The drug is used commercially almost exclusively as the hydrochloride salt; the free base has been used rarely. The CAS Registry Number of the free base is 1668-19-5 and of the hydrochloride is 1229-29-4. History
Doxepin was discovered in Germany in 1963 and was introduced in the United States as an antidepressant in 1969. It was subsequently approved at very low doses in the United States for the treatment of insomnia in 2010. Society and culture
Generic names
Doxepin is the generic name of the drug in English and German and its INN and BAN, while doxepin hydrochloride is its USAN, USP, BANM, and JAN. Its generic name in Spanish and Italian and its DCIT are doxepina, in French and its DCF are doxépine, and in Latin is doxepinum.The cis or (Z) stereoisomer of doxepin is known as cidoxepin, and this is its INN while cidoxepin hydrochloride is its USAN. Brand names
It was introduced under the brand names Quitaxon and Aponal by Boehringer and as Sinequan by Pfizer.Doxepin is marketed under many brand names worldwide, including: Adnor, Anten, Antidoxe, Colian, Deptran, Dofu, Doneurin, Dospin, Doxal, Doxepini, Doxesom, Doxiderm, Flake, Gilex, Ichderm, Li Ke Ning, Mareen, Noctaderm, Oxpin, Patoderm, Prudoxin, Qualiquan, Quitaxon, Sagalon, Silenor, Sinepin, Sinequan, Sinquan, and Zonalon. It is also marketed as a combination drug with levomenthol under the brand name Doxure. Approvals
The oral formulations of doxepin are FDA-approved for the treatment of depression and sleep-maintenance insomnia, and its topical formulations are FDA-approved the short-term management for some itchy skin conditions.
Moreover, CYP2D6 poor metabolizers, as well as patients taking potent CYP2D6 inhibitors (which can potentially convert a CYP2D6 extensive metabolizer into a poor metabolizer), may be at an increased risk for adverse effects of doxepin due to their slower clearance of the drug.Another study assessed doxepin and nordoxepin metabolism in CYP2D6 ultra-rapid, extensive, and poor metabolizers following a single 75 mg oral dose. They found up to more than 10-fold variation in total exposure to doxepin and nordoxepin between the different groups. The researchers suggested that in order to achieve equivalent exposure, based on an average dose of 100%, the dosage of doxepin might be adjusted to 250% in ultra-rapid metabolizers, 150% in extensive metabolizers, 50% in intermediate metabolizers, and 30% in poor metabolizers. Chemistry
Doxepin is a tricyclic compound, specifically a dibenzoxepin, and possesses three rings fused together with a side chain attached in its chemical structure. It is the only TCA with a dibenzoxepin ring system to have been marketed. Doxepin is a tertiary amine TCA, with its side chain-demethylated metabolite nordoxepin being a secondary amine. Other tertiary amine TCAs include amitriptyline, imipramine, clomipramine, dosulepin (dothiepin), and trimipramine. Doxepin is a mixture of (E) and (Z) stereoisomers (the latter being known as cidoxepin or cis-doxepin) and is used commercially in a ratio of approximately 85:15. The chemical name of doxepin is (E/Z)-3-(dibenzo[b,e]oxepin-11(6H)-ylidene)-N,N-dimethylpropan-1-amine and its free base form has a chemical formula of C19H21NO with a molecular weight of 279.376 g/mol.