Turning a blind eye to deferasirox's toxicity?

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 contraindicated or inadequate in patients with non-transfusion-dependent thalassaemias" in addition to transfused thalassaemia patients.1Pocock N CHMP recommends extension of therapeutic indications for deferasirox (Exjade®).http://www.nelm.nhs.uk/en/NeLM-Area/News/2012---November/19/CHMP-recommends-extension-of-therapeutic-indications-for-deferasirox-Exjade-/Google Scholar The recommendation coincided with the release of a report of 4113 deaths in patients treated with deferasirox.2AnonExjade side effects in real world: a study of 17,764 patients.http://www.ehealthme.com/q/exjade-side-effects-drug-interactionsGoogle Scholar Previously, 11·7% 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.3Pocock N CHMP finalises review of deaths associated with deferasirox (Exjade®) in the US and updates to the SPC.http://www.nelm.nhs.uk/en/NeLM-Area/News/2009---November/02/CHMP-finalises-review-of-deaths-associated-with-deferasirox-Exjade-in-the-US-and-updates-to-the-SPC-/Google Scholar It was also suggested that most of the reported deaths occurred in elderly patients with underlying myelodysplastic syndromes.3Pocock N CHMP finalises review of deaths associated with deferasirox (Exjade®) in the US and updates to the SPC.http://www.nelm.nhs.uk/en/NeLM-Area/News/2009---November/02/CHMP-finalises-review-of-deaths-associated-with-deferasirox-Exjade-in-the-US-and-updates-to-the-SPC-/Google Scholar 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.4AnonList of reactions reported by people who where taking Exjade: 2474 reported reactions.http://www.fda-reports.com/exjade/reaction/death/page1.htmlGoogle Scholar 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.4AnonList of reactions reported by people who where taking Exjade: 2474 reported reactions.http://www.fda-reports.com/exjade/reaction/death/page1.htmlGoogle Scholar Information on the deaths was limited and non-specific, with about an additional 300 cases generally characterised as patients with iron overload.4AnonList of reactions reported by people who where taking Exjade: 2474 reported reactions.http://www.fda-reports.com/exjade/reaction/death/page1.htmlGoogle Scholar 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.4AnonList of reactions reported by people who where taking Exjade: 2474 reported reactions.http://www.fda-reports.com/exjade/reaction/death/page1.htmlGoogle Scholar 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.2AnonExjade side effects in real world: a study of 17,764 patients.http://www.ehealthme.com/q/exjade-side-effects-drug-interactionsGoogle Scholar, 4AnonList of reactions reported by people who where taking Exjade: 2474 reported reactions.http://www.fda-reports.com/exjade/reaction/death/page1.htmlGoogle Scholar, 5Kontoghiorghes GJ Kolnagou A Peng CT Shah SV Aessopos A Safety issues of iron chelation therapy in patients with normal range iron stores including thalassaemia, neurodegenerative, renal and infectious diseases.Expert Opin Drug Saf. 2010; 9: 201-206Crossref PubMed Scopus (50) Google Scholar Similarly, the reporting in the medical literature of mortality and morbidity including renal, hepatic, and bone-marrow failures during treatment with deferasirox is absent.5Kontoghiorghes GJ Kolnagou A Peng CT Shah SV Aessopos A Safety issues of iron chelation therapy in patients with normal range iron stores including thalassaemia, neurodegenerative, renal and infectious diseases.Expert Opin Drug Saf. 2010; 9: 201-206Crossref PubMed Scopus (50) Google Scholar 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.2AnonExjade side effects in real world: a study of 17,764 patients.http://www.ehealthme.com/q/exjade-side-effects-drug-interactionsGoogle Scholar, 4AnonList of reactions reported by people who where taking Exjade: 2474 reported reactions.http://www.fda-reports.com/exjade/reaction/death/page1.htmlGoogle Scholar, 5Kontoghiorghes GJ Kolnagou A Peng CT Shah SV Aessopos A Safety issues of iron chelation therapy in patients with normal range iron stores including thalassaemia, neurodegenerative, renal and infectious diseases.Expert Opin Drug Saf. 2010; 9: 201-206Crossref PubMed Scopus (50) Google Scholar I declare that I have no conflicts of interest. Deferasirox's toxicityG J Kontoghiorghes' Correspondence (April 6, p 1183)1 contains substantial factual inaccuracies about deferasirox and selective omission of important information. We wish to correct these inaccuracies and to provide more complete information for doctors and their patients. Full-Text PDF