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.

Mesure de l’évitabilité des effets indésirables médicamenteux en France : état des lieux en 2015

“…Enfin, l'étude ciblée sur la classe des inhibiteurs des protéine-kinases (IPK), réalisée dans la base nationale de pharmacovigilance (BNPV), a montré l'évitabilité la plus faible (1,5 %) [26]. Au-delà des différences (populations, méthodes d'évaluation, types de recueil), les deux…”

“…Dans les études françaises citées ci-dessus, les causes et situations pouvant expliquer la survenue des EIM évitables ont été des erreurs de prescription [16,18,[20][21]25], la non prise en compte d'une allergie [16,18,20,22], des erreurs liées au patient (observance, automédication, oubli ) [16,[20][21]25,27] ou encore des erreurs ou non-respect de dose ou posologie [14][15][19][20][21][22]26]. Un des principaux atouts de ces études, une fois terminées, reste la possibilité de mettre en place des actions correctives, soit sous forme de formation/information des acteurs, soit sous forme d'échanges réguliers entre cliniciens et pharmacologues -surtout lorsque l'étude a eu lieu au niveau local -afin de discuter des facteurs de risques mis en évidence et des améliorations envisageables en pratique.…”

Measuring the preventability of adverse drug reactions in France: A 2015 overview

“…Finally, a study targeting the protein-kinase inhibitor class of drugs performed in the French national pharmacovigilance database reported the lowest figure for preventability (1.5%) [26]. Beyond the differences between the two studies (population, assessment methods, type of data collection) these two very contrasted results can be explained by the fact that elderly populations are particularly sensitive to ADRs, for pharmacokinetic and physiological reasons, because of poly-medication, etc.…”

“…Some twenty studies analysed this issue between the 1980s and 2015. Table 1 gives details of most of these studies, their type (type of study, place and period of data collection, national or other), the medications assessed, the numbers of patients included, the proportions of preventable ADRs in relation to the number of patients or admissions, and the global preventability of the ADRs [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27].Through the years, the methods implemented have become more and more "explicit", enabling a better classification of ADRs into several preventability categories, and normally speaking more reliable than the "implicit" methods based on the opinion of one or several experts. As seen above, this point was not in fact borne out in the review conducted by Hakkarainen et al [9].…”

“…The five most recently published studies use the French method, or an adaptation thereof [23][24][25][26][27]. These studies explore ADR preventability in different environments -hospital wards or…”