Co-Medication of Statins with Contraindicated Drugs

Background: 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. Objective: This study was performed to describe the co-medication prevalence of CYP3A4-metabolized statins with contraindicated drugs. Methods: 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. Results: 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. Conclusion: 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.