Statin medication in patients treated with antiepileptic drugs in Norway

Abstract

Purpose: The lipid-lowering response of statins metabolized by cytochrome P450 3A4 (CYP3A4) has previously been shown to be diminished by concurrent use of enzyme-inducing antiepileptic drugs (EIAEDs). The aim of this study was to compare statin prescription in patients receiving EIAEDs versus non-enzyme-inducing antiepileptic drugs (NEIAEDs), before and after introduction of prescribing restrictions for statins in Norway.

Methods: The Norwegian Prescription Database was used to extract data on patients using antiepileptic drugs and statins during 2004 and 2008. Statin type and dose used were compared between patients treated with at least one EIAED (i.e., carbamazepine, phenobarbital, phenytoin, primidone) and those receiving NEIAEDs only (i.e., all other antiepileptic drugs).

Results: The number of included patients co-medicated with statins and AEDs was 4855 in 2004 and 9880 in 2008. Among these patients, 2827 and 3160, respectively, were treated with EIAEDs. The CYP3A4 statins (i.e., simvastatin, atorvastatin and lovastatin) accounted for 85% of all statins in 2004, increasing to 93% in 2008. There was no significant difference in the likelihood of being prescribed a CYP3A4 statin versus a non-CYP3A4 statin among patients receiving EIAEDs and NEIAEDs. The average daily dose of individual CYP3A4 statins was not different between the AED groups.

Conclusions: The present study shows that the interaction risk between CYP3A4-metabolized statins and EIAEDs is largely overlooked in Norwegian clinical practice. To avoid therapeutic failure of statin treatment in patients using AEDs, implementation of strategies for systematic management of drug interactions is warranted.