Successful strategy to improve the specificity of electronic statin-drug interaction alerts

Eur J Clin Pharmacol. 2009 Nov;65(11):1149-57. doi: 10.1007/s00228-009-0704-x. Epub 2009 Jul 30.


Purpose: A considerable weakness of current clinical decision support systems managing drug-drug interactions (DDI) is the high incidence of inappropriate alerts. Because DDI-induced, dose-dependent adverse events can be prevented by dosage adjustment, corresponding DDI alerts should only be issued if dosages exceed safe limits. We have designed a logical framework for a DDI alert-system that considers prescribed dosage and retrospectively evaluates the impact on the frequency of statin-drug interaction alerts.

Methods: Upper statin dose limits were extracted from the drug label (SPC) (20 statin-drug combinations) or clinical trials specifying the extent of the pharmacokinetic interaction (43 statin-drug combinations). We retrospectively assessed electronic DDI alerts and compared the number of standard alerts to alerts that took dosage into account.

Results: From among 2457 electronic prescriptions, we identified 73 high-risk statin-drug pairs. Of these, SPC dosage information classified 19 warnings as inappropriate. Data from pharmacokinetic trials took quantitative dosage information more often into consideration and classified 40 warnings as inappropriate. This is a significant reduction in the number of alerts by 55% compared to SPC-based information (26%; p < 0.001).

Conclusion: This retrospective study of pharmacokinetic statin interactions demonstrates that more than half of the DDI alerts that presented in a clinical decision support system were inappropriate if DDI-specific upper dose limits are not considered.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Decision Support Systems, Clinical*
  • Drug Interactions*
  • Drug Therapy, Combination / adverse effects
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics
  • Medical Order Entry Systems*
  • Medication Errors / prevention & control
  • Retrospective Studies


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors