Abstract

BackgroundThe 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.ObjectiveThis study was performed to describe the co-medication prevalence of CYP3A4-metabolized statins with contraindicated drugs.MethodsThe 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.ResultsA 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.ConclusionThe 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.

Highlights

  • Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors are considered to be the first-choice drug for patients with dyslipidemia to lower their cholesterol levels

  • A total of 2,119,401 patients received cytochrome P450 3A4 (CYP3A4)-metabolized statins and 60,254 (2.84%) patients were co-medicated with contraindicated drugs

  • The proportion of co-medication of statins with contraindicated drugs was relatively lower than that of previous studies; the co-medication occurring by different medical institutions was not managed appropriately

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Summary

Introduction

Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) are considered to be the first-choice drug for patients with dyslipidemia to lower their cholesterol levels. Several studies have reported the effects of statins on primary and secondary prevention of cardiovascular events and mortality [1,2,3,4,5,6]. Statins are generally considered to be well tolerated and to have a good safety profile, statin-induced myopathy including rhabdomyolysis has been reported [7]. Drug-drug interaction (DDI) is considered to be a risk factor for this adverse effect of statins [8]. Previous studies support the importance of DDI among statin users. Data from spontaneous adverse event reports indicated that approximately 50% of rhabdomyolysis cases among statin users are associated with DDIs [9].

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