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TOX LESSONS LEARNED: FOUR DECADES FDA DERMATOLOGY DRUGS WITHDRAWN

TOX LESSONS LEARNED: FOUR DECADES FDA DERMATOLOGY DRUGS WITHDRAWN. HOWARD I. MAIBACH, M.D. PROFESSOR DEPARTMENT OF DERMATOLOGY UNIVERSITY OF CALIFORNIA SAN FRANCISCO, CALIFORNIA 94143 – 0989. BIG PICTURE. • COMPLEXITY ! • INCONSISTENCY • SCIENCE IMPROVING

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TOX LESSONS LEARNED: FOUR DECADES FDA DERMATOLOGY DRUGS WITHDRAWN

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  1. TOX LESSONS LEARNED: FOUR DECADES FDA DERMATOLOGY DRUGS WITHDRAWN HOWARD I. MAIBACH, M.D. PROFESSOR DEPARTMENT OF DERMATOLOGY UNIVERSITY OF CALIFORNIA SAN FRANCISCO, CALIFORNIA 94143 – 0989

  2. BIG PICTURE • COMPLEXITY ! • INCONSISTENCY • SCIENCE IMPROVING • CANCER : - ASSAYvsDISEASE

  3. DISCLAIMER NEITHER SUPPORT NOR DENY THESE REGULATORY JUDGEMENTS

  4. THEORY • PERCIVAL POTTS & SCROTUM - SCROTUM – HIGHLY PERMEABLE • SKIN PAINTING ASSAYS – 100 YRS • HUMAN SKIN TUMORS – OBVIOUS • INTERNAL ORGANS? - BLADDER ? (DYES) - BLOOD ? (BENZENE)

  5. WITHDRAWALS 1) BITHIONOL – 1967 PHOTOACD 2) HALOGENATED SALICYLANILIDES – 1975 PHOTOACD 3) *CHLOROFORM – 1976 CANCER 1976 – NCI – ORAL HEPATIC & RENAL 4) AZARIBINE – 1976 THROMBOEMBOLISM

  6. WITHDRAWALS – con’t. 5) ZIRCONIUM – 1976 GRANULOMA *K ARSENITE 1980 CANCER J. HUTCHINSON (100 YRS.) BENOXAPROFEN 1982 RENAL & HEPATIC 8) CHLORHEXIDINE 1984 BURNS

  7. WITHDRAWALS – con’t. 9) TEMAFLOXACIN – 1992 RENAL & HEPATIC 10) ASTEMIZOLE – 1999 DRUG - DRUG INTERACTION 11) TERFENADINE – 1997 DRUG - DRUG INTERACTION 12) ETRETINATE – 2002 TERATOGENIC

  8. WITHDRAWALS – con’t. EFALIZUMAB – 2009 PML (PROGRESSIVE MULTIFOCAL LUEKOENCEPHALOPATHY)  CANCER: 2/13

  9. BLACK BOX • METHOTREXATE LYMPHOMA • TACROLIMUS LYMPHOMA • PIMECROLIMUS CLINICALRELEVANCE – SUBJUDICE

  10. “PACKAGE INSERT LABEL” PHOTOCARCINOGENICITY - RETINOIC ACID - BENZOYL PEROXIDE CLINICALRELEVANCE: SUBJUDICE

  11. DERMATOLOGIC DRUGS ORAL / PARENTERAL ~ HALF – ANIMAL ASSAY + CLINICALRELEVANCE: SUBJUDICE

  12. CONCLUSIONS SIGNIFICANT PROGRESS: - PHOTOIRRITATION - ALLERGIC CONTACT DERMATITIS - PHOTOALLERGIC CONTACT DERMATITIS - DRUG - DRUG INTERACTION - CLINICAL TRIAL DESIGN MUCH REMAIN TO BE UNDERSTOOD: - CLINICAL RELEVANCE OF CARCINOGENICITY ASSAY

  13. WEAK LINKS • PHARMACOVIGILENCE • COSMETIC VIGILENCE • CONSUMER PRODUCT VIGILENCE

  14. POWER • IARC ! • NEW COMPUTER DATA BASES • FUTURE - BRIGHT ! - SKIN – BIOMARKER

  15. REFERENCE M. MARTIN & H. MAIBACH: DERMATOLOGIC DRUGS WITHDRAWN BY THE FDA FOR SAFETY REASONS MARZULLI & MAIBACH: DERMATOTOXICOLOGY,8THED, INFORMA, 2012, p. 500-509

  16. HOWARD I. MAIBACH, MD TELEPHONE: (415) 673 - 9693 0700 – 0800 Hour SAN FRANCISCO TIME MaibachH@derm.ucsf.edu

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