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Zidovudine glucuronide mean Cmax and AUC increased by 16% (CV 61%) and 8.0% (CV 32%), respectively. Doses of 1200 mg/ day azithromycin for 14 days in 6 subjects increased Cmax of concurrently administered didanosine (200 mg q. 12h) by 44% (54% CV) and AUC by 14% (23% CV). However, none of these changes were significantly different from those produced in a parallel placebo control group of subjects. Preliminary data suggest that coadministration of azithromycin and rifabutin did not markedly affect the mean serum concentrations of either drug. Administration of 250 mg azithromycin daily for 10 days (500 mg on the first day) produced mean concentrations of azithromycin 1 day after the last dose of 53 ng/ mL when coadministered with 300 mg daily rifabutin and 49 mg/ mL when coadministered with placebo. Mean concentrations 5 days after the last dose were 23 ng/ mL and 21 ng/ mL in the two groups of subjects. Administration of 300 mg rifabutin for 10 days produced mean concentrations of rifabutin one half day after the last dose of 60 mg/ ml when coadministered with daily 250 mg azithromycin and 71 ng/ mL when coadministered with placebo. Mean concentrations 5 days after the last dose were 8.1 ng/ mL and 9.2 ng/ mL in the two groups of subjects. Text Continues Below
The following drug interactions have not been reported in clinical trials with azithromycin; however, no specific drug interaction studies have been performed to evaluate potential drug-drug interaction. Nonetheless, they have been observed with macrolide products. Until further data are developed regarding drug interactions when azithromycin and these drugs are used concomitantly, careful monitoring of patients is advised: Digoxin– elevated digoxin levels. Ergotamine or dihydroergotamine– acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia. Triazolam– decrease the clearance of triazolam and thus may increase the pharmacologic effect of triazolam. Drugs metabolized by the cytochrome P 450 system– elevations of serum carbamazepine, cyclosporine, hexobarbital, and phenytoin levels. Laboratory Test Interactions: There are no reported laboratory test interactions. Carcinogenesis, Mutagenesis, Impairment of Fertility: Long-term studies in animals have not been performed to evaluate carcinogenic potential. Azithromycin has shown no mutagenic potential in standard laboratory tests: mouse lymphoma assay, human lymphocyte clastogenic assay, and mouse bone marrow clastogenic assay. Pregnancy Teratogenic Effects Pregnancy Category B Reproduction studies have been performed in rats and mice at doses up to moderately maternally toxic dose levels (i. e., 200 mg/ kg/ day). These doses, based on a mg/ m 2 basis, are estimated to be 4 and 2 times, respectively, the human daily dose of 500 mg. With regard to the MAC treatment dose of 600 mg daily, on a mg/ m 2 /day basis, the doses in rats and mice are approximately 3.3 and 1.7 times the human dose, respectively. With regard to the MAC prophylaxis dose of 1200 mg weekly, on a mg/ m 2 /day basis, the doses in rats and mice are approximately 2 and 1 times the human dose, respectively. No evidence of impaired fertility or harm to the fetus due to azithromycin was found. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, azithromycin should be used during pregnancy only if clearly needed. Nursing Mothers It is not known whether azithromycin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when azithromycin is administered to a nursing woman. Pediatric Use In controlled clinical studies, azithromycin has been administered to pediatric patients ranging in age from 6 months to 12 years. Page: << Prev | 1 | 2 | 3 | 4 | 5
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