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Drug interactions of macrolides: emphasis on dirithromycin.
Ann Pharmacother. 1997 Mar; 31(3):349-56.AP

Abstract

OBJECTIVE

To describe the drug interactions of dirithromycin, a new macrolide, and to compare them with those of other macrolides.

DATA SOURCES

A literature search was performed using MEDLINE to identify articles published between January 1980 and July 1995 concerning the drug interactions of macrolides. Published abstracts were also examined. All studies using dirithromycin were performed under the sponsorship of Eli Lilly and Company.

DATA SYNTHESIS

Erythromycin, the first macrolide discovered, is metabolized by the cytochrome P450 enzyme system. By decreasing their metabolism, erythromycin can interact with other drugs metabolized by the cytochrome P450 enzymes. The lack of such interactions would be a desirable feature in a newer macrolide. We describe studies performed to detect any interactions of dirithromycin with cyclosporine, theophylline, terfenadine, warfarin, and ethinyl estradiol. The studies showed that dirithromycin, like azithromycin, is much less likely to cause the interactions detected with clarithromycin and erythromycin. A review of the literature showed differences among macrolides in their abilities to inhibit cytochrome P450 enzymes and, thus, to cause drug-drug interactions. Erythromycin and clarithromycin inhibit cytochrome P450 enzymes, and have been implicated in clinically significant interactions. Azithromycin and dirithromycin neither inhibit cytochrome P450 enzymes nor are implicated in clinically significant drug-drug interactions.

CONCLUSIONS

Dirithromycin, a new macrolide, does not inhibit the cytochrome P450 enzyme system. The concomitant use of dirithromycin with cyclosporine, theophylline, terfenadine, warfarin, or ethinyl estradiol was studied in pharmacokinetic and pharmacodynamic studies. In vitro, dirithromycin did not bind cytochrome P450. In healthy subjects, erythromycin increases the clearance of cyclosporine by 51%, whereas dirithromycin causes no significant changes in the pharmacokinetics of cyclosporine. In kidney transplant recipients, administration of dirithromycin was associated with a significant (p < 0.003) decrease of 17.4% in the clearance of cyclosporine. In patients taking low-dose estradiol, the administration of dirithromycin caused a significant (p < 0.03) increase of 9.9% in the clearance of ethinyl estradiol; escape ovulation did not occur. Unlike erythromycin and clarithromycin, dirithromycin had no significant effects on the pharmacokinetics of theophylline, terfenadine, or warfarin. The alterations typical of drug interactions that are based on inhibition of the cytochrome P450 system occurring with erythromycin and clarithromycin were not observed with dirithromycin.

Authors+Show Affiliations

Lilly Research Laboratories, Indianapolis, IN 46285, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Review

Language

eng

PubMed ID

9066944

Citation

Watkins, V S., et al. "Drug Interactions of Macrolides: Emphasis On Dirithromycin." The Annals of Pharmacotherapy, vol. 31, no. 3, 1997, pp. 349-56.
Watkins VS, Polk RE, Stotka JL. Drug interactions of macrolides: emphasis on dirithromycin. Ann Pharmacother. 1997;31(3):349-56.
Watkins, V. S., Polk, R. E., & Stotka, J. L. (1997). Drug interactions of macrolides: emphasis on dirithromycin. The Annals of Pharmacotherapy, 31(3), 349-56.
Watkins VS, Polk RE, Stotka JL. Drug Interactions of Macrolides: Emphasis On Dirithromycin. Ann Pharmacother. 1997;31(3):349-56. PubMed PMID: 9066944.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Drug interactions of macrolides: emphasis on dirithromycin. AU - Watkins,V S, AU - Polk,R E, AU - Stotka,J L, PY - 1997/3/1/pubmed PY - 1997/3/1/medline PY - 1997/3/1/entrez SP - 349 EP - 56 JF - The Annals of pharmacotherapy JO - Ann Pharmacother VL - 31 IS - 3 N2 - OBJECTIVE: To describe the drug interactions of dirithromycin, a new macrolide, and to compare them with those of other macrolides. DATA SOURCES: A literature search was performed using MEDLINE to identify articles published between January 1980 and July 1995 concerning the drug interactions of macrolides. Published abstracts were also examined. All studies using dirithromycin were performed under the sponsorship of Eli Lilly and Company. DATA SYNTHESIS: Erythromycin, the first macrolide discovered, is metabolized by the cytochrome P450 enzyme system. By decreasing their metabolism, erythromycin can interact with other drugs metabolized by the cytochrome P450 enzymes. The lack of such interactions would be a desirable feature in a newer macrolide. We describe studies performed to detect any interactions of dirithromycin with cyclosporine, theophylline, terfenadine, warfarin, and ethinyl estradiol. The studies showed that dirithromycin, like azithromycin, is much less likely to cause the interactions detected with clarithromycin and erythromycin. A review of the literature showed differences among macrolides in their abilities to inhibit cytochrome P450 enzymes and, thus, to cause drug-drug interactions. Erythromycin and clarithromycin inhibit cytochrome P450 enzymes, and have been implicated in clinically significant interactions. Azithromycin and dirithromycin neither inhibit cytochrome P450 enzymes nor are implicated in clinically significant drug-drug interactions. CONCLUSIONS: Dirithromycin, a new macrolide, does not inhibit the cytochrome P450 enzyme system. The concomitant use of dirithromycin with cyclosporine, theophylline, terfenadine, warfarin, or ethinyl estradiol was studied in pharmacokinetic and pharmacodynamic studies. In vitro, dirithromycin did not bind cytochrome P450. In healthy subjects, erythromycin increases the clearance of cyclosporine by 51%, whereas dirithromycin causes no significant changes in the pharmacokinetics of cyclosporine. In kidney transplant recipients, administration of dirithromycin was associated with a significant (p < 0.003) decrease of 17.4% in the clearance of cyclosporine. In patients taking low-dose estradiol, the administration of dirithromycin caused a significant (p < 0.03) increase of 9.9% in the clearance of ethinyl estradiol; escape ovulation did not occur. Unlike erythromycin and clarithromycin, dirithromycin had no significant effects on the pharmacokinetics of theophylline, terfenadine, or warfarin. The alterations typical of drug interactions that are based on inhibition of the cytochrome P450 system occurring with erythromycin and clarithromycin were not observed with dirithromycin. SN - 1060-0280 UR - https://www.unboundmedicine.com/medline/citation/9066944/Drug_interactions_of_macrolides:_emphasis_on_dirithromycin_ L2 - https://journals.sagepub.com/doi/10.1177/106002809703100314?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -