Original article
Concomitant use of statins and CYP3A4 inhibitors in administrative claims and electronic medical records databases

https://doi.org/10.1016/j.jacl.2008.10.007Get rights and content

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 1 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.

Section snippets

Data sources

Exposure to prescription medications was approximated using prescriptions dispensed from the PharMetrics Integrated Patient-Centric database and prescriptions written from the GEMS database. Eligible patients were aged ≥18 years and exposed to ATV, FLV, LOV, PRV, RSV, SMV, or SMV/EZE during the study period.

The PharMetrics Patient-Centric database includes longitudinal, integrated patient-level medical and pharmacy claims from 47 primarily private, as well as public (Medicare supplemental and

Results

Known CYP3A4 inhibitors, including those listed in the precautions sections of United States product labels, and potential CYP3A4 inhibitors identified,28, 29 are shown in Figure 1.

Discussion

Adverse drug reactions account for 3–7% of medical hospital admissions,30 and are the sixth leading cause of death, contributing to substantial morbidity, particularly in the elderly.31, 32 A propensity for physicians to repeatedly prescribe potentially interacting drug combinations has been shown previously. For example, records from computerized drug prescription screening systems and general practice databases have been used to demonstrate persistent and repeated co-prescribing of

Financial disclosures

Drs. Ming, Gandhi, Marotti, Miles, and Ke are employees of AstraZeneca. Dr. Davidson is an investigator for the AstraZeneca METEOR trial and is a consultant for AstraZeneca, Merck/Schering-Plough, Pfizer, and Takeda Pharmaceuticals. Dr. McKenney has provided consultancy for Abbott Laboratories, Agerion, AstraZeneca, Merck & Co, and Daiichi Sankyo.

Acknowledgment

The authors acknowledge editorial support from Carl Felton of Prime Medica, which was funded by AstraZeneca. Pia Pollack of AstraZeneca provided scientific input and reviewed the manuscript. Opinions expressed remain those of the named authors.

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