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{{Short description|Topical retinoid medication}}{{Use mdy dates|date=November 2022}}{{cs1 config|name-list-style=vanc|display-authors=6}}{{Drugbox| verifiedrevid = 470478004| image = Tazarotene.png| alt = Skeletal formula of tazarotene| width = 240| image2 = Tazarotene-3D-spacefill.png| alt2 = Space-filling model of the tazarotene molecule| tradename = Tazorac, others

monograph|tazarotene}}| pregnancy_category = | routes_of_administration = Topical| ATC_prefix = D05| ATC_suffix = AX05

D05|AX55}} (combination with ulobetasol)| legal_CA = Rx-only

HEALTH CANADA > DATE=3 AUGUST 2022

ACCESS-DATE=25 MARCH 2024, | legal_status = Rx-only| bioavailability = | protein_bound = >99%| metabolism = | elimination_half-life = 19 Hours

correct|??}}| CAS_number = 118292-40-3| PubChem = 5381| IUPHAR_ligand = 6952

correct|drugbank}}| DrugBank = DB00799

correct|chemspider}}| ChemSpiderID = 5188

correct|FDA}}| UNII = 81BDR9Y8PS

correct|kegg}}| KEGG = D01132

correct|EBI}}| ChEBI = 32184

correct|EBI}}| ChEMBL = 1657| IUPAC_name = ethyl 6-[2-(4,4-dimethyl-3,4-dihydro-2H-1-benzothiopyran-6-yl)ethynyl]pyridine-3-carboxylate| C = 21| H = 21| N = 1| O = 2| S = 1| smiles = O=C(OCC)c1ccc(nc1)C#Cc3ccc2SCCC(c2c3)(C)C

correct|chemspider}}| StdInChI = 1S/C21H21NO2S/c1-4-24-20(23)16-7-9-17(22-14-16)8-5-15-6-10-19-18(13-15)21(2,3)11-12-25-19/h6-7,9-10,13-14H,4,11-12H2,1-3H3

