Turning a blind eye to deferasirox's toxicity?

摘要

The European Commission is considering a recommendation by the European Medicines Agency (EMA) to approve the use of deferasirox "in the treatment of chronic iron overload requiring chelation therapy when deferoxamine therapy is contra-indicated or inadequate in patients with non-transfusion-dependent thalassaemias" in addition to transfused thalassaemia patients.The recommendation coincided with the release of a report of 4113 deaths in patients treated with deferasirox.2 Previously, 117% mortality (1935 of 16 514 patients) was reported by the EMA and a warning was issued that deferasirox's toxicity is likely to increase when the maximum recommended dose increases from 30 to 40 mg/kg per day.3 It was also suggested that most of the reported deaths occurred in elderly patients with underlying myelodysplastic syndromes.3 However, a report of individual deaths has revealed that there was indiscriminate and uncontrolled use of deferasirox in many patients of various ages, including many young individuals.4 Of the categories of patients affected from a total of 2474 deaths, there were about 700 with myelodysplastic syndromes, 87 with sickle-cell disease, 77 with haemochromatosis, and ten with thalassaemia.4 Information on the deaths was limited and nonspecific, with about an additional 300 cases generally characterised as patients with iron overload.4 About 500 of the cases seem not to have been related to transfusional iron overload but included patients with cancer, cardiovascular disease, and neurological disorders, and other patients with normal iron stores.4 The death rate and indiscriminate use of deferasirox is alarming with regard to the safety for all patients involved, especially since no sufficient or effective safeguards seem to have been implemented so far to reduce toxicity.2A5 Similarly, the reporting in the medical literature of mortality and morbidity including renal, hepatic, and bone-marrow failures during treatment with deferasirox is absent.5 This raises major concerns about the role and practices of the pharmaceutical companies, regulatory authorities, physicians, and others involved in drug safety and the protection of patients' interests.The toxicity and efficacy issues during the development of the generic chelating drugs deferiprone and deferoxamine were more vigorously discussed in the medical literature and were also more transparent than were those for deferasirox. Subsequently, the mortality and morbidity incidence was widely reported and prophylactic measures were taken, which resulted in much lower toxicity outcomes than those reported for deferasirox.