Azithromycin + Rifabutin = Unknown or no reaction

Study Design

This multicenter study evaluated the tolerance and potential pharmacokinetic interactions between azithromycin and rifabutin in volunteers with or without human immunodeficiency virus infection. Pharmacokinetic sampling was performed on days 14, 15, and 42.

Study Results

No significant differences in baseline characteristics were found between the pairs of randomization groups receiving either the high- or low-dose regimens. Daily dosing with the combination of azithromycin and rifabutin was poorly tolerated, primarily because of gastrointestinal symptoms and neutropenia. No significant pharmacokinetic interactions were found between these drugs. The observed pharmacokinetic parameters are consistent with those reported in previous studies of rifabutin (7, 16) and azithromycin (5)

Study Conclusions

References

Hafner R. Tolerance and pharmacokinetic interactions of rifabutin and azithromycin. Antimicrob Agents Chemother. 2001; 5: 1572-7.

Study Design

A 14-day, randomized, open, phase I clinical trial was designed to examine possible pharmacokinetic interactions between rifabutin and two other antibiotics, azithromycin and clarithromycin, used in the treatment of Mycobacterium avium complex infections. Thirty healthy male and female volunteers were divided into five groups of six participants each: 18 received 300 mg/day of rifabutin, 12 in combination with therapeutic doses of either azithromycin or clarithromycin; the remaining 12 received azithromycin or clarithromycin alone. On day 10 the study was terminated because of adverse events, including severe neutropenia. Fourteen participants who received rifabutin developed neutropenia, including all 12 participants who received azithromycin or clarithromycin concomitantly.

Study Results

Analyses of serum revealed no apparent pharmacokinetic interaction between azithromycin and rifabutin. However, the mean concentrations of rifabutin and 25-O-desacetyl-rifabutin (an active metabolite) in participants who received clarithromycin and rifabutin concomitantly were more than 400 and 3,700, respectively, of concentrations in those who received rifabutin alone.

Study Conclusions

Physicians should be aware that recommended prophylactic doses of rifabutin may be associated with severe neutropenia within 2 weeks after initiation of therapy, and all patients receiving rifabutin, especially with clarithromycin, should be monitored carefully for neutropenia.

References

Apseloff G. Comparison of azithromycin and clarithromycin in their interactions with rifabutin in healthy volunteers. J Clin Pharmacol. 1998; 9: 830-5.

Study Design

This multicenter study evaluated the tolerance and potential pharmacokinetic interactions between azithromycin and rifabutin in volunteers with or without human immunodeficiency virus infection. Pharmacokinetic sampling was performed on days 14, 15, and 42.

Study Results

No significant differences in baseline characteristics were found between the pairs of randomization groups receiving either the high- or low-dose regimens. Daily dosing with the combination of azithromycin and rifabutin was poorly tolerated, primarily because of gastrointestinal symptoms and neutropenia. No significant pharmacokinetic interactions were found between these drugs. The observed pharmacokinetic parameters are consistent with those reported in previous studies of rifabutin (7, 16) and azithromycin (5)

Study Conclusions

References

Apseloff G. Comparison of azithromycin and clarithromycin in their interactions with rifabutin in healthy volunteers. J Clin Pharmacol. 1998; 9: 830-5.