      Document 0029
 DOCN  DRG0029
 UNIQUE IDENTIFIER        DRG-0218
 NAME OF SUBSTANCE        Acitretin [USAN 1996]
 REGISTRY NUMBER          55079-83-9
 STANDARD CHEMICAL NAME   (all-E)-9-(-Methoxy-2,3,6-trimethylphenyl)-
                          3,7-dimethyl-2,4,6,8-nonatetraenoic acid
                          [Merck Index 1989]
 SYNONYMS                 Soriatane [USAN 1996]
 SYNONYMS                 Neotigason [Merck Index 1989]
 SYNONYMS                 Etretin [Merck Index 1989]
 PROTOCOL ID NUMBERS      Open FDA 239A
 SECONDARY SOURCE ID      Ro 10-1670 [Merck Index 1989]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Certain retinoids have been
                          shown in rats and mice to induce hepatic
                          cytochrome P-50 enzyme. Acitretin, the active
                          primary metabolite of etretinate (another
                          retinoid used in treatment of psoriasis) may
                          induce its own metabolism. Acitretin is
                          eliminated far more rapidly from the human
                          body than is etretinate. Re-esterification
                          (in the body) of acitretin to etretinate
                          results in a loss of the metabolic advantage
                          of the former. Retinoids (including
                          acitretin) contribute potentially to cancer
                          chemotherapy and chemoprevention. They induce
                          cell differentiation, inhibit cell
                          proliferation, suppress expression of viral
                          oncogenesis, and inhibit angiogenesis
                          necessary for tumor growth. [J Pharm Sci 1994
                          May;83(5)] [J Am Acad Dermatol 1992 Dec;27(6
                          pt 2)] [J Cell Biochem 1994 Dec;56(4)]
 DISEASES STUDIED/TREATED Treatment of psoriasis in HIV-positive
                          patients [FDA 239A]
 CLASSIFICATION CODE      Antipsoriatic [USAN 1996]
 OTHER MAJOR USES         Various dermatoses [Dermatologica
                          1988;176(4)]
 ADVERSE EFFECTS          Adverse reactions are dose-related and
                          typical of hypervitaminosis A. They include
                          alopecia, cheilitis and drying of the mucous
                          membranes, hypertriglyceridemia, and
                          elevation of cholesterol levels. Acitretin
                          has teratogenic potential. It appears to be
                          connected to higher occurrence of
                          vulvo-vaginal candidiasis. Extensive
                          extraspinal hyperostosis after long-term oral
                          retinoid (acitretin) therapy was noted in one
                          patient. [Drugs 1992 Apr;43(4)] [J Clin
                          Epidemiol 1995 Aug;48(8)] [J Am Acad Dermatol
                          1995 Feb;32(2 pt 2)]
 CONTRAINDICATIONS        Contraindicated in women of childbearing
                          potential because of teratogenicity. [FDA
                          239A]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Synthetic retinoid; free
                          acid form and major metabolite of etretinate
                          [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C21H26O3 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 326.44 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 228-230 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMP: C77.27%, H8.03%, O14.70%
                          [Merck Index 1989]
 SUBSTANCE DELIVERY DATA  Oral. [FDA 239A]
 MANUFACTURERS            Hoffmann-La Roche, Incorporated
 REFERENCES               Blum A, Scherwitz C, Rassner G.
                          Pseudoallergic hepatitis after a single
                          intake of 10 mg acitretin (Neotigason) for
                          treatment of psoriasis pustulosa [letter].
                          Acta Derm Venereol 1995 Jul;75(4):332.
 REFERENCES               Lambert WE, Meyer E, De Leenheer AP, De
                          Bersaques J, Kint AH. Pharmacokinetics of
                          acitretin. Acta Derm Venereol Suppl. (Stockh)
                          1994:186:122-3.
 REFERENCES               Larsen FG. Pharmacokinetics of etretinate and
                          acitretin with special reference to treatment
                          of psoriasis. Acta Derm Venereol Suppl
                          (Stockh) 1994;190:1-33.
 REFERENCES               Kullavanijaya P, Kulthanan K. Clinical
                          efficacy and side effects of acitretin on the
                          disorders of keratinization: a one-year
                          study. J Dermatol 1993 Aug;20(8):501-6.
 REFERENCES               Surber C, Wilhelm KP, Bermann D, Maibach HI.
                          In vivo skin penetration of acitretin in
                          volunteers using three sampling techniques.
                          Pharm Res 1993 Sep;10(9):1291-4.
 REFERENCES               Bouscarat F, Picard C, Bouvet E, Grossin M,
                          Crickx B, Belaich S. Lichen planus in HIV
                          infection. Intl Conf AIDS. 1993 Jun
                          6-11;9(1):449 (abstract no. PO-B20-1883).
 REFERENCES               Meyer E, de Bersaques J, Lambert WE, de
                          Leenheer AP, Kint AH. Skin, adipose tissue
                          and plasma levels of acitretin with rare
                          occurrence of esterified acitretin during
                          long-term treatment. Acta Derm Venereol 1993
                          Apr;73(2):113-5.
 REFERENCES               Mork NJ, Kolbenstvedt A, Austad J. Efficacy
                          and skeletal  side effects of two years'
                          acitretin treatment. Acta Derm Venereol
                          (Stockh) 1992 Nov;72(6):445-8.
 REFERENCES               Kingston TP, Matt LH, Lowe NJ. Etretin
                          therapy for severe psoriasis. Evaluation of
                          initial clinical responses. Arch Dermatol
                          1987 Jan;123(1):55-8.
 ENTRY MONTH              9411
 LAST REVISION DATE       960424
 

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