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Revision as of 18:45, 9 January 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,081 edits Saving copy of the {{drugbox}} taken from revid 457630615 of page Tazarotene for the Chem/Drugbox validation project (updated: 'DrugBank').		Latest revision as of 14:28, 21 January 2025 edit Ozzie10aaaa (talk | contribs)Autopatrolled, Extended confirmed users, New page reviewers214,299 edits Reference edited with ProveIt #proveitTag: ProveIt edit
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			{{Short description|Topical retinoid medication}}
	{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}}
			{{Use mdy dates|date=November 2022}}
			{{cs1 config|name-list-style=vanc|display-authors=6}}
	{{Drugbox		{{Drugbox
			| verifiedrevid = 470478004
	| Verifiedfields = changed
			| image = Tazarotene.png
	| verifiedrevid = 457629611
			| alt = Skeletal formula of tazarotene
	| IUPAC_name = ethyl 6-pyridine-3-carboxylate
			| width = 240
	| image = Tazarotene.png
			| image2 = Tazarotene-3D-spacefill.png
			| alt2 = Space-filling model of the tazarotene molecule
	<!--Clinical data-->		<!-- Clinical data -->
	| tradename = Tazorac		| tradename = Tazorac, others
	| Drugs.com = {{drugs.com|monograph|tazarotene}}		| Drugs.com = {{drugs.com|monograph|tazarotene}}
	| pregnancy_category = X <small>(])</small>		| pregnancy_category =
	| legal_status = Prescription Only
	| routes_of_administration = ]		| routes_of_administration = ]
			| ATC_prefix = D05
			| ATC_suffix = AX05
			| ATC_supplemental = <br />{{ATC|D05|AX55}} (combination with ])
	<!--Pharmacokinetic data-->		<!-- Legal status -->
			| legal_CA = Rx-only
	| bioavailability =
			| legal_CA_comment = /{{nbsp}}Schedule D<ref>{{Cite web |date=3 August 2022 |title=Health product highlights 2021: Annexes of products approved in 2021 |url=https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/health-product-highlights-2021/appendices.html |access-date=25 March 2024 |website=]}}</ref>
	| protein_bound = >99%
			| legal_status = Rx-only
	| metabolism =
			<!-- Pharmacokinetic data -->
			| bioavailability =
			| protein_bound = >99%
			| metabolism =
	| elimination_half-life = 19 Hours		| elimination_half-life = 19 Hours
	<!--Identifiers-->		<!-- Identifiers -->
	| CASNo_Ref = {{cascite|correct|CAS}}		| CAS_number_Ref = {{cascite|correct|??}}
			| CAS_number = 118292-40-3
	| CAS_number_Ref = {{cascite|correct|??}}
			| PubChem = 5381
	| CAS_number = 118292-40-3
			| IUPHAR_ligand = 6952
	| ATC_prefix = D05
			| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
	| ATC_suffix = AX05
			| DrugBank = DB00799
	| ATC_supplemental =
			| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
	| PubChem = 5381
			| ChemSpiderID = 5188
	| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
			| UNII_Ref = {{fdacite|correct|FDA}}
	| DrugBank = DB00799
			| UNII = 81BDR9Y8PS
	| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
			| KEGG_Ref = {{keggcite|correct|kegg}}
	| ChemSpiderID = 5188
			| KEGG = D01132
	| UNII_Ref = {{fdacite|correct|FDA}}
			| ChEBI_Ref = {{ebicite|correct|EBI}}
	| UNII = 81BDR9Y8PS
			| ChEBI = 32184
	| KEGG_Ref = {{keggcite|correct|kegg}}
			| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| KEGG = D01132
			| ChEMBL = 1657
	| ChEBI_Ref = {{ebicite|correct|EBI}}
	| ChEBI = 32184
	| ChEMBL_Ref = {{ebicite|correct|EBI}}
	| ChEMBL = 1657
	<!--Chemical data-->		<!-- Chemical data -->
			| IUPAC_name = ethyl 6-pyridine-3-carboxylate
	| C=21 | H=21 | N=1 | O=2 | S=1
			| C = 21
	| molecular_weight = 351.463 g/mol
			| H = 21
	| smiles = O=C(OCC)c1ccc(nc1)C#Cc3ccc2SCCC(c2c3)(C)C
			| N = 1
	| InChI = 1/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
			| O = 2
	| InChIKey = OGQICQVSFDPSEI-UHFFFAOYAD
			| S = 1
	| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
			| smiles = O=C(OCC)c1ccc(nc1)C#Cc3ccc2SCCC(c2c3)(C)C
	| 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
	| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}		| StdInChI_Ref = {{stdinchicite|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
	| StdInChIKey = OGQICQVSFDPSEI-UHFFFAOYSA-N
			| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
			| StdInChIKey = OGQICQVSFDPSEI-UHFFFAOYSA-N
	}}		}}
			'''Tazarotene''', sold under the brand name '''Tazorac''', among others, is a third-generation ] topical ].<ref name="Thielitz2008">{{Cite journal |vauthors=Thielitz A, Abdel-Naser MB, Fluhr JW, Zouboulis CC, Gollnick H |date=December 2008 |title=Topical retinoids in acne--an evidence-based overview |journal=J Dtsch Dermatol Ges |volume=6 |issue=12 |pages=1023–31 |doi=10.1111/j.1610-0387.2008.06741.x |pmid=18479477 |doi-access=free}}</ref><ref name="medline">{{Cite web |last=American Society of Health-System Pharmacists, Inc. |title=Tazarotene |url=https://medlineplus.gov/druginfo/meds/a616052.html |access-date=September 16, 2017 |website=MedlinePlus Drug Information |publisher=U.S. National Library of Medicine}}</ref> It is primarily used for the treatment of ] and ].<ref name="drugs">{{Cite web |title=Tazarotene Monograph for Professionals |url=https://www.drugs.com/monograph/tazarotene.html |access-date=March 11, 2021 |website=Drugs.com |publisher=American Society of Health-System Pharmacists}}</ref> Tazarotene is also used as a therapeutic for ] and photodamaged skin.<ref name="drugs" /> It is a member of the acetylenic class of retinoids.<ref name="drugs" />
			Tazarotene was approved for medical use in 1997<ref name="Arazlo">{{Cite web |title=Arazlo (tazarotene) |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211882s000lbl.pdf |access-date=March 11, 2021 |website=Drugs@FDA |publisher=U.S. Food and Drug Administration}}</ref> and is available as a ].<ref>{{Cite web |date=3 March 2023 |title=2022 First Generic Drug Approvals |url=https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/2022-first-generic-drug-approvals |url-status=live |archive-url=https://web.archive.org/web/20230630003602/https://www.fda.gov/drugs/drug-and-biologic-approval-and-ind-activity-reports/2022-first-generic-drug-approvals |archive-date=30 June 2023 |access-date=30 June 2023 |website=U.S. ] (FDA)}}</ref><ref>{{Cite web |date=29 June 2023 |title=Competitive Generic Therapy Approvals |url=https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals |url-status=live |archive-url=https://web.archive.org/web/20230629233651/https://www.fda.gov/drugs/generic-drugs/competitive-generic-therapy-approvals |archive-date=29 June 2023 |access-date=29 June 2023 |website=U.S. ] (FDA)}}</ref>
			==Medical uses==
			Tazarotene is most commonly used topically to treat ] and ].<ref name="drugs" /> Like other topical ], such as ] and ], tazarotene can be combined with ] or an oral antibiotic, such as ] or ], for the treatment of acne.<ref name="kolli2019">{{Cite journal |vauthors=Kolli SS, Pecone D, Pona A, Cline A, Feldman SR |date=June 2019 |title=Topical Retinoids in Acne Vulgaris: A Systematic Review |journal=Am J Clin Dermatol |volume=20 |issue=3 |pages=345–365 |doi=10.1007/s40257-019-00423-z |pmid=30674002 |s2cid=59225325}}</ref> This results in increased efficacy compared to tazarotene ].<ref name="kolli2019" /> For psoriasis, a combination therapy of tazarotene and a mid- to high-potency ] is more effective than either treatment alone.<ref name="foster1998" />
			Tazarotene can also be used for the treatment of photodamaged skin. It can reduce the clinical and ] signs of photodamaged skin.<ref name="stratigos2005">{{Cite journal |vauthors=Stratigos AJ, Katsambas AD |date=2005 |title=The role of topical retinoids in the treatment of photoaging |journal=Drugs |volume=65 |issue=8 |pages=1061–72 |doi=10.2165/00003495-200565080-00003 |pmid=15907143 |s2cid=24854629}}</ref> The therapy is more effective when used with the daily application of ].<ref name="ogden2008">{{Cite journal |vauthors=Ogden S, Samuel M, Griffiths CE |date=2008 |title=A review of tazarotene in the treatment of photodamaged skin |journal=Clin Interv Aging |volume=3 |issue=1 |pages=71–6 |doi=10.2147/cia.s1101 |pmc=2544371 |pmid=18488880 |doi-access=free}}</ref>
			===Pregnancy===
