Effect of Concomitant Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) on the Pharmacokinetics of Atorvastatin

BACKGROUND AND OBJECTIVE: Icosapent ethyl is a high-purity prescription form of eicosapentaenoic acid ethyl ester approved as an adjunct to diet to reduce triglyceride levels in adult patients with triglyceride levels ≥500 mg/dL (≥5.65 mmol/L). The objective of this open-label, drug–drug interaction study was to examine the effects of icosapent ethyl on the steady-state pharmacokinetics of atorvastatin, a commonly prescribed medication in patients with dyslipidaemia. METHODS: Thirty healthy subjects received atorvastatin 80 mg/day on days 1–7, icosapent ethyl 4 g/day on days 8–28, and co-administration on days 29–35. Primary end-points were natural log-transformed maximum plasma concentration (C (max)) and area under the concentration-versus-time curve from 0 to 24 h (AUC(0–24)) for atorvastatin, 2-hydroxyatorvastatin, and 4-hydroxyatorvastatin with and without icosapent ethyl. RESULTS: Of the 30 subjects enrolled, 26 completed the study. The 90 % confidence intervals for C (max) and AUC(0–24) least-squares geometric mean ratios were within the 0.80–1.25 bounds. Concomitant administration of icosapent ethyl and atorvastatin was safe and well tolerated and icosapent ethyl did not significantly change the steady state C (max) and AUC(0–24) of atorvastatin, 2-hydroxyatorvastatin, or 4-hydroxyatorvastatin. CONCLUSIONS: At steady-state concentrations, icosapent ethyl did not have an effect on the pharmacokinetics of atorvastatin. Co-administration of icosapent ethyl and atorvastatin was safe and well tolerated in healthy adult subjects.