| Revision as of 13:52, 10 January 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,294 edits Saving copy of the {{drugbox}} taken from revid 468307809 of page Tretinoin for the Chem/Drugbox validation project (updated: 'DrugBank'). |
Latest revision as of 14:46, 21 January 2025 edit AnomieBOT (talk | contribs)Bots6,600,238 editsm Dating maintenance tags: {{Cn}} |
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{{Short description|Medication}} |
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{{ambox | text = This page contains a copy of the infobox ({{tl|drugbox}}) taken from revid of page ] with values updated to verified values.}} |
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{{About||the isomer of tretinoin used primarily to treat more severe acne|Isotretinoin|all-trans-retinoic acid as the metabolite of vitamin A|Retinoic acid}} |
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{{Drugbox |
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{{Use dmy dates|date=December 2024}} |
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{{cs1 config |name-list-style=vanc |display-authors=6}} |
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| verifiedrevid = 459450865 |
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{{Infobox drug |
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| IUPAC_name = retinoic acid |
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| Watchedfields = changed |
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| image = Retinoic_acid.png |
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| verifiedrevid = 470612798 |
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|image2=Tretinoin molecule.png |
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| image = Tretinoin structure.svg |
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| image_class = skin-invert-image |
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| width = 275 |
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| alt = |
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| caption = |
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<!-- Clinical data --> |
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<!-- Clinical data --> |
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| pronounce = ] |
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| tradename = Avita, Renova, Retin-a |
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| tradename = Retin-A, Avita, Renova, others |
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| Drugs.com = {{drugs.com|monograph|tretinoin}} |
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| Drugs.com = {{drugs.com|monograph|tretinoin}}<br />Topical {{Drugs.com|monograph|tretinoin-topical}} |
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| MedlinePlus = a682437 |
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| MedlinePlus = a608032 |
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| licence_US = Tretinoin |
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| DailyMedID = Tretinoin |
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| pregnancy_category = C(topical), D(oral)<sub>(US)</sub>, X(oral)<sub>(Aus)</sub> |
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| pregnancy_AU = X |
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| pregnancy_AU_comment = / (Oral); D (Topical)<ref name="Drugs.com oral pregnancy">{{cite web |title=Tretinoin (Vesanoid) Use During Pregnancy |website=Drugs.com |date=25 July 2019 |url=https://www.drugs.com/pregnancy/tretinoin.html |access-date=16 January 2020}}</ref><ref name="Drugs.com topical pregnancy">{{cite web |title=Tretinoin topical Use During Pregnancy |website=Drugs.com |date=1 July 2019 |url=https://www.drugs.com/pregnancy/tretinoin-topical.html |access-date=16 January 2020}}</ref> |
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| pregnancy_category= |
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| routes_of_administration = ], ] |
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| class = |
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| ATC_prefix = D10 |
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| ATC_suffix = AD01 |
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| ATC_supplemental = {{ATC|L01|XF01}}, {{ATC|D10|AD51}} |
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<!-- Legal status --> |
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| legal_AU = S4 |
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| legal_AU = S4 |
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| legal_AU_comment = |
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| legal_BR = C2 |
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| legal_BR_comment = <ref>{{cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=31 March 2023 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=3 August 2023 |access-date=15 August 2023 |publisher=] |language=pt-BR |publication-date=4 April 2023}}</ref> |
