13-cis retinoic acid; isotretinoin (Accutane)
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Introduction
Tradename: Accutane.
Indications
Contraindications
- teratogen: contraindicated in pregnancy
- females of child-bearing age should be on a reliable method of contraception for 1 month prior to, during & after therapy
- a pregnancy test should be performed prior to initiation of therapy in all women of child-bearing age
- the manufacturer recommends 2 reliable methods of contraception
Dosage
- 0.5-2 mg/kg/day PO BID
- cystic acne
- disorders of keratinization:
- individualize doses
- doses up to 4 mg/kg/day have been used
- take with food
Low-dose: 0.1-0.2 mg/kg/day may take longer than standard dose, but fewer adverse effects
Minidose: 2.5-5 mg QD up to 6 months therapy may be necessary adverse effects are minimal
Capsules: 10, 20, 40 mg.
Monitor
- serum ALT or serum AST
- serum ALT at baseline & at peak dose[17]
- baseline & every 1-2 weeks until response to therapy established;
- thereafter every 3 months (not necessary)[17]
- increases in serum ALT or serum AST may also occur with protein supplements, exercise recovery products, excess ibuprofen, or alcohol, especially in adolescent males[15]
- lipid panel baseline & at 4 weeks
- serum triglycerides at baseline & at peak dose[17]
- continue frequent monitoring in patients with diabetes, alcohol use, or personal or family history of lipid disorder
- serum glucose baseline & periodically
- check more frequently in patients with diabetes
- pregnancy test (female)[11]
- abnormal laboratory findings occur but are rarely problematic[15]
Adverse effects
- common (> 10%)
- less common (1-10%)
- depression (cases of suicide)
- no increased risk of suicide or other psychiatric disorders[18]
- skin rash
- dry eyes
- headache
- photophobia
- skin peeling on hands & soles of feet
- dyspepsia
- fatigue
- depression (cases of suicide)
- uncommon (< 1%)
- hepatitis, ulcerative colitis[12], optic neuritis, mood changes, bleeding of gums, cataracts, pseudotumor cerebri, pruritus, hair loss, anorexia, nausea/vomiting, increased ESR, anemia
- other[2][3]
- blepharitis
- conjunctivitis
- nail dystrophy
- arthralgias
- dry nose
- increases VLDL & LDL
- decreased HDL
- lethargy
- may cause new or worsening diabetes mellitus[11]
- suicidal ideation, suicide attempt[13]
Drug interactions
- risk of pseudotumor cerebri increased by coadministration of doxycycline
Mechanism of action
- regulation of cell proliferation & differentiation
- modulation of cellular immune responses
- inhibition of sebaceous gland activity & follicular keratinization
- mediates apoptosis of sebaceous gland cells via induction of neutrophil gelatinase-associated lipocalin (NGAL) expression[10]
Notes
Prescribing physician & patients must register.
Register both men & women patients.
Document negative pregnancy tests & contraceptive methods for women.
Men are registered to insure proper counseling on side effects?
Pharmacists will access the iPledge registry to verify that the physician & the patient are registered & a negative pregnancy test is on file.
Patients must pick up the Rx within 7 days of writing.
More general terms
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ 2.0 2.1 Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 1004
- ↑ 3.0 3.1 Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 166
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998 Department of Veterans Affairs, VA National Formulary
- ↑ 6.0 6.1 Prescriber's Letter 9(8):46 2002
- ↑ An Enhanced Risk Management Program for Isotretinoin Products Prescriber's Letter 11(4):21 2004 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200404&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 8.0 8.1 Prescriber's Letter 12(9): 2005 Isotretinoin (Accutane) iPLEDGE Risk Management Program Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=210912&pb=PRL (subscription needed) http://www.prescribersletter.com iPledge: http://www.ipledgeprogram.com contact: (866) 495-0654
- ↑ FDA Medwatch http://www.fda.gov/medwatch/safety/2006/safety06.htm#Isotretinoin
- ↑ 10.0 10.1 Nelson AM, Zhao W, Gilliland KL, Zaenglein AL, Liu W, Thiboutot DM. Neutrophil gelatinase-associated lipocalin mediates 13-cis retinoic acid-induced apoptosis of human sebaceous gland cells. J Clin Invest. 2008 Apr;118(4):1468-78. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18317594
- ↑ 11.0 11.1 11.2 Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Liver Function Test Scheduling Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=260704&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 12.0 12.1 Bernstein CN et al Isotretinoin is not associated with inflammatory bowel disease: A population-based case-control study. Am J Gastroenterol 2009 Nov; 104:2774. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19623167
Shale M et al Isotretinoin and intestinal inflammation: What gastroenterologists need to know. Gut 2009 Jun; 58:737. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19433589
Crockett SD et al. Isotretinoin use and the risk of inflammatory bowel disease: A case-control study. Am J Gastroenterol 2010 Mar 30; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20354506 <Internet> http://dx.doi.org/10.1038/ajg.2010.124 - ↑ 13.0 13.1 Physician' First Watch, Nove 12, 2009 Massachusetts Medical Society http://www.jwatch.org
Sundstrom A et al Association of suicide attempts with acne and treatment with isotretinoin: retrospective Swedish cohort study BMJ 2010; 341:c5812 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21071484 <Internet> http://www.bmj.com/content/341/bmj.c5812.full - ↑ 14.0 14.1 Deprecated Reference
- ↑ 15.0 15.1 15.2 Chang MW Laboratory Monitoring During Isotretinoin Therapy for Acne: Too Much, Too Often? Physician's First Watch, Dec 21, 2015 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
Lee YH, Scharnitz TP, Muscat J et al. Laboratory monitoring during isotretinoin therapy for acne: A systematic review and meta-analysis. JAMA Dermatol 2015 Dec 2; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26630323 <Internet> http://archderm.jamanetwork.com/article.aspx?articleid=2471551 - ↑ 16.0 16.1 Opel D, Kramer ON, Chevalier M, Bigby M, Albrecht J. Not every patient needs a triglyceride check, but all can get pancreatitis: a systematic review and clinical characterization of isotretinoin-associated pancreatitis. Br J Dermatol. 2017 Oct;177(4):960-966. Epub 2017 Sep 19. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27893168
- ↑ 17.0 17.1 17.2 17.3 Brunk D Study Provides Consensus on Lab Monitoring in Patients Treated With Isotretinoin. Medscape. June 23, 2022 https://www.medscape.com/viewarticle/976116
- ↑ 18.0 18.1 Tan NKW et al. Risk of suicide and psychiatric disorders among isotretinoin users: A meta-analysis. JAMA Dermatol 2023 Nov 29; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/38019562 PMCID: PMC10687715 Free PMC article https://jamanetwork.com/journals/jamadermatology/fullarticle/2812525