatitis, indigestion. Endocrine : raised libido, testicular swelling, gynecomastia in males, enlargement of breasts and galactorrhea in the female, raising or lowering of blood sugar levels, and syndrome of inappropriate antidiuretic hormone secretion.

Approval history

Sourced from openFDA
  • May 13, 1986ANDAANDA070791Mylan Pharms Inc
  • Nov 9, 1987ANDAANDA071422Ph Health
  • Apr 1, 1994NDANDA020126Mylan
  • Dec 29, 1998ANDAANDA074721Lannett Co Inc
  • Mar 17, 2010NDANDA022036Currax
  • Jul 26, 2013ANDAANDA201951Actavis Elizabeth
  • Jan 20, 2016ANDAANDA202337Rk Pharma
  • Jun 28, 2017ANDAANDA207482Amneal Pharms Co

FAERS reports

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Reference statistics only. FAERS reports are voluntarily submitted and are not incidence rates, safety signals, or causal evidence. Counts reflect reporting volume — how often a reaction was reported, not how often it occurs. For decision-grade use, consult openFDA and the FAERS Public Dashboard directly.
12,345 total reports matchedLatest report Share = reports listing the reaction ÷ total matched reports. Rows can sum to >100% because a single report often lists multiple reactions.
  1. 1Drug Ineffective9848.0%
  2. 2Toxicity To Various Agents9838.0%
  3. 3Completed Suicide8246.7%
  4. 4Fatigue7806.3%
  5. 5Pain7496.1%
  6. 6Nausea6705.4%
  7. 7Headache6265.1%
  8. 8Insomnia6135.0%
  9. 9Off Label Use6004.9%
  10. 10Dizziness5924.8%
  11. 11Pruritus5924.8%
  12. 12Anxiety5654.6%
  13. 13Fall5654.6%
  14. 14Diarrhoea5454.4%
  15. 15Dyspnoea5264.3%

Literature

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Recent PubMed references pinned to Doxepin as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

Clinical trials

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The 10 most recently updated of 23 ClinicalTrials.gov registrations naming Doxepin as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

Pharmacogenomics

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CPIC-curated drug–gene pairs for Doxepin. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

Frequently asked questions

How does Doxepin work?
The mechanism of action of doxepin in sleep maintenance is unclear; however, doxepin’s effect could be mediated through antagonism of the H1 receptor.
What is Doxepin used for?
According to FDA labeling, Doxepin carries indications including: Doxepin tablets are indicated for the treatment of insomnia characterized by difficulty with sleep maintenance. The clinical trials performed in support of efficacy were up to 3 months in duration.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
What class of drug is Doxepin?
Doxepin is classified as Non-selective monoamine reuptake inhibitors, Other antipruritics, Tricyclic Antidepressant, Monoamine Oxidase Inhibitors, Norepinephrine Uptake Inhibitors, Serotonin Uptake Inhibitors, Decreased Serotonin Degradation, Increased Central Nervous System Norepinephrine Activity.
What are the brand names for Doxepin?
Doxepin is marketed under brand names including Prudoxin, Silenor, Zonalon.
What are the contraindications for Doxepin?
Doxepin labeling lists contraindications including: Hypersensitivity to doxepin hydrochloride, inactive ingredients, or other dibenzoxepines. ( 4.1 ) Co-administration with Monoamine Oxidase Inhibitors (MAOIs): Do not administer if patient is taking MAOIs or has used MAOIs within the past two weeks.. Always consult the full prescribing information and a clinician.
Note. Data for doxepin is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.

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