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| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_CA_comment = |
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| legal_DE = <!-- Anlage I, II, III or Unscheduled--> |
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| legal_DE_comment = |
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| legal_NZ = <!-- Class A, B, C --> |
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| legal_NZ_comment = |
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| legal_UK = POM |
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| legal_UK = POM |
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| legal_UK_comment = |
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| legal_US = Rx-only |
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| legal_US = Rx-only |
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| legal_US_comment = <ref name="OralLabel" /><ref name="TopicalLabel" /> |
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| legal_status = |
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| legal_EU = Rx-only |
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| routes_of_administration = Topical, oral |
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| legal_EU_comment = <ref>{{cite web |title=List of nationally authorised medicinal products:Active substance(s): tretinoin (oral formulations) |url=https://www.ema.europa.eu/en/documents/psusa/tretinoin-oral-formulations-list-nationally-authorised-medicinal-products-psusa/00003015/202203_en.pdf |website=ema.europa.eu |publisher=European Medicines Agency |archive-url=https://web.archive.org/web/20230130131600/https://www.ema.europa.eu/en/documents/psusa/tretinoin-oral-formulations-list-nationally-authorised-medicinal-products-psusa/00003015/202203_en.pdf |archive-date=30 January 2023 |date=1 December 2022 |url-status=live}}</ref> |
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| DailyMedID = 54982 |
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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV--> |
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| legal_UN_comment = |
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| legal_status = <!--For countries not listed above--> |
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<!-- Pharmacokinetic data --> |
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<!-- Pharmacokinetic data --> |
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| bioavailability = |
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| bioavailability = |
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| protein_bound = > 95% |
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| protein_bound = > 95% |
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| metabolism = |
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| metabolism = |
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| metabolites = |
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| elimination_half-life = 0.5-2 hours |
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| onset = |
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| elimination_half-life = 0.5–2 hours |
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| duration_of_action = |
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| excretion = |
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<!-- Identifiers --> |
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<!-- Identifiers --> |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| CAS_number_Ref = {{cascite|correct|cas}} |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 302-79-4 |
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| CAS_number = 302-79-4 |
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| CAS_supplemental = |
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| ATC_prefix = D10 |
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| ATC_suffix = AD01 |
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| ATC_supplemental = {{ATC|L01|XX14}} |
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| PubChem = 444795 |
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| PubChem = 444795 |
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| IUPHAR_ligand = 2644 |
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| DrugBank_Ref = {{drugbankcite|changed|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = DB00755 |
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| DrugBank = DB00755 |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = D00094 |
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| KEGG = D00094 |
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| KEGG2_Ref = {{keggcite|correct|kegg}} |
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| KEGG2 = C00777 |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| ChEBI_Ref = {{ebicite|correct|EBI}} |
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| ChEBI = 15367 |
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| ChEBI = 15367 |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 38 |
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| ChEMBL = 38 |
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| NIAID_ChemDB = |
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| PDB_ligand = |
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| synonyms = ATRA |
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<!-- Chemical data --> |
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<!-- Chemical and physical data --> |
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| IUPAC_name = (2''E'',4''E'',6''E'',8''E'')-3,7-Dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraenoic acid |
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| C=20 | H=28 | O=2 |
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| C=20 | H=28 | O=2 |
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| molecular_weight = 300.4412 g/mol |
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| smiles = O=C(O)\C=C(\C=C\C=C(\C=C\C1=C(\CCCC1(C)C)C)C)C |
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| SMILES = CC1=C(C(CCC1)(C)C)C=CC(=CC=CC(=CC(=O)O)C)C |
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| InChI = 1/C20H28O2/c1-15(8-6-9-16(2)14-19(21)22)11-12-18-17(3)10-7-13-20(18,4)5/h6,8-9,11-12,14H,7,10,13H2,1-5H3,(H,21,22)/b9-6+,12-11+,15-8+,16-14+ |
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| InChIKey = SHGAZHPCJJPHSC-YCNIQYBTBL |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChI = 1S/C20H28O2/c1-15(8-6-9-16(2)14-19(21)22)11-12-18-17(3)10-7-13-20(18,4)5/h6,8-9,11-12,14H,7,10,13H2,1-5H3,(H,21,22)/b9-6+,12-11+,15-8+,16-14+ |
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| StdInChI = 1S/C20H28O2/c1-15(8-6-9-16(2)14-19(21)22)11-12-18-17(3)10-7-13-20(18,4)5/h6,8-9,11-12,14H,7,10,13H2,1-5H3,(H,21,22)/b9-6+,12-11+,15-8+,16-14+ |
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| StdInChI_comment = |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = SHGAZHPCJJPHSC-YCNIQYBTSA-N |
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| StdInChIKey = SHGAZHPCJJPHSC-YCNIQYBTSA-N |
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| density = |
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| density_notes = |
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| melting_point = 180 |
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| melting_point = 180 |
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| melting_high = |
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| melting_notes = |
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| boiling_point = |
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| boiling_notes = |
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| solubility = |
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| specific_rotation = |
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}} |
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}} |
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<!-- Definition and medical uses --> |
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'''Tretinoin''', also known as '''all-''trans'' retinoic acid''' ('''ATRA'''), is a ] used for the treatment of ] and ].<ref name="AHFS2016" /><ref name="Tiv2016">{{cite book | vauthors = Tivnan A |title=Resistance to Targeted Therapies Against Adult Brain Cancers |date=2016 |publisher=Springer |isbn=978-3-319-46505-0 |page=123 |url=https://books.google.com/books?id=XaCYDQAAQBAJ&pg=PA123 |url-status=live |archive-url=https://web.archive.org/web/20171105200032/https://books.google.ca/books?id=XaCYDQAAQBAJ&pg=PA123 |archive-date=5 November 2017}}</ref><ref name="BNF69">{{cite book |title=British national formulary : BNF 69 |date=2015 |publisher=British Medical Association |isbn=978-0-85711-156-2 |pages=627, 821–822 |edition=69}}</ref> For acne, it is applied to the skin as a cream, gel or ointment.<ref name="BNF69" /> For acute promyelocytic leukemia, it is effective only when the RARA-PML fusion mutation is present<ref>{{cite journal | vauthors = Yoshida H, Kitamura K, Tanaka K, Omura S, Miyazaki T, Hachiya T, Ohno R, Naoe T | title = Accelerated degradation of PML-retinoic acid receptor alpha (PML-RARA) oncoprotein by all-trans-retinoic acid in acute promyelocytic leukemia: possible role of the proteasome pathway | journal = Cancer Research | volume = 56 | issue = 13 | pages = 2945–2948 | date = July 1996 | pmid = 8674046 }}</ref> and is taken by mouth for up to three months.<ref name="AHFS2016">{{cite web |title=Tretinoin |url=https://www.drugs.com/monograph/tretinoin.html |publisher=The American Society of Health-System Pharmacists |access-date=8 December 2016 |url-status=live |archive-url=https://web.archive.org/web/20161130124932/https://www.drugs.com/monograph/tretinoin.html |archive-date=30 November 2016}}</ref> Topical tretinoin is also the most extensively investigated retinoid therapy for ].<ref>{{cite web|title=Retinoids, topical|date=|publisher=American Osteopathic College of Dermatology|url=https://www.aocd.org/page/Retinoidstopical}}</ref> |
