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Drug interactions of macrolides: emphasis on dirithromycin
V S Watkins1, R E Polk, J L Stotka
1Lilly Research Laboratories, Indianapolis, IN 46285, USA.
The Annals of Pharmacotherapy
|March 1, 1997
Summary
Dirithromycin, a new macrolide antibiotic, does not inhibit the cytochrome P450 enzyme system, leading to fewer drug interactions compared to erythromycin and clarithromycin. This macrolide offers a safer alternative for patients on multiple medications.
Area of Science:
- Pharmacology
- Drug Interactions
- Macrolide Antibiotics
Background:
- Erythromycin, a foundational macrolide, interacts with drugs metabolized by the cytochrome P450 enzyme system.
- Newer macrolides aim to reduce or eliminate these clinically significant drug-drug interactions.
- Understanding macrolide-specific interactions is crucial for patient safety.
Purpose of the Study:
- To characterize the drug interaction profile of dirithromycin, a novel macrolide.
- To compare the interaction potential of dirithromycin with other macrolides like erythromycin and clarithromycin.
- To evaluate dirithromycin's impact on cytochrome P450 enzyme activity.
Main Methods:
- Literature review of macrolide drug interactions using MEDLINE (1980-1995).
- Pharmacokinetic and pharmacodynamic studies of dirithromycin with cyclosporine, theophylline, terfenadine, warfarin, and ethinyl estradiol.
- In vitro assessment of dirithromycin's binding to cytochrome P450 enzymes.
Main Results:
- Dirithromycin demonstrated minimal inhibition of cytochrome P450 enzymes, unlike erythromycin and clarithromycin.
- No clinically significant drug interactions were observed between dirithromycin and the tested co-administered drugs.
- Erythromycin significantly altered cyclosporine clearance, while dirithromycin had no significant effect.
Conclusions:
- Dirithromycin does not inhibit the cytochrome P450 enzyme system, indicating a low potential for drug interactions.
- Concomitant administration of dirithromycin with cyclosporine, theophylline, terfenadine, warfarin, or ethinyl estradiol is unlikely to cause significant adverse effects.
- Dirithromycin represents a safer macrolide option for patients requiring concurrent medications.
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