E Bondon-Guitton1, S Combret2, M C Pérault-Pochat3, M Stève-Dumont4, H Bagheri5, F Huguet6, F Despas7, A Pathak7, J L Montastruc5. 1. Service de Pharmacologie Médicale et Clinique, Centre Midi-Pyrénées de Pharmacovigilance, Pharmacoépidémiologie et Informations sur le Médicament, Pharmacopôle Midi-Pyrénées, CHU Toulouse, Faculté de Médecine de l'Université de Toulouse, Toulouse, France. emmanuelle.bondon@univ-tlse3.fr. 2. Centre Régional de Pharmacovigilance de Bourgogne, Centre Hospitalier Universitaire, Dijon, France. 3. Pharmacologie Clinique et Vigilances, Centre Hospitalier Universitaire, Poitiers, France. 4. Centre Régional de Pharmacovigilance, Hôpital de Cimiez, Nice, France. 5. Service de Pharmacologie Médicale et Clinique, Centre Midi-Pyrénées de Pharmacovigilance, Pharmacoépidémiologie et Informations sur le Médicament, Pharmacopôle Midi-Pyrénées, CHU Toulouse, Faculté de Médecine de l'Université de Toulouse, Toulouse, France. 6. Service d'Hématologie, Institut Universitaire du Cancer, Toulouse, France. 7. Service de Pharmacologie Médicale et Clinique, CHU Toulouse, Faculté de Médecine de l'Université de Toulouse, Toulouse, France.
Abstract
BACKGROUND: Over the past few years, data have suggested that severe peripheral arterial occlusive disease (PAOD) is associated with nilotinib exposure. However, the characteristics of this adverse drug reaction are poorly described since its frequency is low. As far as we know, no study using a spontaneous adverse drug reactions reporting system was performed to describe the characteristics of cases of PAOD related to nilotinib. OBJECTIVE: We performed a study to describe the cardiovascular risk profile of cases of PAOD in patients treated with nilotinib spontaneously reported to the French Pharmacovigilance Database (FPVD). PATIENTS/ METHODS: We selected all cases of "vascular disorders," as the System Organ Class in MedDRA®, in which nilotinib was "suspected" and recorded in the French Pharmacovigilance Database between 2007 and 21 October 2014. We then identified cases of PAOD with a Low Level Term and through a detailed summary of the clinical description. RESULTS: We identified 25 cases of POAD. Most of the patients were older than 60 years (84 %) or had another cardiovascular risk factor such as hypercholesterolemia, arterial hypertension, overweight/obesity, smoking, or diabetes mellitus (72 %). Females (13 cases) and males (12 cases) were equally represented, but the presence of cardiovascular risk factors was more frequent in females than in males. The mean time from initiation of nilotinib to PAOD onset was 24 months and was significantly longer in patients aged less than 60 years compared with those aged over 60 years (33.8 ± 24.6 months vs. 22.6 ± 17.5 months, p = 0.002). Pre-existing cardiovascular risk factors, especially diabetes mellitus, also seem to accelerate its occurrence. CONCLUSIONS: The FPVD is a useful tool in describing the cardiovascular risk profile of patients with PAOD during nilotinib exposure. Physicians have to be particularly vigilant in patients older than 60 years of age; in patients younger than 60 years of age, long-term surveillance has to be maintained.
BACKGROUND: Over the past few years, data have suggested that severe peripheral arterial occlusive disease (PAOD) is associated with nilotinib exposure. However, the characteristics of this adverse drug reaction are poorly described since its frequency is low. As far as we know, no study using a spontaneous adverse drug reactions reporting system was performed to describe the characteristics of cases of PAOD related to nilotinib. OBJECTIVE: We performed a study to describe the cardiovascular risk profile of cases of PAOD in patients treated with nilotinib spontaneously reported to the French Pharmacovigilance Database (FPVD). PATIENTS/ METHODS: We selected all cases of "vascular disorders," as the System Organ Class in MedDRA®, in which nilotinib was "suspected" and recorded in the French Pharmacovigilance Database between 2007 and 21 October 2014. We then identified cases of PAOD with a Low Level Term and through a detailed summary of the clinical description. RESULTS: We identified 25 cases of POAD. Most of the patients were older than 60 years (84 %) or had another cardiovascular risk factor such as hypercholesterolemia, arterial hypertension, overweight/obesity, smoking, or diabetes mellitus (72 %). Females (13 cases) and males (12 cases) were equally represented, but the presence of cardiovascular risk factors was more frequent in females than in males. The mean time from initiation of nilotinib to PAOD onset was 24 months and was significantly longer in patients aged less than 60 years compared with those aged over 60 years (33.8 ± 24.6 months vs. 22.6 ± 17.5 months, p = 0.002). Pre-existing cardiovascular risk factors, especially diabetes mellitus, also seem to accelerate its occurrence. CONCLUSIONS: The FPVD is a useful tool in describing the cardiovascular risk profile of patients with PAOD during nilotinib exposure. Physicians have to be particularly vigilant in patients older than 60 years of age; in patients younger than 60 years of age, long-term surveillance has to be maintained.
Authors: Karl J Aichberger; Susanne Herndlhofer; Gerit-Holger Schernthaner; Martin Schillinger; Gerlinde Mitterbauer-Hohendanner; Christian Sillaber; Peter Valent Journal: Am J Hematol Date: 2011-04-27 Impact factor: 10.047
Authors: T D Kim; D Rea; M Schwarz; P Grille; F E Nicolini; G Rosti; L Levato; F J Giles; H Dombret; T Mirault; H Labussière; R Lindhorst; W Haverkamp; I Buschmann; B Dörken; P D le Coutre Journal: Leukemia Date: 2013-03-05 Impact factor: 11.528
Authors: F J Giles; M J Mauro; F Hong; C-E Ortmann; C McNeill; R C Woodman; A Hochhaus; P D le Coutre; G Saglio Journal: Leukemia Date: 2013-03-05 Impact factor: 11.528
Authors: Jeanne Hersant; Martine Gardembas; Georges Leftheriotis; Patrick Vandeputte; Pierre Abraham; Samir Henni Journal: Leuk Res Rep Date: 2019-05-25