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<!-- Side effects and mechanism --> |
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Common side effects when used as a cream are limited to the skin and include skin redness, peeling, and sun sensitivity.<ref name="BNF69" /> When taken by mouth, side effects include ], ], ], headache, numbness, depression, skin dryness, itchiness, hair loss, vomiting, muscle pains, and vision changes.<ref name="AHFS2016" /> Other severe side effects include ] and ].<ref name="AHFS2016" /> Use during ] is contraindicated due to the risk of birth defects.<ref name="AHFS2016" /><ref name="Drugs.com oral pregnancy" /> It is in the ] family of medications.<ref name="Tiv2016" /> |
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<!-- History and culture --> |
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Tretinoin was patented in 1957 and approved for medical use in 1962.<ref name="Fis2006">{{cite book | vauthors = Fischer J, Ganellin CR |title= Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=978-3-527-60749-5 |page=476 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA476 |url-status=live |archive-url=https://web.archive.org/web/20171105200032/https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA476 |archive-date=5 November 2017}}</ref> It is on the ].<ref name="WHO21st">{{cite book |vauthors=((World Health Organization)) |title=World Health Organization model list of essential medicines: 21st list 2019 |year=2019 |hdl=10665/325771 |author-link=World Health Organization |publisher=World Health Organization |location=Geneva |id=WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO |hdl-access=free}}</ref> Tretinoin is available as a ].<ref name="AHFS2016B">{{cite web |title=Tretinoin topical |url=https://www.drugs.com/monograph/tretinoin-topical.html |publisher=The American Society of Health-System Pharmacists |access-date=8 December 2016 |url-status=live |archive-url=https://web.archive.org/web/20160516200244/http://www.drugs.com/monograph/tretinoin-topical.html |archive-date=16 May 2016}}</ref> In 2022, it was the 238th most commonly prescribed medication in the United States, with more than 1{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Tretinoin Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Tretinoin | access-date = 30 August 2024 }}</ref> |
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== Medical uses == |
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=== Skin use === |
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==== Acne ==== |
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Tretinoin is most commonly used to treat ],<ref name="TopicalLabel" /> both inflammatory and noninflammatory. Multiple studies support the efficacy of topical retinoids in the treatment of acne vulgaris.<ref>{{cite journal |vauthors=Leyden JJ, Shalita A, Thiboutot D, Washenik K, Webster G |title=Topical retinoids in inflammatory acne: a retrospective, investigator-blinded, vehicle-controlled, photographic assessment |journal=Clinical Therapeutics |volume=27 |issue=2 |pages=216–24 |date=February 2005 |pmid=15811485 |doi=10.1016/j.clinthera.2005.02.009}}</ref><ref>{{cite journal |vauthors=Webster G, Cargill DI, Quiring J, Vogelson CT, Slade HB |title=A combined analysis of 2 randomized clinical studies of tretinoin gel 0.05% for the treatment of acne |journal=Cutis |volume=83 |issue=3 |pages=146–54 |date=March 2009 |pmid=19363908}}</ref> It is sometimes used in conjunction with other topical acne medications to enhance their penetration.<ref name="pmid12833004">{{cite journal |vauthors=Gollnick H, Cunliffe W, Berson D, Dreno B, Finlay A, Leyden JJ, Shalita AR, Thiboutot D |title=Management of acne: a report from a Global Alliance to Improve Outcomes in Acne |journal=Journal of the American Academy of Dermatology |volume=49 |issue=1 Suppl |pages=S1-37 |date=July 2003 |pmid=12833004 |doi=10.1067/mjd.2003.618 | collaboration = Global Alliance to Improve Outcomes in Acne}}</ref> In addition to treating active acne, retinoids accelerate the resolution of acne-induced ].<ref name="Kang S 2008">{{cite book | vauthors = Kang S, Voorhees JJ | chapter = Topical retinoids. | title = Fitzpatrick's Dermatology in General Medicine | edition = 7th | veditors = Wolff K, Goldsmith LA, Katz SI, etal | publisher = McGraw Hill | location = New York | date = 2008 | page = 2106 }}</ref> It is also useful as maintenance therapy for people who have responded well to their initial treatment, reducing the prolonged use of antibiotics for acne.<ref>{{cite journal | vauthors = Leyden J, Stein-Gold L, Weiss J | title = Why Topical Retinoids Are Mainstay of Therapy for Acne | journal = Dermatology and Therapy | volume = 7 | issue = 3 | pages = 293–304 | date = September 2017 | pmid = 28585191 | pmc = 5574737 | doi = 10.1007/s13555-017-0185-2 }}</ref> |
