Macrolide drug interactions: An update

OBJECTIVE: To describe the current drug interaction profiles for the common ly used macrolides in the US and Europe, and to comment on the clinical imp act of these interactions. DATA SOURCES: A MEDLINE search (1975-1998) was performed to identify all pe rtinent studies, review articles, and case reports. When appropriate inform ation was not available in the literature, data were obtained from the prod uct manufacturers. STUDY SELECTION: All available data were reviewed to provide an unbiased ac count of possible drug interactions. DATA EXTRACTION: Data for some of the interactions were not available from the literature, but were available from abstracts or company-supplied mater ials. Although the data were not always explicit, the best attempt was made to deliver pertinent information that clinical practitioners would need to formulate practice opinions. When more in-depth information was supplied i n the form of a review or study report, a thorough explanation of pertinent methodology was supplied. DATA SYNTHESIS: Several clinically significant drug interactions have been identified since the approval of erythromycin. These interactions usually w ere related to the inhibition of the cytochrome P450 enzyme systems, which are responsible for the metabolism of many drugs. The decreased metabolism by the macrolides has in some instances resulted in potentially severe adve rse events. The development and marketing of newer macrolides are hoped to improve the drug interaction profile associated with this class. However, t his has produced variable success. Some of the newer macrolides demonstrate d an interaction profile similar to that of erythromycin; others have shown improved profiles. The most success in avoiding drug interactions related to the inhibition of cytochrome P450 has been through the development of th e azalide subclass, of which azithromycin is the first and only to be marke ted. Azithromycin has not been demonstrated to inhibit the cytochrome P450 system in studies using a human liver microsome model, and to date has prod uced none of the classic drug interactions characteristic of the macrolides . CONCLUSIONS: Most Of the available data regarding macrolide drug interactio ns are from studies in healthy volunteers and case reports. These data sugg est that clarithromycin appears to have an interaction profile similar to t hat of erythromycin. Given this similarity, it is important to consider the interaction profile of clarithromycin when using erythromycin. This is esp ecially necessary as funds for further studies of a medication available in generic form (e.g., erythromycin) are limited, Azithromycin has produced f ew clinically significant interactions with any agent cleared through the c ytochrome P450 enzyme system. Although the available data are promising, th e final test should come from studies conducted in patients who are taking potentially interacting compounds on a chronic basis.