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Rhabdomyolysis reports show interaction between simvastatin and CYP3A4 inhibitors
Author(s) -
Rowan Christopher,
Brinker Allen D.,
Nourjah Parivash,
Chang Jennie,
Mosholder Andrew,
Barrett Jeffrey S.,
Avigan Mark
Publication year - 2009
Publication title -
pharmacoepidemiology and drug safety
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.023
H-Index - 96
eISSN - 1099-1557
pISSN - 1053-8569
DOI - 10.1002/pds.1711
Subject(s) - rhabdomyolysis , medicine , simvastatin , concomitant , statin , adverse effect , adverse event reporting system , cyp3a4 , pravastatin , ambulatory , atorvastatin , pharmacology , cholesterol , cytochrome p450 , metabolism
Purpose To assess spontaneous reports of rhabdomyolysis associated with simvastatin (SV) and pravastatin (PV) for evidence of CYP3A4 interaction. Clinical trial results advocate cholesterol lowering in high‐risk patients including diabetics and the elderly. Given the association between advancing age, metabolic, and cardiovascular disease, many patients are treated with concomitant medications upon statin initiation. Although statins are generally safe, minor and severe adverse reactions arise, especially when given to patients taking concomitant medications that inhibit the statin clearance and lead to increased statin plasma concentration. Methods We conducted a comparative case series of rhabdomyolysis reports associated with SV and PV. Domestic spontaneous reports were obtained from the FDA's Adverse Event Reporting System (AERS). Drug utilization data were obtained from IMS HEALTH and the National Ambulatory Medical Care Survey (NAMCS). Adverse event reporting rates (AER) and ratios (AERR) of rhabdomyolysis associated with SV and PV—with and without stratification by CYP3A4 inhibitor concomitancy were determined. Results Stratification by CYP3A4 inhibitor concomitancy did not change the rhabdomyolysis AER for PV with or without a CYP3A4 inhibitor (2.4 cases and 3.1 cases per 10 million Rx, respectively). However, stratification of SV reports with or without a concomitant CYP3A4 inhibitor resulted in a rhabdomyolysis AER (38.4 and 6.0 cases per 10 million Rx, respectively). The corresponding AERR with or without a CYP3A4 inhibitor were 0.77 for PV and 6.43 for SV. Conclusions Spontaneous adverse event reports provide evidence of increased risk for rhabdomyolysis based on interaction between SV and selected CYP3A4 inhibitors. Copyright © 2009 John Wiley & Sons, Ltd.