title: Preventable and potentially preventable serious adverse reactions induced by oral protein kinase inhibitors through a database of adverse drug reaction reports.
abstract: Antineoplastic drugs are one of the pharmacological classes more frequently involved in occurrence of "serious" adverse drug reactions. However, few epidemiological data are available regarding the preventability of adverse drug reactions with ambulatory cancer chemotherapy. We assessed the rate and characteristics of "preventable" or "potentially preventable" "serious" adverse drug reactions induced by oral protein kinase inhibitors (PKIs). We performed a retrospective study with all "serious" adverse drug reactions (ADRs) recorded from 1 January 2008 to 31 December 2009 in the French Pharmacovigilance Database with the eight oral protein kinase inhibitors marketed in France: sorafenib, imatinib, erlotinib, sunitinib, dasatinib, lapatinib, nilotinib and everolimus (Afinitor®) using the French adverse drug reactions preventability scale. This study was carried out on 265 spontaneous notifications. Most of adverse drug reactions were "unpreventable" (63.8 %). Around one third were "unevaluable" due to notifications poorly documented (medical history, dosage, use of drugs as first or second intention, concomitant drugs). One (0.4 %) adverse drug reaction was "preventable" with dasatinib (subdural hematoma) and three (1.1 %) were "potentially preventable" (hepatic adverse drug reactions): two with imatinib and one with sorafenib. For these four cases, we identified some characteristics: incorrect dosages, drug interactions and off-label uses. An appropriate prescription could avoid the occurrence of 1.5 % "serious" adverse drug reactions with oral PKIs. This rate is low and further studies are needed to compare our results by using other preventability instruments and to improve the French ADRs Preventability Scale.
authors: Laboratoire de Pharmacologie Médicale et Clinique, Equipe de Pharmaco Epidémiologie INSERM U 1027, Faculté de Médecine de l'Université de Toulouse and Service de Pharmacologie Clinique, Centre Midi-Pyrénées de Pharmaco Vigilance, de Pharmaco Epidémiologie et d'Informations sur le Médicament, Centre Hospitalier Universitaire, Toulouse, France.
authors: Adeline
authors: A
authors: Egron
authors: Pascale
authors: P
authors: Olivier-Abbal
authors: Aurore
authors: A
authors: Gouraud
authors: Samy
authors: S
authors: Babai
authors: Sandrine
authors: S
authors: Combret
authors: Jean-Louis
authors: JL
authors: Montastruc
authors: Emmanuelle
authors: E
authors: Bondon-Guitton
mesh_terms: D000284:Administration, Oral; D016907:Adverse Drug Reaction Reporting Systems; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016208:Databases, Factual; D054796:Drug Dosage Calculations; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology / Q000517:prevention & control*; D005602:France; D006801:Humans; D008508:Medication Errors / Q000517:prevention & control*; D056687:Off-Label Use; D060735:Pharmacovigilance; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors