Rhabdomyolysis a result of azithromycin and statins: an unrecognized interaction

center dot Rhabdomyolysis is a serious but rare adverse effect of statins. center dot The mechanism of rhabdomyolysis with statins is poorly defined, but the occurrence is known to increase with dose/ concentration. center dot Some macrolides are known to interact with statins; however, azithromycin has not been described to interact with statins with the exception of two literature case reports. WHAT THIS STUDY ADDS center dot A case series in the World Health Organization Adverse Drug Reaction (WHO-ADR) database was suggestive of a possible drug interaction between statins and azithromycin with rhabdomyolysis. center dot A disproportionality measure, Omega, was shown to identify previously not recognized suspected drug interactions within the WHO-ADR dataset. AIMS In a systematic screening of the World Health Organization Adverse Drug Reaction database, VigiBase, in July 2008, a measure of association used to detect interactions (Omega) highlighted azithromycin with the individual statins atorvastatin, lovastatin and simvastatin and rhabdomyolysis. The aim was to examine all reports including rhabdomyolysis-azithromycin and statins in VigiBase to assess if the data were suggestive of an interaction. METHODS The individual case reports in VigiBase and the original files were reviewed. In order to investigate the reporting over time for rhabdomyolysis with azithromycin and statins to VigiBase, Omega values were generated retrospectively. RESULTS The reporting over time showed that rhabdomyolysis under concomitant use of azithromycin and statins was reported more often than expected from 2000 and onwards in Vigibase. After exclusion of possible duplicates and follow-up reports, 53 cases from five countries remained. Rhabdomyolysis occurred shortly after initiation of azithromycin in 23% of cases. In 11 patients an interaction had been suggested by the reporter. With the exception of one patient, the statin doses reported were within the recommended daily doses. CONCLUSIONS Case reports in VigiBase are suggestive that interactions between azithromycin and statins resulting in rhabdomyolysis may occur. This analysis showed the potential of the newly developed disproportionality measure, Omega, which can help to identify drug interactions in VigiBase in the future. The results also showed that reviewing spontaneous reports can add information to drug interactions not established previously.