trifarotene
{{Short description|Chemical compound}}
{{Use American English|date=May 2021}}
{{Use dmy dates|date=July 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| image = Trifarotene.svg
| width =
| alt =
| caption =
| pronounce =
| tradename = Aklief, Selgamis
| Drugs.com = {{drugs.com|monograph|trifarotene}}
| MedlinePlus = a620004
| DailyMedID = Trifarotene
| pregnancy_AU = D
| pregnancy_category= Contraindicated
| routes_of_administration = Topical
| class = Skin and mucous membrane agents
| ATC_prefix = D10
| ATC_suffix = AD06
| ATC_supplemental =
| legal_AU = S4
| legal_AU_comment = {{Cite web |title=Trifarotene Product Information |url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2021-PI-01076-1 |url-status=live |archive-url=https://web.archive.org/web/20210523190514/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2021-PI-01076-1 |archive-date=23 May 2021 |access-date=23 May 2021 |website=Therapeutic Goods Administration (TGA)}}{{Cite web |date=28 January 2021 |title=Aklief |url=https://www.tga.gov.au/apm-summary/aklief |url-status=live |archive-url=https://web.archive.org/web/20210909014105/https://www.tga.gov.au/apm-summary/aklief |archive-date=9 September 2021 |access-date=8 September 2021 |website=Therapeutic Goods Administration (TGA)}}
| legal_BR =
| legal_BR_comment =
| legal_CA = Rx-only
| legal_CA_comment = {{Cite web |title=PRODUCT MONOGRAPH Trifarotene cream |url=https://pdf.hres.ca/dpd_pm/00054047.PDF |url-status=live |archive-url=https://web.archive.org/web/20210523220540/https://pdf.hres.ca/dpd_pm/00054047.PDF |archive-date=23 May 2021 |access-date=23 May 2021}}{{Cite web |date=23 October 2014 |title=Summary Basis of Decision (SBD) for Aklief |url=https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00464&lang=en |url-status=live |archive-url=https://web.archive.org/web/20220531043601/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00464&lang=en |archive-date=31 May 2022 |access-date=29 May 2022 |website=Health Canada}}
| legal_DE =
| legal_DE_comment =
| legal_NZ =
| legal_NZ_comment =
| legal_UK = POM
| legal_US = Rx-only
| legal_EU =
| legal_EU_comment =
| legal_UN =
| legal_UN_comment =
| bioavailability =
| protein_bound =
| metabolism =
| metabolites =
| onset =
| elimination_half-life =
| duration_of_action =
| excretion =
| CAS_number = 895542-09-3
| CAS_supplemental =
| PubChem = 11518241
| PubChemSubstance =
| IUPHAR_ligand =
| DrugBank = DB12808
| ChemSpiderID = 9693029
| UNII = 0J8RN2W0HK
| KEGG = D11225
| ChEBI =
| ChEMBL = 3707313
| NIAID_ChemDB =
| PDB_ligand =
| synonyms = CD5789
| IUPAC_name = 4-[3-(3-tert-Butyl-4-pyrrolidin-1-ylphenyl)-4-(2-hydroxyethoxy)phenyl]benzoic acid
| C=29 | H=33 | N=1 | O=4
| SMILES = CC(C)(C)c1cc(-c2cc(-c3ccc(C(=O)O)cc3)ccc2OCCO)ccc1N1CCCC1
| StdInChI = 1S/C29H33NO4/c1-29(2,3)25-19-23(10-12-26(25)30-14-4-5-15-30)24-18-22(11-13-27(24)34-17-16-31)20-6-8-21(9-7-20)28(32)33/h6-13,18-19,31H,4-5,14-17H2,1-3H3,(H,32,33)
| StdInChI_comment =
| StdInChIKey = MFBCDACCJCDGBA-UHFFFAOYSA-N
| density =
| density_notes =
| melting_point =
| melting_high =
| melting_notes =
| boiling_point =
| boiling_notes =
| solubility =
| sol_units =
| specific_rotation =
}}
Trifarotene, sold under the brand name Aklief, is a medication for the topical treatment of acne vulgaris.{{Cite web |date=11 October 2019 |title=Drug Trials Snapshots: Aklief |url=https://www.fda.gov/drugs/resources-information-approved-drugs/drug-trials-snapshots-aklief |url-status=live |archive-url=https://web.archive.org/web/20191119042107/https://www.fda.gov/drugs/resources-information-approved-drugs/drug-trials-snapshots-aklief |archive-date=19 November 2019 |access-date=18 November 2019 |website=U.S. Food and Drug Administration (FDA)}} {{PD-notice}} It is a retinoid;{{Cite web |date=28 October 2019 |title=Trifarotene Monograph for Professionals |url=https://www.drugs.com/monograph/trifarotene.html |url-status=live |archive-url=https://web.archive.org/web/20210304102410/https://www.drugs.com/monograph/trifarotene.html |archive-date=4 March 2021 |access-date=23 May 2021 |website=Drugs.com}} specifically, a fourth-generation selective retinoic acid receptor (RAR)-γ agonist.{{Cite journal |vauthors=Scott LJ |date=November 2019 |title=Trifarotene: First Approval |url=http://link.springer.com/10.1007/s40265-019-01218-6 |url-status=live |journal=Drugs |volume=79 |issue=17 |pages=1905–09 |doi=10.1007/s40265-019-01218-6 |pmid=31713811 |s2cid=207964653 |archive-url=https://web.archive.org/web/20210829180337/https://link.springer.com/article/10.1007%2Fs40265-019-01218-6 |archive-date=29 August 2021 |access-date=17 June 2020}}
Trifarotene was granted orphan drug designation for the treatment of congenital ichthyosis by both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).{{Cite web |date=24 December 1999 |title=Trifarotene Orphan Drug Designations and Approvals |url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=20144310 |url-status=live |archive-url=https://web.archive.org/web/20210829094902/https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=20144310 |archive-date=29 August 2021 |access-date=19 August 2020 |website=U.S. Food and Drug Administration (FDA)}}{{Cite web |date=12 August 2020 |title=EU/3/20/2264 |url=https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3202264 |url-status=live |archive-url=https://web.archive.org/web/20210109125835/https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3202264 |archive-date=9 January 2021 |access-date=19 August 2020 |website=European Medicines Agency (EMA)}} It was approved for medical use in the United States in October 2019.{{Cite web |date=7 October 2019 |title=Aklief (trifarotene) FDA Approval History |url=https://www.drugs.com/history/aklief.html |url-status=live |archive-url=https://web.archive.org/web/20201027190832/https://www.drugs.com/history/aklief.html |archive-date=27 October 2020 |access-date=19 November 2019 |website=Drugs.com}}{{Cite web |date=21 October 2019 |title=Drug Approval Package: Aklief |url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211527Orig1s000TOC.cfm |url-status=live |archive-url=https://web.archive.org/web/20191119042411/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/211527Orig1s000TOC.cfm |archive-date=19 November 2019 |access-date=18 November 2019 |website=U.S. Food and Drug Administration (FDA)}} In December 2019, its labelling and package leaflet text received a decentralised approval for 16 European countries.{{Cite press release |title=Galderma receives a positive outcome through the European Decentralised Procedure for Aklief (trifarotene 50 mcg/g cream), the first new retinoid molecule for acne in the European Union in 25 years |date=20 December 2019 |publisher=Galderma |url=https://www.businesswire.com/news/home/20191220005031/en/Galderma-receives-a-positive-outcome-through-the-European-Decentralised-Procedure-for-AKLIEF%C2%AE-trifarotene-50-mcgg-cream-the-first-new-retinoid-molecule-for-acne-in-the-European-Union-in-25-years1 |via=Business Wire |access-date=24 May 2021 |url-status=live |archive-url=https://web.archive.org/web/20210524032944/https://www.businesswire.com/news/home/20191220005031/en/Galderma-receives-a-positive-outcome-through-the-European-Decentralised-Procedure-for-AKLIEF%C2%AE-trifarotene-50-mcgg-cream-the-first-new-retinoid-molecule-for-acne-in-the-European-Union-in-25-years1 |archive-date=24 May 2021}}
Medical uses
In the United States, trifarotene is indicated for the topical treatment of acne vulgaris in people nine years of age and older. In both Canada and Australia, it is indicated for the topical treatment of acne vulgaris of the face and/or the trunk in people twelve years of age and older.
Side effects
Most adverse effects of topical trifarotene for the treatment of acne are at the location side and transient, such as application site irritation, allergic dermatitis, skin irritation and sunburn.{{cite journal | vauthors = Tan J, Thiboutot D, Popp G, Gooderham M, Lynde C, Del Rosso J, Weiss J, Blume-Peytavi U, Weglovska J, Johnson S, Parish L, Witkowska D, Sanchez Colon N, Alió Saenz A, Ahmad F, Graeber M, Stein Gold L | title = Randomized phase 3 evaluation of trifarotene 50 μg/g cream treatment of moderate facial and truncal acne | language = English | journal = Journal of the American Academy of Dermatology | volume = 80 | issue = 6 | pages = 1691–1699 | date = June 2019 | pmid = 30802558 | doi = 10.1016/j.jaad.2019.02.044 | doi-access = free }} Even though systemic absorption is very low,{{cite journal | vauthors = Wagner N, Benkali K, Alió Sáenz A, Poncet M, Graeber M | title = Clinical Pharmacology and Safety of Trifarotene, a First-in-Class RARγ-Selective Topical Retinoid | journal = Journal of Clinical Pharmacology | volume = 60 | issue = 5 | pages = 660–668 | date = May 2020 | pmid = 32017149 | pmc = 7187247 | doi = 10.1002/jcph.1566 }} use of trifarotene is still contraindicated during pregnancy{{cite journal | vauthors = | title = Trifarotene for acne | journal = Australian Prescriber | volume = 44 | issue = 4 | pages = 140–141 | date = August 2021 | pmid = 34421181 | pmc = 8377295 | doi = 10.18773/austprescr.2021.033 }} because of the known risk of teratogenicity of the overall class of drugs trifarotene belongs to, retinoids.
Society and culture
= Legal status =
References
{{reflist}}
{{Acne-treating agents}}
{{Retinoid receptor modulators}}
{{Portal bar | Medicine}}
{{Authority control}}
Category:1-Pyrrolidinyl compounds
Category:Anti-acne preparations
{{dermatologic-drug-stub}}