Doxepin binds with high affinity to the histamine H1 receptor (Ki<1 nM) where it functions as an antagonist. The exact mechanism by which doxepin exerts its sleep maintenance effect is unknown but is believed due to its antagonism of the H1 receptor.

Doxepin is 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.

Dosing in Adults: The recommended dose of Doxepin for adults is 6 mg once daily. A 3 mg once daily dose may be appropriate for some patients, if clinically indicated.

Dosing in the Elderly: The recommended starting dose of Doxepin in elderly patients (≥65 years old) is 3 mg once daily. The daily dose can be increased to 6 mg, if clinically indicated.

Administration: Doxepin should be taken within 30 minutes of bedtime. To minimize the potential for next day effects, Doxepin should not be taken within 3 hours of a meal. The total Doxepin dose should not exceed 6 mg per day.

Pediatric Use: The safety and effectiveness of Doxepin in pediatric patients have not been evaluated.

Hypersensitivity: Doxepin is contraindicated in individuals who have shown hypersensitivity to doxepin HCl,

any of its inactive ingredients, or other dibenoxepines.

Co-administration with Monoamine Oxidase Inhibitors (MAOIs): Serious side effects and even death have been reported following the concomitant use of certain drugs with MAO inhibitors. Do not administer Doxepin if patient is currently on MAOIs or has used MAOIs within the past two weeks. The exact length of time may vary depending on the particular MAOI dosage and duration of treatment.

Glaucoma and Urinary Retention: Doxepin is contraindicated in individuals with untreated narrow-angle glaucoma or severe urinary retention.

The following serious adverse reactions are as follows:

• Abnormal thinking and behavioral changes 
• Suicide risk and worsening of depression
• CNS Depressant effects

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.

Abnormal Thinking and Behavioral Changes: Complex behaviors such as “sleep-driving” (i.e., driving while not fully awake after ingestion of a hypnotic, with amnesia for the event) have been reported with hypnotics. These events can occur in hypnotic-naive as well as in hypnotic-experienced persons. Although behaviors such as "sleep-driving" may occur with hypnotics alone at therapeutic doses, the use of alcohol and other CNS depressants with hypnotics appears to increase the risk of such behaviors, as does the use of hypnotics at doses exceeding the maximum recommended dose. Due to the risk to the patient and the community, discontinuation of Doxepin should be strongly considered for patients who report a "sleep-driving" episode. Other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a hypnotic. As with "sleep-driving", patients usually do not remember these events. Amnesia, anxiety and other neuro-psychiatric symptoms may occur unpredictably.

Suicide Risk and Worsening of Depression: In primarily depressed patients, worsening of depression, including suicidal thoughts and actions (including completed suicides), has been reported in association with the use of hypnotics. Doxepin, the active ingredient in Doxepin, is an antidepressant at doses 10- to 100-fold higher than in Doxepin. Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Risk from the lower dose of doxepin in Doxepin can not be excluded. It can rarely be determined with certainty whether a particular instance of the abnormal behaviors listed above is drug induced, spontaneous in origin, or a result of an underlying psychiatric or physical disorder. Nonetheless, the emergence of any new behavioral sign or symptom of concern requires careful and immediate evaluation.

Pregnancy & Lactation

Pregnancy Category C. There are no adequate and well-controlled studies of Doxepin in pregnant women. Doxepin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Administration of doxepin to pregnant animals resulted in adverse effects on offspring development at doses greater than the maximum recommended human dose (MRHD) of 6 mg/day.

Doxepin is excreted in human milk after oral administration. There has been a report of apnea and drowsiness occurring in a nursing infant whose mother was taking the higher dose of doxepin used to treat depression. Caution should be exercised when Doxepin is administered to nursing women.