correct|chemspider}}| StdInChIKey = OGQICQVSFDPSEI-UHFFFAOYSA-N}}Tazarotene, sold under the brand name Tazorac, among others, is a third-generation prescription topical retinoid.JOURNAL, Thielitz A, Abdel-Naser MB, Fluhr JW, Zouboulis CC, Gollnick H, Topical retinoids in acne--an evidence-based overview, J Dtsch Dermatol Ges, 6, 12, 1023–31, December 2008, 18479477, 10.1111/j.1610-0387.2008.06741.x, free, WEB, American Society of Health-System Pharmacists, Inc., Tazarotene,medlineplus.gov/druginfo/meds/a616052.html, September 16, 2017, MedlinePlus Drug Information, U.S. National Library of Medicine, It is primarily used for the treatment of plaque psoriasis and acne.WEB, Tazarotene Monograph for Professionals,www.drugs.com/monograph/tazarotene.html, Drugs.com, American Society of Health-System Pharmacists, March 11, 2021, Tazarotene is also used as a therapeutic for photoaged and photodamaged skin. It is a member of the acetylenic class of retinoids.Tazarotene was approved for medical use in 1997WEB, Arazlo (tazarotene) [package insert],www.accessdata.fda.gov/drugsatfda_docs/label/2019/211882s000lbl.pdf, March 11, 2021, Drugs@FDA, U.S. Food and Drug Administration, and is available as a generic medication.WEB, 2022 First Generic Drug Approvals, U.S. Food and Drug Administration (FDA), 3 March 2023,www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/2022-first-generic-drug-approvals,web.archive.org/web/20230630003602/https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/2022-first-generic-drug-approvals, 30 June 2023, live, 30 June 2023, WEB, Competitive Generic Therapy Approvals, U.S. Food and Drug Administration (FDA), 29 June 2023,www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals, 29 June 2023, 29 June 2023,web.archive.org/web/20230629233651/https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals, live, Medical uses Tazarotene is most commonly used topically to treat acne vulgaris and psoriasis. Like other topical retinoids, such as tretinoin and adapalene, tazarotene can be combined with benzoyl peroxide or an oral antibiotic, such as clindamycin or dapsone, for the treatment of acne.JOURNAL, Kolli SS, Pecone D, Pona A, Cline A, Feldman SR, June 2019, Topical Retinoids in Acne Vulgaris: A Systematic Review, Am J Clin Dermatol, 20, 3, 345–365, 10.1007/s40257-019-00423-z, 30674002, 59225325, This results in increased efficacy compared to tazarotene monotherapy. For psoriasis, a combination therapy of tazarotene and a mid- to high-potency corticosteroid is more effective than either treatment alone.Tazarotene can also be used for the treatment of photodamaged skin. It can reduce the clinical and histological signs of photodamaged skin.JOURNAL, Stratigos AJ, Katsambas AD, 2005, The role of topical retinoids in the treatment of photoaging, Drugs, 65, 8, 1061–72, 10.2165/00003495-200565080-00003, 15907143, 24854629, The therapy is more effective when used with the daily application of sunscreen.JOURNAL, Ogden S, Samuel M, Griffiths CE, 2008, A review of tazarotene in the treatment of photodamaged skin, Clin Interv Aging, 3, 1, 71–6, 10.2147/cia.s1101, 2544371, 18488880, free, Pregnancy Before 2015, tazarotene was considered a Category X drug (meaning its use was contraindicated during pregnancy) according to Food and Drug Administration (FDA) guidelines, despite demonstrating similar plasma retinoid levels as adapalene and tretinoin, which were classified as Category C drugs.JOURNAL, Han G, Wu JJ, Del Rosso JQ, September 2020, Use of Topical Tazarotene for the Treatment of Acne Vulgaris in Pregnancy: A Literature Review, J Clin Aesthet Dermatol, 13, 9, E59–E65, 7577328, 33133344, Under the FDA’s updated Pregnancy and Lactation Labeling Rule which eliminated the lettered pregnancy categories and came into effect in 2015, tazarotene was determined to be contraindicated in pregnancy. Because of the lack of pregnancy outcomes data for the drug, the determination was based on the teratogenic effects observed in rat and rabbit studies. Contraindications Tazarotene is contraindicated for use in patients who are known to be or suspected of being pregnant. Tazarotene is a known teratogen. It is also contraindicated in patients with a known hypersensitivity to any ingredient in the specific pharmaceutical formulation. Adverse effects Adverse effects for tazarotene include skin irritation, such as redness, itchiness, and burning. In patients with psoriasis, these adverse effects can be mitigated by a combined treatment with either mometasone furoate or fluocinonide.JOURNAL, Foster RH, Brogden RN, Benfield P, Tazarotene, Drugs, 55, 5, 705–11; discussion 712, May 1998, 9585866, 10.2165/00003495-199855050-00008, 261765064, These effects tend to be mild to moderate, and increase in intensity as tazarotene concentration increases.JOURNAL, Mukherjee S, Date A, Patravale V, Korting HC, Roeder A, Weindl G, Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety, Clin Interv Aging, 1, 4, 327–48, 2006, 18046911, 2699641, 10.2147/ciia.2006.1.4.327, free, Pharmacology Mechanism of action Tazarotene is selective for two types of retinoic acid receptors, RAR-γ and RAR-β.JOURNAL, Duvic M, Nagpal S, Asano AT, Chandraratna RA, August 1997, Molecular mechanisms of tazarotene action in psoriasis, J Am Acad Dermatol, 37, 2 Pt 3, S18–24, 10.1016/S0190-9622(97)80396-9, 9270552, Like all retinoids, it affects the ability of keratinocytes in the epidermis to proliferate and differentiate. It does so by upregulating filaggrin expression and downregulating the expression of keratinocyte transglutaminase, ornithine decarboxylase, involucrin, epidermal growth factor receptor, and various keratins.JOURNAL, Heath MS, Sahni DR, Curry ZA, Feldman SR, September 2018, Pharmacokinetics of tazarotene and acitretin in psoriasis, Expert Opin Drug Metab Toxicol, 14, 9, 919–927, 10.1080/17425255.2018.1515198, 30134735, 52070149, Pharmacokinetics More than 99% of tazarotenic acid, the active metabolite of tazarotene, in the blood binds to plasma proteins (the most predominant being albumin).JOURNAL, Tang-Liu DD, Matsumoto RM, Usansky JI, October 1999, Clinical pharmacokinetics and drug metabolism of tazarotene: a novel topical treatment for acne and psoriasis, Clin Pharmacokinet, 37, 4, 273–87, 10.2165/00003088-199937040-00001, 10554045, 36445158, The volume of distribution (VD) for tazarotene is 26.1 L/kg and the VD for tazarotenic acid is 1.97 L/kg. Tazarotene is excreted from the body via feces and urine equally, and it has an elimination half-life of 16JOURNAL, Marks R, October 1998, Pharmacokinetics and safety review of tazarotene, J Am Acad Dermatol, 39, 4 Pt 2, S134–8, 10.1016/s0190-9622(98)70310-x, 9777791, to 18 hours.JOURNAL, Menter A, August 2000, Pharmacokinetics and safety of tazarotene, J Am Acad Dermatol, 43, 2 Pt 3, S31–5, 10.1067/mjd.2000.108321, 10898827, Synthesis Acetylenic retinoid prodrug converted to the active metabolite, tazarotenic acid, with selective affinity for retinoic acid receptors RARβ and RARγ. (File:Tazarotene synthesis.svg|thumb|center|700px|Tazarotene synthesis:Prepn: Chandraratna RA, PATENT, EP, 284288, ; idem, {{US patent|5089509}} (1988, 1992 both to Allergan).)The formation of the ring system involves first alkylation of the anion from thiophenol with dimethylallyl bromide (1) to give the thioether (2). Friedel-Crafts cyclization of the olefin with the equivalent of PPA then gives the thiopyran (3). Acylation with acetyl chloride in the presence of aluminium chloride gives the methyl ketone (4). Reaction of the enolate of that ketone with diethyl chlorophosphate gives the enol phosphate 5 as a transient intermediate. This eliminates diethyl phosphite in the presence of excess base to give the corresponding acetylene 6. The anion from the reaction of the acetylene with base is then used to displace chlorine from Ethyl 6-chloronicotinate (7). This reaction affords the coupling product tazarotene (8). References {{reflist}}{{Antipsoriatics}}{{Acne agents}}{{Carotenoids}}{{Retinoid receptor modulators}}