title: The contribution of pharmacogenetics to pharmacovigilance.
abstract: Since the beginning of this century, information on pharmacogenetics appears in the summary of product characteristics (SPC) of drugs. Pharmacogenetic tests particularly concern the enzymes involved in the metabolism of drugs, among which P450 cytochromes. Some patients known as poor metabolisers eliminate some drugs more slowly, causing overdoses and adverse drug reactions (ADRs). The best-known examples are AVK and VKORC1-CYP2C9 or clopidogrel and CYP2C19. In the USA, the tests are recommended before the introduction of these drugs to prevent the occurrence of ADRs. Other tests are also commonly performed to address the toxicity of certain anticancer drugs (DPYD-capecitabine, UGT1A1-irinotecan, TPMT 6-mercaptopurine). Pharmacogenetic testing is also available to identify HLA loci that are very strongly associated with the occurrence of immuno-allergic reactions to a specific drug. The best-known example is HLA-B*5701, strongly associated with hypersensitivity to abacavir, and this test is now always prescribed before the instatement of this drug.
authors.affiliation: Service de pharmacologie médicale et clinique, centre Midi-Pyrénées de pharmacovigilance, pharmacoépidémiologie et informations sur le médicament, pharmacopôle Midi-Pyrénées, faculté de médecine, université de Toulouse, CHU, 37, allées Jules-Guesde, 31000 Toulouse, France. Electronic address: emmanuelle.bondon@univ-tlse3.fr.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Bondon-Guitton
authors.affiliation: Service de pharmacologie médicale et clinique, faculté de médecine, université de Toulouse, CHU de Toulouse, 37, allées Jules-Guesde, 31000 Toulouse, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Despas
authors.affiliation: CEA DSV/iMETI, division d'immunovirologie, IDMIT, département de pharmacologie, centre d'immunologie des infections virales et des maladies auto-immunes, hôpital Bicêtre, faculté de médecine, université Paris Sud, Assistance publique-Hôpitaux de Paris, 94270 Le Kremlin-Bicêtre, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Becquemont
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D015224:Dideoxynucleosides / Q000009:adverse effects / Q000276:immunology; D004342:Drug Hypersensitivity / Q000235:genetics / Q000276:immunology; D062787:Drug Overdose / Q000453:epidemiology / Q000235:genetics; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods*; D060735:Pharmacovigilance; D000099227:Abacavir
chemical_list: D000970:Antineoplastic Agents; D003577:Cytochrome P-450 Enzyme System; D015224:Dideoxynucleosides; D000099227:Abacavir
keywords: Adverse drug reactions; CYP2C19; CYP2D6; DPYD; HLA; Pharmacogenetics; Pharmacovigilance; TPMT; UGT1A1; VKORC1/CYP2C9