Prevalence of potential drug interactions in Thai patients receiving simvastatin: The causality assessment of musculoskeletal adverse events induced by statin interaction

Drug-drug interactions are one of the major risk factors associated with statin-induced myopathy. Although simvastatin is widely used in Thailand, studies investigating the prevalence of potential simvastatin-drug interactions (SDIs) and its clinical relevance in Thai population are still limited. We aimed to investigate the prevalence of potential SDIs (phase 1 study) and musculoskeletal adverse effects (AEs) associated with those interactions (phase 2 study). A phase 1 study was retrospectively conducted with outpatients at a 60-bed hospital who received simvastatin between July 1, 2012 and June 30, 2013. In phase 2, study was cross-sectionally conducted in outpatients whose prescriptions contain potential SDIs. Musculoskeletal AEs were evaluated by using symptom checklist questionnaires and measuring plasma creatinine kinase (CK). The causal relationship between the AEs and the potential SDIs was assessed using a Drug Interaction Probability Scale.Out of 3447 simvastatin users, potential SDIs were found in 314 patients (9.1%). The prevalence of prescriptions containing potential SDIs was in the range of 4.7-6.0%. Two-thirds of the potential SDIs were rated to be highly significant while more than 70% were in contraindication list. The most common precipitant drugs were gemfibrozil (382 prescriptions), colchicine (171 prescriptions) and amlodipine (152 prescriptions). Of 49 patients recruited into phase 2 study, we found that 31 patients (63.3%) had myopathy. Myalgia was the most frequently identified AEs (n = 18, 58.1%), followed by asymptomatic rising CK (n = 8, 25.8%), and myositis (n = 5, 16.1%). Musculoskeletal AEs associated with SDIs were found in 16 patients (51.6%). Of these, we found 50.0%, 31.3% and 18.8% had asymptomatic rising CK, myalgia, and myositis, respectively. Precipitant drugs associated with myopathy were amlodipine (2 possible cases), colchicine (3 possible cases), gemfibrozil (8 possible and 1 probable cases), nevirapine (1 possible case), and nicotinic acid (1 possible case).Potential SDIs have been found in the Thai population with a prevalence that is consistent with previous reports. Half of the musculoskeletal AEs identified were associated with SDIs. Systematic screening and management with interdisciplinary co-operation are needed to increase awareness of potential SDIs.