      Document 0034
 DOCN  DRG0034
 UNIQUE IDENTIFIER        DRG-0213
 NAME OF SUBSTANCE        Isotretinoin [USAN 1996]
 REGISTRY NUMBER          4759-48-2
 STANDARD CHEMICAL NAME   Retinoic acid, 13-cis- [USAN 1996]
 SYNONYMS                 Accutane [USAN 1996]
 SYNONYMS                 Isotrex [USAN 1996]
 SYNONYMS                 13-cis-Retinoic acid [CHEMLINE]
 SYNONYMS                 Teriosal [Merck Index 1989]
 SYNONYMS                 13-RA [CHEMLINE]
 SYNONYMS                 3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen--
                          1-yl)2-cis-4-trans-6-trans-8-trans-nonatetran-
                          oic acid [USAN 1996]
 SYNONYMS                 Roaccutane [CHEMLINE]
 SYNONYMS                 13-cis-Vitamin A acid [CHEMLINE]
 PROTOCOL ID NUMBERS      NIAID ACTG 216
 SECONDARY SOURCE ID      Ro 4-3780 [USAN 1996]
 SECONDARY SOURCE ID      CCRIS 4286 [CHEMLINE]
 SECONDARY SOURCE ID      HSDB 3929 [CHEMLINE]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Inhibits sebaceous gland
                          function and keratinization. Isotretinoin is
                          99 percent bound in human plasma almost
                          exclusively to albumin. Terminal elimination
                          half-life ranges from 10 to 20 hours from
                          oral administration of 80 mg (capsules). The
                          major identifiable metabolite in blood is
                          4-oxo-isotretinoin, which has a mean
                          elimination half-life of 25 hours (range
                          17-50 hours). Oral absorption of isotretinoin
                          increases when taken with food or milk. [PDR
                          1995]
 DISEASES STUDIED/TREATED Treatment of anal neoplasia secondary to
                          anogenital human papillomavirus infection
                          [NIAID ACTG 216]
 CLASSIFICATION CODE      Keratolytic [USAN 1996]
 OTHER MAJOR USES         Treatment of acne vulgaris, cystic acne, and
                          several other skin diseases [AHFS Drug
                          Information 1995] [PDR 1995]
 SUBSTANCE INTERACTIONS   Concurrent use of etretinate, tretinoin or
                          vitamin A may result in additive toxic
                          effects; concurrent tetracyclines  may
                          increase the potential for the development of
                          pseudotumor cerebri. [USP DI 1995]
 ADVERSE EFFECTS          Adverse effects include major fetal
                          abnormalities, cheilitis, conjunctivitis,
                          pseudotumor cerebri (benign intracranial
                          hypertension), skeletal hyperostosis,
                          musculoskeletal symptoms including
                          arthralgia, decreased night vision, corneal
                          opacities, inflammatory bowel disease,
                          changes in serum lipid levels,
                          hepatotoxicity, transient chest pain, rash,
                          and thinning of hair. Less frequent adverse
                          effects include peeling of palms and soles,
                          skin infections, nonspecific urogenital
                          findings and gastrointestinal symptoms,
                          fatigue, headache, depression, and increased
                          susceptibility to sunburn. CNS reactions
                          (seizures, emotional instability, dizziness,
                          nervousness, drowsiness, malaise, etc.) have
                          been reported but may not be related to
                          therapy. [PDR 1995]
 CONTRAINDICATIONS        Strongly contraindicated in pregnant and
                          nursing women and in those who may become
                          pregnant while on therapy. Also
                          contraindicated in patients with sensitivity
                          to parabens, to vitamin A, and to other
                          retinoids. [PDR 1995] [AHFS Drug Information
                          1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Retinoid [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C20H28O2 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 300.44 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 174-175 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Insoluble in water, sparingly
                          soluble in alcohol [AHFS Drug Information
                          1995]
 CHEMICAL/PHYSICAL DATA   STABILITY: Photosensitive and degrades when
                          exposed to light; capsules are stable for two
                          years [AHFS Drug Information 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Yellow-orange to orange
                          crystalline powder [PDR 1995]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 10, 20, and 40 mg soft gelatin
                          capsules. [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store at 15-30 C (59-86 F). Protect
                          from light. [PDR 1995]
 MANUFACTURERS            Hoffman-La Roche, Incorporated
 REFERENCES               Sass JO, Masgrau E, Saurat JH, Nau H.
                          Metabolism of oral 9-cis-retinoic acid in the
                          human. Identification of
                          9-cis-retinoyl-beta-glucuronide and
                          9-cis-4-oxo-retinoyl-beta-glucuronide as
                          urinary metabolites. Drug Metab Dispos 1995
                          Sep;23(9):887-91.
 REFERENCES               Otley CC, Avram MR, Johnson RA. Isotretinoin
                          treatment of human immunodeficiency
                          virus-associated eosinophilic folliculitis.
                          Results of an open, pilot trial. Arch
                          Dermatol. 1995 Sep;131(9):1047-50.
 REFERENCES               Lewi D, Reboredo G, Jauregui Rueda H,
                          Monticelli A, Losso M, Vujacich C, Litovska
                          S, Marantz A, De la Torre A, Politi P. Phase
                          II trial of 13-cis-retinoic acid (CRA) in
                          AIDS-related Kaposi's sarcoma (KS) (Meeting
                          abstract). Proc Annu Meet Am Assoc Cancer
                          Res;14:A835 1995.
 REFERENCES               Markowska J, Nowak M, Niecewicz R,
                          Breborowicz J, Wiese E, Zengteler G. Results
                          of topical treatment of HPV infection in the
                          uterine cervix using interferon beta,
                          13-cis-retinoic acid and TFX. Eur J Gynaecol
                          Oncol. 1994;15(1):65-9.
 REFERENCES               Birley HD, Luzzi GA, Walker MM, Ryait B,
                          Taylor-Robinson D, Renton AM. The association
                          of human papillomavirus infection with
                          balanopostihitis: a description of five cases
                          with proposals for treatment. Int J STD AIDS.
                          1994 Mar-Apr;5(2):139-41.
 REFERENCES               Digiovanna JJ. Therapy of skin cancer,
                          psoriasis, keratinization disorders, and
                          cystic acne. Crisp Data Base National
                          Institutes of Health.
 REFERENCES               Lippman SM, Hong WK. 13-cis-retinoic acid
                          plus interferon-alpha in solid tumors:
                          keeping the cart behind the horse
                          [editorial]. Ann Oncol. 1994 May;5(5):391-3.
 REFERENCES               Rosenthal E, Pesce A, Vinti H, Reboulot B,
                          Hoffman P, Cassuto JP. Isotretinoin plus
                          interferon alpha-2a in AIDS-related Kaposi's
                          sarcoma. Int Conf AIDS. 1993 Jun
                          6-11;9(1):403 (abstract no. PO-B12-1607).
 REFERENCES               Ampel NM, Stout ML, Garewal HS, Davis JR.
                          Persistent rectal ulcer associated with human
                          papillomavirus type 33 in a patient with
                          AIDS: successful treatment with isotretinoin.
                          Rev Infect Dis. 1990 Nov-Dec;12(6):1004-7.
 REFERENCES               Myskowski PL, Safai B. TREATMENT OF KAPOSI'S
                          SARCOMA. Aids and Infections of Homosexual
                          Men. Second Edition. Ma P and Armstrong D,
                          eds. Boston, Butterworths, p. 355-70 1989.
 ENTRY MONTH              9408
 LAST REVISION DATE       960424
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
