Isotretinoin

For the isomer of isotretinoin primarily used topically to treat less severe acne, see Tretinoin.

Isotretinoin
Clinical data
PronunciationSee note at tretinoin
Trade namesAccutane, Roaccutane, others[1]
AHFS/Drugs.comMonograph
MedlinePlusa681043
License data
Pregnancy
category
  • AU: X (High risk)
Routes of
administration		By mouth, topical
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityVariable
Protein binding99.9%
MetabolismLiver
Elimination half-life10–20 hours
ExcretionKidney and feces
Identifiers
  • (2Z,4E,6E,8E)-3,7-Dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraenoic acid
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.022.996 Edit this at Wikidata
Chemical and physical data
FormulaC20H28O2
Molar mass300.442 g·mol−1
3D model (JSmol)
  • O=C(O)\C=C(/C=C/C=C(/C=C/C1=C(/CCCC1(C)C)C)C)C
  • InChI=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- checkY
  • Key:SHGAZHPCJJPHSC-XFYACQKRSA-N checkY
  (verify)

Isotretinoin, also known as 13-cis-retinoic acid and sold under the brand name Accutane among others, is a medication used to treat skin diseases like harlequin-type ichthyosis, and lamellar ichthyosis, and severe cystic acne or moderate acne that is unresponsive to antibiotics.[6] Isotretinoin is used off-label to treat basal cell carcinoma and squamous cell carcinoma, although clinical evidence suggests it is not effective in this setting.[7] It is a retinoid, meaning it is related to vitamin A, and is found in small quantities naturally in the body. Its isomer, tretinoin, is also an acne drug.

The most common adverse effects are dry lips (cheilitis), dry and fragile skin (xeroderma), dry eyes[8] and an increased susceptibility to sunburn. Uncommon and rare side effects include muscle aches and pains (myalgias), and headaches. Some of those side effects can persist long after the discontinuation of use of the drug.[8] Isotretinoin may cause liver failure, therefore the patient's blood levels should be regularly tested.[9] It is known to cause birth defects due to in-utero exposure because of the molecule's close resemblance to retinoic acid, a natural vitamin A derivative that controls normal embryonic development. It is associated with psychiatric side effects, most commonly depression but also, more rarely, psychosis and unusual behaviors. Other rare side effects include hyperostosis and premature epiphyseal closure, which have been reported to be persistent.

Isotretinoin was patented in 1969 and approved for medical use in 1982.[10] In 2021, it was the 264th most commonly prescribed medication in the United States, with more than 1 million prescriptions.[11][12]

  1. ^ Cite error: The named reference brands was invoked but never defined (see the help page).
  2. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  3. ^ "Product. Roaccutane PI". guildlink.com.au.
  4. ^ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 15 August 2023.
  5. ^ "List of nationally authorised medicinal products" (PDF). European Medicines Agency. 1 December 2022. Retrieved 25 December 2022.
  6. ^ Mohiuddin AK (2019). "A Comprehensive Review of Acne Vulgaris". Journal of Clinical Pharmacy. 1 (1): 17–45.
  7. ^ Clouser MC, Roe DJ, Foote JA, Harris RB, Alberts DS (5 November 2010). "Dose response of retinol and isotretinoin in the prevention of nonmelanoma skin cancer recurrence". Nutrition and Cancer. 62 (8): 1058–1066. doi:10.1080/01635581.2010.492089. PMC 4104190. PMID 21058193.
  8. ^ a b Moy A, McNamara NA, Lin MC (September 2015). "Effects of Isotretinoin on Meibomian Glands". Optometry and Vision Science. 92 (9): 925–930. doi:10.1097/OPX.0000000000000656. PMID 26154692.
  9. ^ Erşan M (5 September 2017). "Sivilce ilacı karaciğerini mahvetti" [Acne drug destroyed her life]. www.hurriyet.com.tr (in Turkish). Retrieved 20 June 2024. [Prof. Dr. K. Yalçın Polat, President of the Department of General Surgery at the Memorial Ataşehir Hospital: Our patient's blood values were very high when she was hospitalized. It was not easy for us to decide to have a liver transplant. During our three-week treatment, her liver values continued to rise and she entered liver failure, which made us take this decision. In the liver biopsy, we saw necrosis (non-living tissue) in the liver. If we had waited a little longer, she would have fallen into a coma and we would have then lost the patient. The cause of her liver failure is the medication she takes for acne. Unfortunately, this drug is very widely used. Liver enzymes should be closely monitored while taking isotretinoin. Every kind of drug reaches the liver, and each of them has side effects as well as its positive effects. Even if the liver tolerates these and cleans the toxins, it can still be affected as in the case of Mrs. Çilingir.]
  10. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 476. ISBN 978-3-527-60749-5.
  11. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  12. ^ "Isotretinoin - Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.