[Risk of pharmacological interactions due to the co-administration of statins and cytochrome P450 isoenzyme 3A4-metabolized drugs: multicentre, crossover study]

Med Clin (Barc). 2014 Nov 18;143(10):427-32. doi: 10.1016/j.medcli.2013.07.030. Epub 2013 Nov 9.
[Article in Spanish]

Abstract

Background and objectives: Statins are safe but have a significant potential for pharmacological interactions. The objective of the study was to evaluate the prevalence of potential interactions throughout the cytochrome P450 isoenzyme 3A4 (CYP3A4) system in a large sample of statin-treated subjects and to determine which factors, from the patient and the physician, were associated with a higher risk of interactions.

Patients and methods: This is an observational, cross-over, population study that included 7,880 subjects treated with statins. Both data from patients and from the1,681 participating physicians were recorded and analyzed.

Results: Fifty-nine percent of the participants were receiving a statin metabolized by the CYP3A4, and 21.5% of all participants received a drug, different from a statin, metabolized by the CYP3A4. There were no differences in the frequency of utilization of statins metabolized or not by the CYP3A4 in relation to the simultaneous prescription of drugs metabolized by the same pathway (22 vs. 21%, respectively). Globally, 12.9% of all participants were at risk of an interaction. These patients were older, received a higher number of drugs and had more comorbidity. Sixty percent of the physicians mentioned that the possibility of an interaction greatly conditioned their selection of a particular statin. Likewise, 56% of them had software that alerted of possible interactions. These aspects, however, did not influence the number of patients at risk of interactions.

Conclusion: The proportion of statin-treated patients at risk of interaction is elevated. Physicians do not usually pay attention to this possibility despite having available alert software and therapeutic alternatives.

Keywords: Citocromo 450; Cytochrome 450; Drug interactions; Estatinas; Interacciones farmacológicas; Isoenzima 3A4; Isoenzyme 3A4; Statins.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Distribution
  • Aged
  • Aged, 80 and over
  • Biotransformation
  • Cross-Over Studies
  • Cross-Sectional Studies
  • Cytochrome P-450 CYP3A / metabolism*
  • Decision Making, Computer-Assisted
  • Drug Interactions
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / metabolism
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Isoenzymes / metabolism
  • Logistic Models
  • Male
  • Middle Aged
  • Polypharmacy*
  • Practice Patterns, Physicians' / statistics & numerical data*
  • Risk Assessment
  • Spain

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Isoenzymes
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human