African Journal of Pharmacy and Pharmacology Vol. 6(8), pp. 525-529, 29 February, 2012 Available online at http://www.academicjournals.org/AJPP DOI: 10.5897/AJPP11.677 ISSN 1996-0816 © 2012 Academic Journals Full Length Research Paper Safety aspects of chronic myeloid leukemia pharmacotherapy Alexandra Savova, Assena Stoimenova*, Manoela Manova and Guenka Petrova Department of Social Pharmacy and Pharmacoeconomics, Faculty of Pharmacy, Medical University, Sofia, Bulgaria. Accepted 15 February, 2012 Chronic myeloid leukaemia (CML) is a clonal myeloproliferative disorder of pluripotent stem cells, first described by John Hughes Bennett in 1845. Previously, the treatment options, such as hydroxicarbamide, interferon, busulfan and radiotherapy, only controlled the disease while the novel therapeutic options increased significantly the rate of remissions. Untreated patients in chronic phase (CML-CP) inevitably progressed to CML-BC (blast crisis), an aggressive form of acute leukaemia. Treatment with imatinib mesylate was associated with high response rate and an improved overall survival rate, especially when used in chronic phase. Options for patients resistant to imatinib include either dose increase or use of dasatinib or nilotinib. The objective of the current study was to analyse the impact of the severity and frequency of the adverse drug reactions on treatment results and to determine the treatment costs with imatinib, dasatinib, and nilotinib. An epidemiology and safety model based on information about the registered patients with CML in Bulgaria was established. Treatment costs for each therapy option and the treatment costs of adverse drug reactions (ADR) were determined for 6 months, and 1 year time horizons, from the payer’s perspective. The results confirmed that the frequency and severity of ADRs influenced the total pharmacotherapy costs. Nilotinib is the preferred therapeutic and economic alternative. Key words: Chronic myeloid leukaemia, adverse drug reactions, nilotinib, dasatinib, imatinib. INTRODUCTION Chronic myeloid leukaemia (CML) is a clonal myeloproliferative disorder of a pluripotent stem cell first described by John Hughes Bennett in 1845. The annual incidence of CML is 1.6 cases per 100,000 adults. According to the European Orphan Drug Regulation, 141/2000 CML is classified as a rare diseases (incidence below 1 case per 2 000 adults) (Quintas-Cardama, 2006; Regulation EC, 1999). CML was the first malignancy that had a specific chromosomal abnormality uniquely linked to it after the discovery of the Philadelphia (Ph) chromosome. Three phases of disease progression are recognized in CML: Chronic phase (CP), accelerated phase (AP), and blast crisis (BC). Each of the three clinical phases of CML is more resistant to treatment than *Corresponding author. E-mail: assena_stoimenova@mail.bg. Tel: +359887749665. Fax: +35929879874. previous phase (Moellman-Coelho et al., 2010). After a median of 3 to 5 years, untreated patients with CML-CP inevitably progressed to CML-BC, which is a form of acute leukaemia, sometimes refractory to chemotherapy, associated with high poor survival (Besa et al., 2011). The research and development of new drugs for the treatment of CML continues and opportunities are constantly looked to improve the care for people with CML (Tao et al., 2011; Xie et al., 2011). Previously, the treatment options, like hydroxicarbamide, interferon, busulfan and radiotherapy, only controlled the disease, while the newly authorised medicinal products significantly increased the rates of remission. The introduction of tyrosine kinase inhibitors (TKI) as a standard treatment of CML was associated with both high response rates and improved overall survival, especially when used in CP, and imatinib was the first of a kind (Baccarani et al., 2006; Kantarjian et al., 2007a). However, CML patients sometimes become resistant or