Antituberculosis Agent
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity Contraindicated (Patients with HIV Infection)
PREGNANCY SUMMARY
No reports describing the use of rifabutin in human pregnancy have been located. The animal data are suggestive of low risk, but the absence of human pregnancy experience prevents an assessment of the embryo–fetal risk. However, the maternal benefit appears to outweigh the unknown risk to the embryo or fetus, so therapy should not be withheld because of pregnancy.
FETAL RISK SUMMARY
Rifabutin is an oral semi-synthetic ansamycin antibiotic that is derived from rifamycin S. It is indicated for the prevention of disseminated Mycobacterium avium complex (includes M. avium and M. intracellulare) disease in patients with advanced human HIV infection. Five metabolites have been identified, one of which is active (contributes up to 10% of the antimicrobial activity). Rifabutin is moderately (about 85%) bound to plasma proteins and has a mean terminal half-life of 45 hours (1).
Rifabutin was not carcinogenic in mice and rats at doses about 32 and 12 times, respectively, the recommended human daily dose (RHDD). In addition, no mutagenicity was observed in several assays (1).
Reproduction tests have been conducted in rats and rabbits. In rats, doses up to 40 times the RHDD were not teratogenic, but the highest dose caused a decrease in fetal viability. At 8 times the RHDD, an increase in fetal skeletal variants was observed. In rabbits, no teratogenic effects were observed with doses up to 40 times the RHDD. A dose 16 times the RHDD was maternal toxic and resulted in an increase in fetal skeletal anomalies (1).
It is not known if rifabutin or its active metabolite crosses the human placenta. The molecular weight of the parent compound (about 847), moderate plasma protein binding, high lipid solubility, and prolonged terminal half-life suggest that passage to the embryo–fetus will occur.
Rifabutin induces the metabolism of ethinyl estradiol and norethindrone, thereby decreasing the efficacy of oral contraceptives (1). Therefore, additional, nonhormonal methods of birth control should be used during treatment with this antibiotic.
BREASTFEEDING SUMMARY
No reports describing the use of rifabutin during human lactation have been located. The molecular weight (about 847), moderate plasma protein binding, and prolonged terminal half-life suggest that excretion into milk should be expected. Milk may be stained a brown-orange color. The effect of this exposure on a nursing infant is unknown but serious toxicity (e.g., leukopenia, neutropenia, rash) is a potential complication. If the drug is used during breastfeeding, monitoring for these toxicities should be considered. Moreover, rifabutin is indicated for the prevention of disseminated M. avium complex in patients with advanced HIV infection, and women with HIV should not breastfeed.
Reference
1.Product information. Mycobutin. Pharmacia & Upjohn, 2004.