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==== Photoaging ==== |
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] is premature skin aging resulting from prolonged and repeated exposure to solar radiation. Features of photoaging include fine and coarse wrinkles, changes in skin pigmentation, and loss of elasticity. In human skin, topical retinoids increase collagen production, induce epidermal hyperplasia, and decrease ] and ] atypia. Topical tretinoin is the most extensively investigated retinoid therapy for photoaging.<ref>{{cite journal |vauthors=Han A, Chien AL, Kang S |title=Photoaging |journal=Dermatologic Clinics |volume=32 |issue=3 |pages=291–9, vii |date=July 2014 |pmid=24891052 |doi=10.1016/j.det.2014.03.015}}</ref> Topical tretinoin can be used for mild to severe photoaging in people of all skin types. Several weeks or months of use are typically required before improvement is appreciated. Although it has only been studied for up to two years, it may be continued indefinitely. A long-term maintenance regimen with a lower concentration or less frequent application may be an alternative to continued use.<ref>{{cite journal |vauthors=Kang S, Bergfeld W, Gottlieb AB, Hickman J, Humeniuk J, Kempers S, Lebwohl M, Lowe N, McMichael A, Milbauer J, Phillips T, Powers J, Rodriguez D, Savin R, Shavin J, Sherer D, Silvis N, Weinstein R, Weiss J, Hammerberg C, Fisher GJ, Nighland M, Grossman R, Nyirady J |title=Long-term efficacy and safety of tretinoin emollient cream 0.05% in the treatment of photodamaged facial skin: a two-year, randomized, placebo-controlled trial |journal=American Journal of Clinical Dermatology |volume=6 |issue=4 |pages=245–53 |date=2005 |pmid=16060712 |doi=10.2165/00128071-200506040-00005 |s2cid=40127961}}</ref> |
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=== Leukemia === |
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Tretinoin is used to induce remission in people with ] (APL) who have a mutation (the t(15;17) translocation that gives rise to the PML::RARα fusion gene). It is not used for maintenance therapy.<ref name="OralLabel">{{cite web |title=Tretinoin capsule |website=DailyMed |date=12 December 2018 |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=264138c1-9e5f-45ef-be87-79ca97c989d9 |access-date=16 January 2020}}</ref><ref>{{cite journal |vauthors=Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wang ZY |title=Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia |journal=Blood |volume=72 |issue=2 |pages=567–72 |date=August 1988 |pmid=3165295 |doi=10.1182/blood.V72.2.567.567 |url=http://www.bloodjournal.org/cgi/reprint/72/2/567.pdf|doi-access=free }}</ref><ref>{{cite journal |vauthors=Castaigne S, Chomienne C, Daniel MT, Ballerini P, Berger R, Fenaux P, Degos L |title=All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical results |journal=Blood |volume=76 |issue=9 |pages=1704–9 |date=November 1990 |pmid=2224119 |doi=10.1182/blood.V76.9.1704.1704 |url=http://www.bloodjournal.org/cgi/reprint/76/9/1704.pdf|doi-access=free }}</ref> |
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Tretinoin is not effective for the treatment of non-APL forms of ]<ref>{{cite journal |vauthors=Küley-Bagheri Y, Kreuzer KA, Monsef I, Lübbert M, Skoetz N |title=Effects of all-trans retinoic acid (ATRA) in addition to chemotherapy for adults with acute myeloid leukaemia (AML) (non-acute promyelocytic leukaemia (non-APL)) |journal=The Cochrane Database of Systematic Reviews |volume=2018 |pages=CD011960 |date=August 2018 |issue=8 |pmid=30080246 |pmc=6513628 |doi=10.1002/14651858.CD011960.pub2 | collaboration = Cochrane Haematological Malignancies Group}}</ref> or other forms of leukemia. Preclinical studies and clinical data analysis suggest that retinoic acid promotes the growth of ].<ref>{{cite journal | vauthors = Ono Y, Fukuhara N, Yoshie O | title = TAL1 and LIM-only proteins synergistically induce retinaldehyde dehydrogenase 2 expression in T-cell acute lymphoblastic leukemia by acting as cofactors for GATA3 | journal = Molecular and Cellular Biology | volume = 18 | issue = 12 | pages = 6939–6950 | date = December 1998 | pmid = 9819382 | pmc = 109277 | doi = 10.1128/MCB.18.12.6939 }}</ref> |
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== Side effects == |
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=== Dermatology === |
