In short
Doxepin hydrochloride is a dibenzoxepin tricyclic compound used as an oral medicine for insomnia and under study as a topical cream. One authorised Phase 1 trial is assessing the bioequivalence of two doxepin hydrochloride creams in 24 healthy volunteers using dermal open flow microperfusion.
Key points
- Phase 1 trial authorised to assess bioequivalence of two topical doxepin hydrochloride creams.
- 24 healthy volunteers enrolled in a single-centre, randomised, controlled study.
- Uses dermal open flow microperfusion (dOFM) to measure drug levels in the skin.
- Study has no medical condition — it investigates cutaneous bioequivalence only.
- Doxepin is already authorised as an oral tablet for insomnia in the United States.
- The trial compares a test cream against a reference cream using dermal PK parameters such as AUC and Cmax.
What is doxepin hydrochloride?
Doxepin hydrochloride is a dibenzoxepin tricyclic compound. It is known by several names, including doxepin, doxepine, and the trade name Silenor. In the United States, doxepin tablets were first approved in 1969 and are indicated for the treatment of insomnia characterised by difficulties with sleep maintenance. The oral formulation is available as 3 mg and 6 mg film-coated tablets. Doxepin is also listed as a 10 mg oral capsule in the UK NHS dictionary of medicines. The substance is classified under ATC code N06AA12.
How does doxepin hydrochloride work?
Doxepin displays a range of pharmacological actions, including maintaining adrenergic innervation. Its exact mechanism of action is not fully understood. As a dibenzoxepin tricyclic compound, doxepin belongs to a class of medicines that act on the central nervous system.
Which conditions is it used or studied for?
- Insomnia — doxepin tablets are authorised in the United States for the treatment of insomnia characterised by difficulties with sleep maintenance.
- Topical bioequivalence — the registered clinical trial does not investigate a medical condition; it assesses the bioequivalence of two topical doxepin hydrochloride creams in healthy volunteers.
How is doxepin hydrochloride given?
Doxepin is available as an oral tablet and an oral capsule. The oral tablets are taken once daily within 30 minutes of bedtime. The registered clinical trial is studying a topical cream formulation of doxepin hydrochloride, applied to the skin.
What do the clinical trials show?
One clinical trial of doxepin hydrochloride is registered in the EU Clinical Trials Information System. It is a single-centre, randomised, controlled Phase 1 trial in 24 healthy volunteers. The trial has been authorised and no medical condition is being investigated. The study uses dermal open flow microperfusion (dOFM) to assess cutaneous bioequivalence between a test and a reference topical formulation of doxepin hydrochloride. The primary outcomes include dermal pharmacokinetic profiles, dermal PK parameters such as AUC(0 to 24)h, Cmax and tmax, and bioequivalence statistics such as geometric mean ratios, variability estimates and confidence limits. The trial involves two topical strengths: 550 mg and 400 mg.
What side effects are known?
The most common treatment-emergent adverse reactions reported in patients treated with oral doxepin, at a rate of 2% or more and more commonly than with placebo, were somnolence or sedation, nausea, and upper respiratory tract infection. Doxepin can impair alertness and motor coordination, and patients are advised to avoid hazardous activities such as operating a motor vehicle or heavy machinery after taking the drug. Abnormal thinking, behavioural changes and complex behaviours, including sleep-driving and hallucinations, may occur.