Doxepin is indicated for the treatment of insomnia characterized by difficulty with sleep maintenance (trouble staying asleep). The clinical trials supporting its efficacy were conducted for up to 3 months in duration.

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 it is believed to be due to its antagonism of the H₁ receptor.

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.

Cytochrome P450 Isozymes: Doxepin is mainly metabolized by liver enzymes CYP2C19 and CYP2D6, with minor involvement of CYP1A2 and CYP2C9. Inhibitors of these enzymes may increase doxepin levels. Doxepin does not significantly inhibit CYP enzymes at therapeutic doses, and its enzyme-inducing potential remains unclear.

Cimetidine: Concurrent use with cimetidine, a non-specific CYP inhibitor, can significantly increase doxepin levels. A lower maximum dose (3 mg) is advised in adults and elderly patients when used together.

Alcohol: Alcohol may enhance the sedative effects of doxepin.

CNS Depressants and Sedating Antihistamines: Combined use may increase sedation and CNS depressant effects.

Tolazamide: Severe hypoglycemia has been reported in diabetic patients when tolazamide is used alongside doxepin.

Hypersensitivity: Contraindicated in patients with known allergy to doxepin or related compounds.

Use with MAO Inhibitors: Concurrent or recent use (within 2 weeks) with MAO inhibitors is contraindicated due to risk of severe adverse effects or death.

Glaucoma and Urinary Retention: Contraindicated in patients with untreated narrow-angle glaucoma or severe urinary retention.

Serious adverse effects may include abnormal thinking and behavioral changes, increased risk of suicide or worsening depression, and central nervous system depression.

Doxepin belongs to Pregnancy Category C. It should be used during pregnancy only if the expected benefit outweighs potential risk. Animal studies have shown adverse developmental effects at high doses.

Doxepin is excreted in breast milk. Reports of drowsiness and apnea in infants exist; therefore, caution is advised when used in breastfeeding mothers.

Evaluation for underlying disorders: Insomnia may be a symptom of other medical or psychiatric conditions; proper evaluation is necessary before treatment.

Behavioral changes: Complex behaviors such as sleep-driving and other activities may occur, especially with alcohol or CNS depressants. Discontinuation is advised if such events occur.

Suicide risk and worsening depression: Patients with depression may experience worsening symptoms or suicidal thoughts. Close monitoring is required, especially in younger individuals.

Tricyclic & related anti-depressant drugs

Store below 30°C in a cool, dry place, protected from light. Keep out of reach of children.