Macrolide Drug Interactions: An Update

Abstract

Most of the available data regarding macrolide drug interactions are from studies in healthy volunteers and case reports. These data suggest that clarithromycin appears to have an interaction profile similar to that of erythromycin. Given this similarity, it is important to consider the interaction profile of clarithromycin when using erythromycin. This is especially necessary as funds for further studies of a medication available in generic form (e.g., erythromycin) are limited. Azithromycin has produced few clinically significant interactions with any agent cleared through the cytochrome P450 enzyme system. Although the available data are promising, the final test should come from studies conducted in patients who are taking potentially interacting compounds on a chronic basis.

The impact of drug interactions and polypharmacy on antimicrobial therapy in the elderly

“…Macrolides, with the exception of azithromycin, inhibit the CYP3A4, and the risk of interaction is greatest with orally administered substrates, such as erythromycin, clarithromycin and telithromycin, which can inhibit both intestinal and hepatic CYP3A4 [9,32,33]. Increased concentrations of selected CYP3A4 substrates, such as midazolam, cyclosporine, tacrolimus, lovastatin, simvastatin and calcium-channel blockers, may have clinically relevant harmful effects, including excessive sedation and falls from benzodiazepines, nephrotoxicity from immunosuppressive agents, rhabdomyolysis from statins, and hypotension from antihypertensive drugs [9,34,35].…”

“…Increased concentrations of selected CYP3A4 substrates, such as midazolam, cyclosporine, tacrolimus, lovastatin, simvastatin and calcium-channel blockers, may have clinically relevant harmful effects, including excessive sedation and falls from benzodiazepines, nephrotoxicity from immunosuppressive agents, rhabdomyolysis from statins, and hypotension from antihypertensive drugs [9,34,35]. Erythromycin and, to a lesser extent, clarithromycin and telithromycin may prolong prothrombin time in patients on warfarin [9,32,33], with consequent increased risk of haemorrhagic events. Enhanced toxicity of phenytoin, sulphonylureas and theophylline has been reported with concomitant use of macrolides [9,32,33,36].…”

“…Erythromycin and, to a lesser extent, clarithromycin and telithromycin may prolong prothrombin time in patients on warfarin [9,32,33], with consequent increased risk of haemorrhagic events. Enhanced toxicity of phenytoin, sulphonylureas and theophylline has been reported with concomitant use of macrolides [9,32,33,36]. Finally, the inhibition of CYP3A4 by macrolides may also cause fatal drug interactions, such as QTc prolongation leading to torsade de pointe and death due to an increase in levels of some anti-arrhythmics, tricyclic antidepressants and antipsychotic agents [9].…”

Antibiotic Drug Interactions

“…The macrolides (erythromycin and clarithromycin) and ketolides (telithromycin), with the exception of the azalides (azithromycin), are associated with numerous drug interactions [16,17]. The most common mechanism for these interactions involves inhibition of the CYP450 system and PGP.…”

Cytochrom-P450 mediierte Arzneimittelinteraktionen mit Antibiotika

“…Erythromycin hemmt das Isoenzym CYP3A4 und zeigt gemeinsam mit Clarithromycin das höchste Interaktionspotential aller Makrolide (Tabelle 2) [14]. Für Azithromycin und Dirithromycin sind bis dato noch keine klinisch relevanten Interaktionen beschrieben worden [15,16]. Dies dürfte für Azithromycin zum einen in seiner chemischen Struktur begründet sein; Azithromycin weist einen basischen 15-gliedrigen Ring als Grundgerüst auf (Azalid), während die anderen Vertreter einen für Makrolide typischen 14-gliedrigen Ring besitzen [17].…”