			Before 2015, tazarotene was considered a Category X drug (meaning its use was contraindicated during pregnancy) according to ] (FDA) guidelines, despite demonstrating similar plasma retinoid levels as adapalene and tretinoin, which were classified as Category C drugs.<ref name="han2020">{{Cite journal |vauthors=Han G, Wu JJ, Del Rosso JQ |date=September 2020 |title=Use of Topical Tazarotene for the Treatment of Acne Vulgaris in Pregnancy: A Literature Review |journal=J Clin Aesthet Dermatol |volume=13 |issue=9 |pages=E59–E65 |pmc=7577328 |pmid=33133344}}</ref> 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.<ref name="han2020" /> 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.<ref name="Arazlo" /><ref name="han2020" />
			==Contraindications==
			Tazarotene is contraindicated for use in patients who are known to be or suspected of being pregnant. Tazarotene is a known teratogen.<ref name="drugs" />
			==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 ] or ].<ref name="foster1998">{{Cite journal |vauthors=Foster RH, Brogden RN, Benfield P |date=May 1998 |title=Tazarotene |journal=Drugs |volume=55 |issue=5 |pages=705–11; discussion 712 |doi=10.2165/00003495-199855050-00008 |pmid=9585866 |s2cid=261765064}}</ref> These effects tend to be mild to moderate, and increase in intensity as tazarotene concentration increases.<ref name="mukherjee2006">{{Cite journal |vauthors=Mukherjee S, Date A, Patravale V, Korting HC, Roeder A, Weindl G |date=2006 |title=Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety |journal=Clin Interv Aging |volume=1 |issue=4 |pages=327–48 |doi=10.2147/ciia.2006.1.4.327 |pmc=2699641 |pmid=18046911 |doi-access=free}}</ref>
			== Pharmacology ==
			=== Mechanism of action ===
			Tazarotene is selective for two types of retinoic acid receptors, ] and ].<ref name="duvic1997">{{Cite journal |vauthors=Duvic M, Nagpal S, Asano AT, Chandraratna RA |date=August 1997 |title=Molecular mechanisms of tazarotene action in psoriasis |journal=J Am Acad Dermatol |volume=37 |issue=2 Pt 3 |pages=S18–24 |doi=10.1016/S0190-9622(97)80396-9 |pmid=9270552}}</ref> Like all retinoids, it affects the ability of ]s in the ] to ] and ].<ref name="duvic1997" /> It does so by upregulating ] expression and downregulating the expression of ], ], ], ], and various ].<ref name="heath2018">{{Cite journal |vauthors=Heath MS, Sahni DR, Curry ZA, Feldman SR |date=September 2018 |title=Pharmacokinetics of tazarotene and acitretin in psoriasis |journal=Expert Opin Drug Metab Toxicol |volume=14 |issue=9 |pages=919–927 |doi=10.1080/17425255.2018.1515198 |pmid=30134735 |s2cid=52070149}}</ref>
			=== Pharmacokinetics ===
			More than 99% of tazarotenic acid, the active metabolite of tazarotene, in the blood binds to plasma proteins (the most predominant being ]).<ref name="tang1999">{{Cite journal |vauthors=Tang-Liu DD, Matsumoto RM, Usansky JI |date=October 1999 |title=Clinical pharmacokinetics and drug metabolism of tazarotene: a novel topical treatment for acne and psoriasis |journal=Clin Pharmacokinet |volume=37 |issue=4 |pages=273–87 |doi=10.2165/00003088-199937040-00001 |pmid=10554045 |s2cid=36445158}}</ref> The ] (V<sub>D</sub>) for tazarotene is 26.1 L/kg and the V<sub>D</sub> for tazarotenic acid is 1.97 L/kg.<ref name="tang1999" /> Tazarotene is excreted from the body via feces and urine equally,<ref name="foster1998" /> and it has an elimination half-life of 16<ref name="marks1998">{{Cite journal |vauthors=Marks R |date=October 1998 |title=Pharmacokinetics and safety review of tazarotene |journal=J Am Acad Dermatol |volume=39 |issue=4 Pt 2 |pages=S134–8 |doi=10.1016/s0190-9622(98)70310-x |pmid=9777791}}</ref> to 18 hours.<ref name="menter2000">{{Cite journal |vauthors=Menter A |date=August 2000 |title=Pharmacokinetics and safety of tazarotene |journal=J Am Acad Dermatol |volume=43 |issue=2 Pt 3 |pages=S31–5 |doi=10.1067/mjd.2000.108321 |pmid=10898827}}</ref>
			==Synthesis==
			Acetylenic retinoid prodrug converted to the active metabolite, ], with selective affinity for retinoic acid receptors RARβ and RARγ.
			]
			The formation of the ring system involves first alkylation of the anion from ] 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 ] in the presence of ] gives the methyl ketone ('''4'''). Reaction of the enolate of that ketone with ] gives the enol phosphate '''5''' as a transient intermediate. This eliminates ] 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}}
			]
			]
			]
			]
			]
			]
			]
			]
			]