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Topical tretinoin is for use only on the skin and should not be applied to eyes or mucosal tissues. Common side effects include skin irritation, redness, swelling, and blistering.<ref name="TopicalLabel">{{cite web |title=Tretinoin Cream- tretinoin cream |website=DailyMed |date=1 December 2018 |url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=745cc3ce-60b4-4479-a055-316817567949 |access-date=16 January 2020}}</ref> If irritation is a problem, a decrease in the frequency of application to every other or every third night can be considered, and the frequency of application can be increased as tolerance improves. The fine skin flaking that is often seen can be gently exfoliated with a washcloth. A non-comedogenic facial moisturizer can also be applied if needed. Delaying the application of the retinoid for at least 20 minutes after washing and drying the face may also be helpful. Topical retinoids are not true photosensitizing drugs, but people using topical retinoids have described symptoms of increased sun sensitivity. This is thought to be due to the thinning of the ] leading to a decreased barrier against ultraviolet light exposure, as well as an enhanced sensitivity due to the presence of cutaneous irritation.<ref>{{cite journal |vauthors=Zaenglein AL |title=Topical retinoids in the treatment of acne vulgaris |journal=Seminars in Cutaneous Medicine and Surgery |volume=27 |issue=3 |pages=177–82 |date=September 2008 |pmid=18786495 |doi=10.1016/j.sder.2008.06.001}}</ref> |
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=== Acute Promyelocytic Leukemia === |
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The oral form of the drug has ]s concerning the risks of ] and ].<ref name="OralLabel" /> Other significant side effects include a risk of ], ] in children, high lipids (] and/or ]), and liver damage.<ref name="OralLabel" /> |
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There are many significant side effects from this drug that include malaise (66%), shivering (63%), hemorrhage (60%), infections (58%), peripheral edema (52%), pain (37%), chest discomfort (32%), edema (29%), disseminated intravascular coagulation (26%), weight increase (23%), injection site reactions (17%), anorexia (17%), weight decrease (17%), and myalgia (14%).<ref name="OralLabel" /> |
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Respiratory side effects usually signify ] syndrome, and include upper respiratory tract disorders (63%), dyspnea (60%), respiratory insufficiency (26%), pleural effusion (20%), pneumonia (14%), rales (14%), and expiratory wheezing (14%), and many others at less than 10%.<ref name="OralLabel" /> Around 23% of people taking the drug have reported earache or a feeling of fullness in their ears.<ref name="OralLabel" /> Gastrointestinal disorders include bleeding (34%), abdominal pain (31%), diarrhea (23%), constipation (17%), dyspepsia (14%), and swollen belly (11%) and many others at less than 10%.<ref name="OralLabel" /> |
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Cardiovascular side effects include arrhythmias (23%), flushing (23%), hypotension (14%), hypertension (11%), ] (11%), and cardiac failure (6%) and for 3% of patients: cardiac arrest, myocardial infarction, enlarged heart, heart murmur, ischemia, stroke, myocarditis, pericarditis, pulmonary hypertension, secondary cardiomyopathy.<ref name="OralLabel" /> |
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In the nervous system, side effects include dizziness (20%), ] (17%), anxiety (17%), insomnia (14%), depression (14%), confusion (11%), and many others at less than 10% frequency.<ref name="OralLabel" /> |
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In the urinary system, side effects include ] (11%) and several others at less than 10% frequency.<ref name="OralLabel" /> |
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== Mechanism of action == |
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For its use in Acute Promyelocytic Leukemia, tretinoin causes the RARA:PML fusion oncogene to degrade, resulting in the loss of the key driver oncogene.<ref>{{cite journal | vauthors = Yoshida H, Kitamura K, Tanaka K, Omura S, Miyazaki T, Hachiya T, Ohno R, Naoe T | title = Accelerated degradation of PML-retinoic acid receptor alpha (PML-RARA) oncoprotein by all-trans-retinoic acid in acute promyelocytic leukemia: possible role of the proteasome pathway | journal = Cancer Research | volume = 56 | issue = 13 | pages = 2945–2948 | date = July 1996 | pmid = 8674046 | url = https://pubmed.ncbi.nlm.nih.gov/8674046/ }}</ref> This degradation allows the blasts to mature and results in dramatic responses. This response is typically short-lived as Cyp26 genes are rapidly upregulated to degrade tretinoin. The RARA:PML oncogene is not present in other cancer types, thus explaining why tretinoin and other ]s have not been effective across hundreds of different trials.<ref>{{cite journal | vauthors = Esposito M, Amory JK, Kang Y | title = The pathogenic role of retinoid nuclear receptor signaling in cancer and metabolic syndromes | journal = The Journal of Experimental Medicine | volume = 221 | issue = 9 | date = September 2024 | pmid = 39133222 | doi = 10.1084/jem.20240519 | doi-access = free | pmc = 11318670 }}</ref> |
