An Evaluation of Macrolide Drug-Drug Interactions for Quality in the Literature

Abstract

OBJECTIVES: To evaluate the quality of evidence in the literature substantiating major drug-drug interactions of the macrolide antibiotics azithromycin, clarithromycin, and erythromycin with digoxin, ergot alkaloids, and pimozide. METHODS: In this descriptive retrospective analysis, a list of articles reporting on each drug-drug interaction was compiled from the online databases Medline and International Pharmaceutical Abstracts, and the drug compendia Micromedex and Facts & Comparisons. The studies included in this analysis were primary literature reports, written in English, and consisted of human subjects. All studies included were evaluated using a 5-point quality of evidence scale developed in the Netherlands to assess drug-drug interactions (van Roon scale). This scale rates the study type from lowest to highest quality, from zero to four. Case reports were additionally analyzed using the Drug Interaction Probability Scale (DIPS). The DIPS tool uses 10 questions to evaluate the probability that an adverse event is caused by a drug-drug interaction. RESULTS: Thirty-seven studies met the selection criteria. There were 28 studies involving digoxin, two studies involving pimozide and seven studies involving ergot alkaloids. The mean quality of evidence score on the van Roon scale was 2.3 + 0.75, where digoxin studies had a score of 2.3 + 0.74, ergot alkaloids had a score of 1.9 + 0.38 and pimozide only had two studies with evidence scores of 2 and 4. Sixty-two percent of the studies reviewed were case reports. CONCLUSION: The reports substantiating some drug-drug interactions may be of low quality and few in number.