What is the recommended dose of doxepin (tricyclic antidepressant) for treating pruritus?

Doxepin Dosing for Pruritus

For uremic pruritus in hemodialysis patients, use doxepin 10 mg orally twice daily, while topical doxepin 5% cream should be limited to 8 days maximum, applied to no more than 10% body surface area, with a daily maximum of 12 grams for generalized pruritus of unknown origin. 1

Oral Doxepin Dosing

Uremic Pruritus (Hemodialysis Patients)

• Dose: 10 mg orally twice daily 1, 2
• This regimen achieved complete resolution of pruritus in 58% of patients versus 8% with placebo, with an overall improvement rate of 87.5% 1, 2
• Common side effect: Drowsiness occurs in 50% of patients but typically resolves within 2 days and is well-tolerated 1, 2
• One important caveat: approximately 4% of patients may discontinue due to excessive sedation 1, 2

Generalized Pruritus of Unknown Origin (GPUO)

• Oral doxepin can be considered as a second-line systemic agent when antihistamines fail 1, 3
• No specific oral dose is established in guidelines for GPUO, but extrapolating from uremic pruritus data suggests 10 mg twice daily as a reasonable starting point 1, 2

Topical Doxepin Dosing

For Atopic Dermatitis and Localized Pruritus

• Concentration: 5% doxepin hydrochloride cream 4, 5
• Frequency: Apply 4 times daily 4, 5
• Achieves pruritus relief in 85% of patients with atopic dermatitis versus 57% with vehicle, with majority of responses occurring within the first 24 hours 5

Critical Safety Limitations for Topical Use

The British Association of Dermatologists provides strict restrictions for topical doxepin due to toxicity and sensitization risks: 1, 3

• Maximum duration: 8 days only 1, 3
• Maximum body surface area: 10% 1, 3
• Maximum daily amount: 12 grams 1, 3

Important Warnings for Topical Doxepin

• Contraindicated in children under 12 years: A case report documented severe altered mental status in a 5-year-old after application of 30 grams over 24 hours, requiring pediatric ICU admission 6
• Risk of allergic contact dermatitis necessitates the short treatment duration 1
• Systemic absorption occurs, particularly with compromised skin integrity or large application areas 4, 6

Clinical Context by Pruritus Type

When to Use Doxepin

Doxepin functions as both a tricyclic antidepressant and potent H1/H2 histamine antagonist, making it useful for antihistamine-resistant pruritus 1, 3

Position in treatment algorithm:

• First-line for uremic pruritus: 10 mg twice daily after other measures (adequate dialysis, emollients) 1
• Second-line for GPUO: Consider after failure of non-sedating antihistamines 1, 3
• Alternative for cancer therapy-related pruritus: When standard antihistamines are insufficient 1

Important Contraindications

• Long-term use should be avoided except in palliative settings due to concerns about dementia risk with chronic sedating antihistamines 1, 7
• Avoid in severe liver disease due to inappropriate sedation 7
• Contraindicated in early pregnancy 7
• Use with caution in elderly patients with cognitive impairment due to anticholinergic effects 7

Practical Prescribing Approach

For oral doxepin in uremic pruritus:

• Start 10 mg twice daily 1, 2
• Warn patients about drowsiness, which typically improves after 2 days 1, 2
• Expect response within the first week of treatment 1, 2

For topical doxepin:

• Use only 5% cream formulation 4, 5
• Apply 4 times daily to affected areas 4, 5
• Never exceed 8 days, 10% body surface area, or 12 grams daily 1, 3
• Monitor for local burning/stinging (common but decreases over time) and systemic drowsiness 5