Antituberculosis
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
No reports describing the use of bedaquiline in human pregnancy have been located. The animal data suggest low risk but the absence of human pregnancy experience prevents a full assessment of embryo–fetal risk. Nevertheless, tuberculosis is a severe infection and, if indicated, bedaquiline should not be withheld because of pregnancy.
FETAL RISK SUMMARY
Bedaquiline fumarate is an oral diarylquinoline antimycobacterial drug. It is indicated as part of combination therapy in adults (≥18 years) with pulmonary multidrug-resistant tuberculosis. It is metabolized to an inactive metabolite (M2). Plasma protein binding of bedaquiline is >99.9%. The mean terminal elimination half-life of both bedaquiline and M2 is about 5.5 months, thought to reflect the slow release from peripheral tissues (1).
Reproduction studies have been conducted in rats and rabbits. In these studies, no evidence of fetal harm was found. The plasma exposure in rats was twofold higher (lower in rabbits) than the human plasma exposure (1).
Bedaquiline was not mutagenic or clastogenic in several assays. The drug had no effects on fertility in male and female rats (1).
It is not known if bedaquiline or M2 cross the human placenta. The molecular weight of bedaquiline (about 556) and the very long elimination half-lives of the parent compound and M2 suggest that both may cross to the embryo–fetus. However, the high plasma protein binding might reduce the amount available to cross the placenta.
BREASTFEEDING SUMMARY
No reports describing the use of bedaquiline during breastfeeding have been located. The molecular weight of bedaquiline (about 556) and the very long elimination half-lives (about 5.5 months) of the parent compound and M2 suggest that both may be excreted into breast milk, but the high plasma protein binding might reduce the amount excreted. However, bedaquiline is concentrated in the milk of rats with concentrations 6–12 times the maximum maternal plasma level. If a mother chooses to nurse while receiving the drug, her infant should be observed for nausea, arthralgia, headache, hemoptysis, and chest pain, the most common (≥10%) adverse reactions observed in patients.
Reference
1.Product information. Sirturo. Janssen Therapeutics, 2012.