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For its use in acne, tretinoin (along with other retinoids) are vitamin A derivatives that act by binding to two nuclear receptor families within keratinocytes: the ]s (RAR) and the ]s (RXR).<ref name="Kang S 2008" /> These events contribute to the normalization of follicular keratinization and decreased cohesiveness of ]s, resulting in reduced follicular occlusion and microcomedone formation.<ref>Fernandez EM, Zaenglein A, Thiboutot D. Acne Treatment Methodologies. In: Cosmetic Formulation of Skin Care Products, Taylor and Francis Group, New York 2006. p.273.</ref> The retinoid-receptor complex competes for coactivator proteins of AP-1, a key transcription factor involved in inflammation.<ref name="Kang S 2008" /> Retinoids also down-regulate expression of toll-like receptor (TLR)-2, which has been implicated in the inflammatory response in acne.<ref>{{cite journal |vauthors=Liu PT, Krutzik SR, Kim J, Modlin RL |title=Cutting edge: all-trans retinoic acid down-regulates TLR2 expression and function |journal=Journal of Immunology |volume=174 |issue=5 |pages=2467–70 |date=March 2005 |pmid=15728448 |doi=10.4049/jimmunol.174.5.2467 |s2cid=20740543 |doi-access=free}}</ref> Moreover, tretinoin and retinoids may enhance the penetration of other topical acne medications.<ref name="pmid12833004" /> |
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The combination of the 10% ] and light results in more than 50% degradation of tretinoin in about 2 hours and 95% in 24 hours.<ref name="Wiley 1998 pp. 8–11">{{cite journal | vauthors = Martin B, Meunier C, Montels D, Watts O | title = Chemical stability of adapalene and tretinoin when combined with benzoyl peroxide in presence and in absence of visible light and ultraviolet radiation | journal = The British Journal of Dermatology | volume = 139 | issue = Suppl 52 | pages = 8–11 | date = October 1998 | pmid = 9990414 | doi = 10.1046/j.1365-2133.1998.1390s2008.x | publisher = Wiley | s2cid = 43287596 }}</ref> This lack of stability in the presence of light and oxidizing agents has led to the development of novel formulations of the drug. When ] tretinoin is exposed to benzoyl peroxide and light only 1% degradation takes place in about 4 hours and only 13% after 24 hours.<ref>{{cite web|title=The Stability of Tretinoin in Tretinoin Gel Microsphere 0.1%|url=https://www.mdedge.com/dermatology/article/66872/acne/stability-tretinoin-tretinoin-gel-microsphere-01|access-date=14 May 2021|website=www.mdedge.com|language=en}}</ref> |
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The biological mechanism behind triglyceride and cholesterol elevations remains under investigation.{{cn|date=January 2025}} |
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== Synthesis == |
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] |
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All-trans retinoic acid is produced by the body from dietary factors including retinol, retinyl esters or ]. The beta-carotene is first cleaved by ] to retinol which is subsequently oxidized by RDH and ALDH enzymes to produce all-trans retinoic acid (see ]). Tretinoin is produced synthetically using standard industrial practices.<ref>{{Cite web |title=WIPO - Search International and National Patent Collections |url=https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2012155796 |access-date=15 August 2024 |website=patentscope.wipo.int}}</ref> |
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== History == |
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Tretinoin was co-developed for its use in acne by ] and ] when they were at ] in the 1960s.<ref name="FultonObit">{{cite web | work = Vivant Pharmaceuticals, LLC Press Release | date = 10 July 2013 | url = http://vivantskin.blogspot.com/2013/07/vivant-skin-care-co-founder-james-e.html | title = Vivant Skin Care Co-founder James E. Fulton, MD, Loses Colon Cancer Battle | archive-url = https://web.archive.org/web/20160418081737/http://vivantskin.blogspot.com/2013/07/vivant-skin-care-co-founder-james-e.html | archive-date = 18 April 2016 }}</ref><ref name="KligmanObit">{{cite web | vauthors = Gellene D |work=The New York Times |date=22 February 2010 |url=https://www.nytimes.com/2010/02/23/us/23kligman.html?_r=0 |title=Dr. Albert M. Kligman, Dermatologist, Dies at 93}}</ref> Phase I trials, the first conducted on human subjects, were performed on inmates at ] during a long-running regime of non-therapeutic and unethical ].