Co-medication of statins with contraindicated drugs

The concomitant use of cytochrome P450 3A4 (CYP3A4) metabolized statins (simvastatin, lovastatin, and atorvastatin) with CYP3A4 inhibitors has been shown to increase the rate of adverse events. This study was performed to describe the co-medication prevalence of CYP3A4-metabolized statins with contraindicated drugs. The patients aged 40 or older receiving CYP3A4-metabolized statin prescriptions in 2009 were identified using the national patient sample from a Korea Health Insurance Review and Assessment Service database. Contraindicated co-medication was defined as prescription periods of statins and contraindicated drugs overlapping by at least one day. Co-medication patterns were classified into 3 categories as follows: co-medication in the same prescription, co-medication by the same medical institution, and co-medication by different medical institutions. The proportion of co-medication was analyzed by age, gender, co-morbidities, and the statin's generic name. A total of 2,119,401 patients received CYP3A4-metabolized statins and 60,254 (2.84%) patients were co-medicated with contraindicated drugs. The proportion of co-medication was 4.6%, 2.2%, and 1.8% in simvastatin, lovastatin, and atorvastatin users, respectively. The most frequent combination was atorvastatin-itraconazole, followed by simvastatin-clarithromycin and simvastatin-itraconazole. Among the co-medicated patients, 85.3% were prescribed two drugs by different medical institutions. The proportion of co-medication of statins with contraindicated drugs was relatively lower than that of previous studies; however, the co-medication occurring by different medical institutions was not managed appropriately. There is a need to develop an effective system and to conduct outcomes research confirming the association between co-medication and the risk of unfavorable clinical outcomes.