Azithromycin,
clarithromycin,
dirithromycin, josamycin, midecamycin, rokitamycin, spiramycin, and
telithromycin normally only cause modest changes in
theophylline levels or do not interact at all. However, there are unexplained and isolated case reports of
theophylline toxicity with josamycin and
clarithromycin. Roxithromycin usually has no relevant interaction but a significant increase in
theophylline levels was seen in one study.
The situation with roxithromycin is uncertain since only one study has suggested an interaction, but it would be prudent to be alert for the need to reduce the
theophylline dosage. It would also seem prudent to monitor the outcome of the use of the other
macrolides because a few patients, especially those with
theophylline levels at the high end of the therapeutic range, may need some small
theophylline dosage adjustments. In the case of
azithromycin, care should be taken in adjusting the dose based on
theophylline levels taken after about 5 days of concurrent use, as they may only be a reflection of a transient drop. In addition,
acute infection per se may alter
theophylline pharmacokinetics.