Journal
JOURNAL OF CLINICAL LIPIDOLOGY
Volume 2, Issue 6, Pages 453-463Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacl.2008.10.007
Keywords
Adverse effects; Cardiovascular diseases; CYP3A4 protein; Cytochrome P450 enzyme system; Drug interactions; Hydroxymethylglutaryl-CoA reductase inhibitors; Human; Hyperlipidemia; Polypharmacy
Categories
Funding
- AstraZeneca
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BACKGROUND: Patients may experience increased risk of adverse drug interactions when statins are administered concomitantly with cytochrome P450 3A4 (CYP3A4) inhibitors. OBJECTIVE: To determine patient numbers in routine clinical practice with concomitant exposure to CYP3A4-metabolized statins and CYP3A4 inhibitors and highlight potential risk for adverse drug interaction. METHODS: Exposure to prescription medications over I year (2005-2006) was evaluated from patient records: US PharMetrics Integrated Patient-Centric administrative claims database and the US General Electric Medical System (GEMS) database. Rates of concomitant prescribing of statins with CYP3A4 inhibitors (listed in United States of America product labels and all identified potential inhibitors) were examined in the cohort overall, in those aged >= 65 years, and in those receiving higher doses of statins. RESULTS: Overall, 951,166 patient records were included (PharMetrics n = 650,825; GEMS, n 300,341). Of these, 792,081 (83%) patients used a CYP3A4-metabolized statin as opposed to a non-CYP3A4-metabolized statin (17%). Findings from both databases were consistent. Overall, 25-30% of patients given a CYP3A4-metabolized statin were concomitantly exposed to a CYP3A4 inhibitor, including approximately 9% concomitantly exposed to a labeled inhibitor, findings consistent with those in patients aged >= 65 years, and patients on higher doses of statins. CONCLUSIONS: Clinicians frequently co-prescribe CYP3A4-metabolized statins with CYP3A4 inhibitors. Physician education regarding the impact of these inhibitors on the metabolism of lovastatin, simvastatin, and atrovastatin is needed. Further studies are also needed to determine whether concomitant administration of a non-CYP3A4-metabolized statin (such as fluvastatin, pravastatin, or rosuvastatin) with a CYP3A4 inhibitor, may reduce adverse event rates in routine clinical practice. (C) 2008 Published by Elsevier Inc. on behalf of National Lipid Association.
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