Important Safety Information — Doxepin

DRIFT Protocol

WARNING: SUICIDALITY AND ANTIDEPRESSANT DRUGS

Antidepressants, including doxepin, increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (ages 18-24) in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Although low-dose doxepin (3-6 mg) for insomnia is a lower dose than used for depression, the risk of suicidality cannot be excluded.

All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of therapy or at times of dose changes.

Indications

Low-dose doxepin (3-6 mg) is indicated for the treatment of insomnia characterized by difficulty with sleep maintenance. At these low doses, doxepin acts primarily as a selective histamine H1 receptor antagonist, promoting sleep without the significant anticholinergic and adrenergic effects seen at higher antidepressant doses.

Contraindications

Known hypersensitivity to doxepin hydrochloride or any component of the formulation
Untreated narrow-angle glaucoma
Severe urinary retention
Use within 14 days of stopping monoamine oxidase inhibitors (MAOIs), including linezolid or intravenous methylene blue, because of an increased risk of serotonin syndrome

Warnings and Precautions

Suicidality: Monitor all patients for worsening depression, suicidal thoughts, or unusual behavioral changes, particularly early in treatment or during dose adjustments.
CNS depressant effects: Doxepin can cause sleepiness and may affect the ability to make decisions, think clearly, or react quickly. Do not drive or operate heavy machinery until you know how doxepin affects you.
Elderly patients: Sleep-promoting drugs may cause over-sedation and confusion in older adults. A starting dose of 3 mg is recommended for patients 65 years and older.
Complex sleep behaviors: Sleep-walking, sleep-driving, and other activities while not fully awake may occur. Discontinue if complex behaviors develop.
Serotonin syndrome: Can occur when used with other serotonergic drugs or MAOIs. Symptoms include agitation, hallucinations, rapid heartbeat, fever, muscle stiffness, twitching, and incoordination. Seek immediate medical attention.
Hepatic impairment: Patients with liver impairment should be initiated at 3 mg and monitored closely for adverse daytime effects.
Alcohol: Do not consume alcohol during treatment. Alcohol can potentiate the sedative effects of doxepin.

Common Side Effects

Somnolence / drowsiness (next-day sedation)
Headache
Nausea
Upper respiratory tract infection
Dizziness
Dry mouth

Serious Side Effects

Seek medical attention immediately if you experience any of the following:

Worsening depression, suicidal thoughts, or unusual changes in behavior or mood
Signs of serotonin syndrome: agitation, hallucinations, rapid heartbeat, fever, muscle rigidity, loss of coordination, nausea, vomiting, diarrhea
Complex sleep behaviors (sleep-walking, sleep-driving, engaging in activities while not fully awake)
Severe allergic reaction: rash, hives, swelling of face, lips, tongue, or throat, difficulty breathing
Severe drowsiness, confusion, or inability to wake up
Irregular heartbeat
Seizures

Drug Interactions

MAO inhibitors: Contraindicated within 14 days of MAOI use due to risk of serotonin syndrome.
Cimetidine: Doubles doxepin exposure. When co-administered, the maximum doxepin dose should be 3 mg.
Alcohol: Potentiates sedative effects. Avoid alcohol during treatment.
Other CNS depressants: Use with caution when combined with antihistamines, anti-seizure drugs, sleep or anxiety medications, muscle relaxants, narcotics, or other psychiatric medicines.
Serotonergic drugs (e.g., SSRIs, SNRIs, triptans, tramadol): Risk of serotonin syndrome when used in combination.
Anticholinergic drugs: Additive anticholinergic effects (dry mouth, constipation, urinary retention, blurred vision).
Tolazamide: Severe hypoglycemia has been reported in a patient taking doxepin with tolazamide.

Use in Specific Populations

Pregnancy: There are no adequate and well-controlled studies in pregnant women. Use only if clearly needed.
Lactation: Doxepin and its active metabolite are excreted in human breast milk. Apnea and drowsiness have been reported in a nursing infant whose mother was taking doxepin. Exercise caution or discontinue nursing.
Pediatric use: Safety and effectiveness in pediatric patients have not been established. Not recommended for use in children.
Geriatric use: Start at 3 mg. Elderly patients are at greater risk for over-sedation and confusion.
Hepatic impairment: Start at 3 mg. Monitor closely for excessive sedation.