<ref>{{cite book | vauthors = Washington HA |url=https://www.worldcat.org/oclc/61131882 |title=Medical apartheid : the dark history of medical experimentation on Black Americans from colonial times to the present |date=2006 |publisher=Doubleday |isbn=0-385-50993-6 |location=New York |oclc=61131882}}</ref><ref>{{cite book | vauthors = Hornblum AM |url=https://www.worldcat.org/oclc/37884781 |title=Acres of skin : human experiments at Holmesburg Prison : a story of abuse and exploitation in the name of medical science |date=1998 |publisher=Routledge |isbn=0-415-91990-8 |location=New York |oclc=37884781}}</ref> The University of Pennsylvania held the patent for Retin-A, which it licensed to pharmaceutical companies.<ref name="KligmanObit" /> |
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Treatment of acute promyelocytic leukemia was first introduced at ] in Shanghai by ] in a 1988 clinical trial.<ref>{{cite journal |vauthors=Huang ME, Ye YC, Chen SR, Chai JR, Lu JX, Zhoa L, Gu LJ, Wang ZY |title=Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia |journal=Blood |volume=72 |issue=2 |pages=567–72 |date=August 1988 |pmid=3165295 |doi=10.1182/blood.V72.2.567.567 |doi-access=free}}</ref> |
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== Etymology == |
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The origin of the name ''tretinoin'' is uncertain,<ref name="MW_Medical" /><ref name="OxfordDictionaries">{{Citation| title = Tretinoin |work = Oxford Dictionaries Online |publisher=Oxford University Press |url=https://www.oxfordreference.com/display/10.1093/oi/authority.20110803105624146 }}</ref> although several sources agree (one with probability,<ref name="MW_Medical" />< one with asserted certainty<ref name="AHD">{{Citation |author=Houghton Mifflin Harcourt |title=The American Heritage Dictionary of the English Language |publisher=Houghton Mifflin Harcourt |url=https://ahdictionary.com/ |postscript=. |url-status=dead |archive-url=https://web.archive.org/web/20150925104737/https://ahdictionary.com/ |archive-date=25 September 2015 |access-date=24 January 2015}}</ref>) that it probably comes from '']-'' + ''] '' + '']'', which is plausible given that tretinoin is the ] of ]. The name '']'' is the same root ''tretinoin'' plus the prefix '']-''. Regarding pronunciation, the following variants apply equally to both ''tretinoin'' and ''isotretinoin''. Given that ''retinoic'' is pronounced {{IPAc-en|ˌ|r|ɛ|t|ɪ|ˈ|n|oʊ|ɪ|k}},<ref name="OxfordDictionaries" /><ref name="AHD" /><ref name="MW_Medical">{{Citation |title= Tretinoin | work = Merriam-Webster's Medical Dictionary |publisher=Merriam-Webster |url=https://www.merriam-webster.com/dictionary/tretinoin |postscript=.}}</ref><ref name="Dorlands">{{Citation |title= Tretinoin |work = Dorland's Illustrated Medical Dictionary |publisher=Elsevier |url=https://www.dorlandsonline.com/dorland/definition?id=50812 |postscript=.}}</ref> it is ] that {{IPAc-en|ˌ|t|r|ɛ|t|ɪ|ˈ|n|oʊ|ɪ|n}} is a commonly heard pronunciation. Dictionary transcriptions also include {{IPAc-en|ˌ|t|r|ɪ|ˈ|t|ɪ|n|oʊ|ɪ|n}} ({{respell|tri|TIN|oh|in}})<ref name="OxfordDictionaries" /><ref name="MW_Medical" /> and {{IPAc-en|ˈ|t|r|ɛ|t|ɪ|n|ɔɪ|n}}.<ref name="AHD" /><ref name="Dorlands" /> |
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== Hair loss == |
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Tretinoin has been explored as a treatment for hair loss, potentially as a way to increase the ability of ] (by acting as an enzyme and accelerating the production of minoxidil sulfate) to penetrate the scalp, but the evidence is weak and contradictory.<ref>{{cite book | vauthors = Trüeb RM | chapter = Diagnosis and Treatment |title=The Difficult Hair Loss Patient: Guide to Successful Management of Alopecia and Related Conditions. |date=2015 |publisher=Springer |location=Cham |isbn=978-3-319-19701-2 | chapter-url = https://books.google.com/books?id=0ue5BAAAQBAJ&pg=PA95 | archive-url= https://web.archive.org/web/20171105200032/https://books.google.com/books?id=0ue5BAAAQBAJ&pg=PA95 | archive-date=5 November 2017}}</ref><ref>{{cite journal |vauthors=Rogers NE, Avram MR |title=Medical treatments for male and female pattern hair loss |journal=Journal of the American Academy of Dermatology |volume=59 |issue=4 |pages=547–66; quiz 567–8 |date=October 2008 |pmid=18793935 |doi=10.1016/j.jaad.2008.07.001}}</ref> |
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== References == |
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{{Reflist}} |
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== External links == |
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* {{cite web |title=Tretinoin Topical |website=MedlinePlus |url=https://medlineplus.gov/druginfo/meds/a682437.html}} |
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