p450 - publications

Predict more p450 - ligand interactions now!


1. Pharmacoepidemiol Drug Saf. 2012 Mar 16. doi: 10.1002/pds.3199. [Epub ahead of
print]

Clinical importance of the drug interaction between statins and CYP3A4
inhibitors: a retrospective cohort study in The Health Improvement Network.

Rowan CG, Brunelli SM, Munson J, Flory J, Reese PP, Hennessy S, Lewis J, Mines D,
Barrett JS, Bilker W, Strom BL.

Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
School of Medicine, Philadelphia, PA, USA; Department of Biostatistics and
Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA,
USA; Outcome Sciences, A Quintiles company, Cambridge MA, USA.
crowan@outcome.com.

OBJECTIVE: To compare the relative hazard of muscle toxicity, renal dysfunction,
and hepatic dysfunction associated with the drug interaction between statins and
concomitant medications that inhibit the CYP3A4 isoenzyme. BACKGROUND: Although
statins provide important clinical benefits related to mitigating the risk of
cardiovascular events, this class of medications also has the potential for
severe adverse reactions. The risk for adverse events may be potentiated by
concomitant use of medications that interfere with statin metabolism. METHODS:
Data from The Health Improvement Network (THIN) from 1990 to 2008 were used to
conduct a retrospective cohort study. Cohorts were created to evaluate each
outcome (muscle toxicity, renal dysfunction, and hepatic dysfunction)
independently. Each cohort included new statin initiators and compared the
relative hazard of the outcome. The interaction ratio (I*R) was the primary
contrast of interest. The I*R represents the relative effect of each statin type
(statin 3A4 substrate vs. statin non-3A4 substrate) with a CYP3A4 inhibitor,
independent of the effect of the statin type without a CYP3A4 inhibitor. We
adjusted for confounding variables using the multinomial propensity score.
RESULTS: The median follow-up time per cohort was 1.5 years. There were 7889
muscle toxicity events among 362 809 patients and 792 665 person-years. The
adjusted muscle toxicity I*R was 1.22 (95% confidence interval [CI] = 0.90-1.66).
There were 1449 renal dysfunction events among 272,099 patients and 574 584
person-years. The adjusted renal dysfunction I*R was 0.91 (95%CI = 0.58-1.44).
There were 1434 hepatic dysfunction events among 367 612 patients and 815 945
person-years. The adjusted hepatic dysfunction I*R was 0.78 (95%CI = 0.45-1.31).
CONCLUSIONS: Overall, this study found no difference in the relative hazard of
muscle toxicity, renal dysfunction, or hepatic dysfunction for patients
prescribed a statin 3A4 substrate versus a statin non-3A4 substrate with CYP3A4
inhibitor concomitancy. Copyright © 2012 John Wiley & Sons, Ltd.

Copyright © 2012 John Wiley & Sons, Ltd.

PMID: 22422642 [PubMed - as supplied by publisher]