Monographs of Topical Drugs that Have Caused Contact Allergy/Allergic Contact Dermatitis
Anton C. de Groot in Monographs in Contact Allergy, 2021
Doxepin is a dibenzoxepin derivative and tricyclic antidepressant-like drug with antipruritic, anti-depressive, sedative and anxiolytic activities with structural similarities to phenotheazines. Oral doxepin is approved for treatment of depression and/or anxiety associated with different conditions, including alcoholism, organic disease and manic-depressive disorders and for treatment of insomnia characterized by difficulties with sleep maintenance. Topical doxepin is also approved for short-term (up to 8 days) management of moderate pruritus in adult patients with atopic dermatitis, pruritus or lichen simplex chronicus. In pharmaceutical products, doxepin is employed as doxepin hydrochloride (CAS number 1229-29-4, EC number 214-966-8, molecular formula C19H22ClNO) (1).
Substrates of Human CYP2D6
Shufeng Zhou in Cytochrome P450 2D6, 2018
Doxepin is a tricyclic antidepressant that inhibits the reup-take of serotonin and noradrenaline from the synaptic cleft (Pinder et al. 1977a). Doxepin is given as a 15:85 mixture of Z-cis-IE-trans-isomers, with Z-cis-doxepin being considered to have greater antidepressive effect. Doxepin is extensively metabolized in the liver, and its Phase I and Phase II metabolites have been identified in human plasma, urine, and cerebrospinal fluid (Shu et al. 1990). The urinary metabolites in humans are (E)-2-hydroxydoxepin, (E)-2-hydroxy-N-desmethyldoxepin, (Z)- and (E)-N-desmethyldoxepin, (Z)- and (E)-doxepin-N-oxide, (E)-2-O-glucuronyldoxepin, and a quaternary ammonium-linked glucuronide (Shu et al. 1990). The N+-glucuronide is a major metabolite in patient urine after doxepin administration. CYP2D6 mainly converts the E-isomer of doxepin to its active metabolite 2-hydroxy derivative while the formation of N-desmethyldoxepin is mainly catalyzed by CYP2C19 and 3A4 (Figure 3.6) (Haritos et al. 2000; Hartter et al. 2002; Kirchheiner et al. 2002).
Anxiolytics: Predicting Response/Maximizing Efficacy
Mark S. Gold, R. Bruce Lydiard, John S. Carman in Advances in Psychopharmacology: Predicting and Improving Treatment Response, 2018
Obsessive-compulsive disorder is very difficult to treat and it is often unresponsive to psychotherapy, neuroleptics, ECT, and psychosurgery.293 However, the efficacy of the tricyclic drugs to reduce anxiety in such cases can be clearly seen from the Western experience with clomipramine. A series of uncontrolled trials revealed clomipramine to be an effective drug in obsessive-compulsive disorder.294–296 Controlled double-blind studies have confirmed the efficacy of clomipramine in obsessive-compulsive disorder.216,297,298 A pharmacologically similar drug, doxepin, has been shown in an uncontrolled trial to be effective also.299 Notriptyline also has been shown in double-blind study to be superior to placebo in the treatment of obsessive-compulsive disorder symptoms.300 Thus, drugs of the tricyclic class are in general effective upon anxiety and obsessive-compulsive rituals in obsessive-compulsive disorder. Anxiety and rituals decline in parallel from 21 to 42%.300
Current and emerging pharmacotherapy for chronic spontaneous Urticaria: a focus on non-biological therapeutics
Published in Expert Opinion on Pharmacotherapy, 2021
Kam Lun Hon, Joyce T. S. Li, Alexander K.C. Leung, Vivian W. Y. Lee
Doxepin is a tricyclic antidepressant which has potent H1 and H2 receptor antagonist activity. Maximum response could usually be achieved within a few days. Doxepin has been proven to be equal or superior to antihistamines mequitazine and diphenhydramine in the treatment of CU [82,83]. A randomized double-blinded cross-over study on 50 CSU patients compared doxepin (10 mg, 3 times a day) to diphenhydramine (25 mg, 3 times a day) [82]. Total clearance of itching and urticarial lesions was seen in 43% of patients receiving doxepin versus 5% of patients who received diphenhydramine (p < 0.001). Partial or total control of itching and hives was reported in 74% of patients receiving doxepin versus 10% of patients who received diphenhydramine (p < 0.001). In addition, doxepin induced less sedation than diphenhydramine [82]. Mirtazapine, a piperazinoazepine tetracyclic antidepressant, may also be efficacious in CSU. A case report described a patient who entered remission from severe CU after seven days of mirtazapine use [84]. The patient experienced relapse within one week of discontinuation, but reintroducing mirtazapine yielded good response [84]. Two patients with concurrent CU and panic disorder who previously required systemic corticosteroids showed symptom improvement after starting sertraline and fluoxetine [85]. Responses lasted throughout the treatment periods.
Drug treatment strategies for insomnia in patients with post-traumatic stress disorder
Published in Expert Opinion on Pharmacotherapy, 2019
Morohunfolu Akinnusi, Ali A. El Solh
Doxepin (Silenor) is a tricyclic antidepressant that gained FDA approval for the treatment of insomnia in 2010. Doxepin is the most potent antihistamine of the tricyclic antidepressants, with four times the potency of amitriptyline and 800 times the potency of diphenhydramine at the H1 receptor [50]. A dose-response effect is usually observed within 1–6 mg doxepin. At these lower doses, doxepin has shown the efficacy of sleep maintenance insomnia attributed to its histaminic H1 receptor antagonist [51]. Existing evidence suggests that low dose doxepin is effective at reducing symptoms of primary insomnia [52]. However, there have been no studies evaluating its effectiveness in PTSD patients with insomnia. The advantage of Doxepin resides in the fact that it is devoid of abuse, tolerance, or withdrawal complications. Somnolence is the most commonly reported adverse event followed by headache, dry mouth, and dizziness [52]. Doxepin is contraindicated in patients with glaucoma or severe urinary retention. Other tricyclic antidepressants such as imipramine and amitriptyline have been prescribed for the treatment of insomnia in PTSD, but concerns about cardiac toxicity and anticholinergic activity have limited their utility.
Optimizing doxepin therapy in dermatology: introducing blood level monitoring and genotype testing
Published in Journal of Dermatological Treatment, 2022
Bridget Myers, Vidhatha Reddy, Stephanie Chan, Quinn Thibodeaux, Nicholas Brownstone, John Koo
Doxepin is an especially efficacious antipruritic agent in dermatology, but due to interindividual variability in clinical response the typical dermatologic dosing range may prove subtherapeutic in many patients. For this reason, both a 300 mg per day maximum dose and a 10 mg per cc liquid doxepin concentrate have been approved by the FDA. It is important for the practicing dermatologist to understand that a variety of factors are capable of affecting doxepin pharmacokinetics, so that patients initially unresponsive or intolerant to treatment are first considered cases of needed dosage adjustment and not treatment failures. BLM is an efficacious, widely available tool that can help dermatologists make safe dose adjustments to reach therapeutic concentrations.
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