Brand names: Prudoxin, Zonalon
Drug class: Antipruritics and Local Anesthetics

Medically reviewed by Drugs.com on Apr 10, 2024. Written by ASHP.

Introduction

Antipruritic agent; dibenzoxepin-derivative tricyclic antidepressant compound with antihistaminic activity.^{1 2 4 5 6 b c}

Uses for Doxepin (Topical)

Dermatologic Conditions

Used for short-term (up to 8 days) relief of moderate pruritus associated with various forms of eczematous dermatitis, including atopic dermatitis and lichen simplex chronicus (circumscribed or localized neurodermatitis).^{1 2 b c}

Doxepin (Topical) Dosage and Administration

Administration

Topical Administration

Apply topically to the skin as a 5% cream.^{1 2 b c}

For external use only;^{1 c} should not be used near or in eyes, orally, or intravaginally.^{1 b c}

Do not use with occlusive dressings (e.g., bandaged or otherwise covered or wrapped).^{3 b c} (See Occlusive Dressings under Cautions.)

Dosage

Available as doxepin hydrochloride; dosage expressed in terms of the salt.^{b c}

Adults

Dermatologic Conditions

Topical

Apply a thin film to affected area(s) of the skin 4 times daily, with an interval of at least 3–4 hours between applications, for up to 8 days.^{1 b c d}

Prescribing Limits

Adults

Dermatologic Conditions

Topical

Safety and efficacy of >8 days of therapy not established.^{1 b c}

Special Populations

Geriatric Patients

Select dosage with caution, generally start at low end of dosing range, due to possible age-related decrease in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.^b

Cautions for Doxepin (Topical)

Contraindications

• Untreated narrow angle glaucoma.^{b d}

• Urinary retention.^{b d}

• Known sensitivity to doxepin or any ingredient in the formulation.^{b d}

Warnings/Precautions

Warnings

CNS Effects

Drowsiness reported in >20% of patients following topical application, especially when applied to >10% of body surface area.^{1 b c d}

Performance of activities requiring mental alertness and physical coordination may be impaired.^{b c}

Concurrent use of other CNS depressants may cause additive or potentiated CNS depression.^{b c} (See Specific Drugs under Interactions.)

If excessive drowsiness occurs, reduce number of daily applications, the amount of cream applied, and/or the percentage of body surface area treated, or discontinue the drug.^{1 b c} Efficacy of cream with reduced frequency applications not established.^b

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions, including allergic contact dermatitis reported.^{b c}

General Precautions

Occlusive Dressings

Possible increased absorption; avoid occlusive dressings.^{b c}

Specific Populations

Pregnancy

Category B.^{b c}

Lactation

Not known whether topical doxepin is distributed into milk, but systemic exposure may occur after topical administration.^{b c} Distributed into milk following oral administration.^{b c} Discontinue nursing or the drug.^{b c}

Pediatric Use

Safety and efficacy of topical doxepin not established.^{1 b c} Manufacturer does not recommend topical doxepin in pediatric patients.^b

Somnolence, grand mal seizure, respiratory depression, ECG abnormalities, and coma reported in a 2.5 year old pediatric patient following topical doxepin administration (27 grams) over 3 days.^b

Geriatric Use

Clinical studies did not include sufficient numbers of subjects ≥65 years of age to determine whether they respond differently from younger subjects.^b

May cause confusion and oversedation in geriatric patients;^b observe geriatric patients closely following doxepin cream administration.^b

Common Adverse Effects

Drowsiness,^{b c} burning,^d dry mouth,^{b c} dry lips,^{b c} thirst.^{b c}

Drug Interactions

No interactions identified to date when topical doxepin used concomitantly with other topical or systemic drugs.^{b c} Because clinically relevant systemic absorption may occur following topical application, drug interactions between topical doxepin and systemically administered drugs may occur.^{b c} (See Absorption under Pharmacokinetics.)

Metabolized in the liver by various CYP isoenzymes (e.g., CYP2D6, CYP1A2, CYP3A4).^e

Drugs Metabolized by Hepatic Microsomal Enzymes

Inhibitors and substrates of CYP2D6; potential pharmacokinetic interaction (increased plasma doxepin concentrations). Consider possible interactions related to TCA class of drugs.^{b c}

Specific Drugs

Doxepin (Topical) Pharmacokinetics

Absorption

Bioavailability

Absorbed percutaneously into systemic circulation following topical application.^{1 b c} Plasma concentrations following topical application may be similar to those occurring following oral administration.^{b d}

Percutaneous penetration can be increased by use of occlusive dressings.^{b c}

Onset

Following topical application, antipruritic effects may occur within 15 minutes.^d

Distribution

Extent

Widely distributed in body tissues including lungs, heart, brain, and liver.^b

Not known whether topical doxepin is distributed into milk; distributed into milk following oral administration.^{b c}

Elimination

Metabolism

Extensively metabolized in the liver by various CYP isoenzymes (principally CYP2D6); undergoes demethylation to pharmacologically active metabolite, desmethyldoxepin.^{b e}

Elimination Route

Excreted in urine following glucuronidation as unchanged drug and metabolites.^b

Half-life

Half-life of desmethyldoxepin ranges from 28 to 52 hours and is not affected by multiple dosing.^b

Special Populations

Renal disease, genetic factors, age, and other medications may affect the metabolism and subsequent elimination of doxepin.^b

Stability

Storage

Topical

Cream

≤27°C.^{b c}

Actions

• Exact mechanism of antipruritic activity is unknown; appears to exhibit potent histamine H₁- and H₂-receptor antagonist activity.^{1 2 4 5 6 b d}

• Sedative effect may contribute to antipruritic activity;^{1 b} however, antipruritic efficacy does not appear to depend on sedative effect.^{2 3}

Advice to Patients

• Importance of using only as directed, only for the disorder for which it was prescribed, and for no longer than prescribed; avoid contact with the eyes and only apply externally as directed.^{c d}

• Importance of avoiding use of occlusive dressings.^{3 b c}

• Risk of drowsiness, especially if doxepin cream is applied to >10% of body surface area.^{1 b c d}

• Importance of considering possible impaired ability to perform hazardous activities (e.g., operating hazardous machinery, driving a motor vehicle).^{b c}

• Inform patients that their response to alcohol may be increased.^{b c}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{b c}

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.^d

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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