Antibiotic
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of telithromycin in human pregnancy have been located. The animal reproduction data suggest low risk, but the absence of human pregnancy experience prevents a more complete assessment. Although there are no other agents in the ketolide class, telithromycin is a chemical derivative of erythromycin, a macrolide anti-infective that is considered compatible in pregnancy. There is currently no evidence that macrolides are associated with developmental toxicity. However, telithromycin may cause severe hepatocellular hepatitis that can be fatal (1). The hepatotoxicity has special significance for pregnant women because liver toxicity sometimes occurs in pregnancy (e.g., viral hepatitis, fatty liver of pregnancy, preeclampsia, and HELLP [hemolysis, elevated liver enzymes, and low platelets] syndrome). Therefore, until there are human pregnancy data, the best course is to avoid the use of telithromycin in pregnancy.
FETAL RISK SUMMARY
Telithromycin, a ketolide, is a semisynthetic antibacterial agent that is a derivative of erythromycin. The chemical structure of telithromycin differs from the macrolide group.
The antibacterial is indicated for the treatment of community-acquired pneumonia (mild to moderate severity). Telithromycin is partially metabolized to inactive metabolites. Plasma protein binding is 60%–70%, primarily to albumin. The terminal elimination half-lives after single and multiple doses are about 7 and 10 hours, respectively (2).
Reproduction studies have been conducted in rats and rabbits. No evidence of structural defects was found when doses that were about 1.8 and 0.49 times, respectively, the daily human dose based on BSA (DHD) were given to these species. No adverse effects on prenatal or postnatal development on rat pups were observed at 1.5 times the DHD. However, doses higher than 1.8 and 0.49 times, respectively, the DHD in rats and rabbits were associated with maternal toxicity and delayed fetal maturation (2).
Carcinogenicity studies have not been conducted, but tests for genotoxicity were negative. Doses that were about 0.61 times the DHD had no effect on fertility in rats. Higher doses, 1.8–3.6 times the DHD, did impair fertility but also caused toxicity in both male and female rats (2).
It is not known if telithromycin crosses the human placenta. The molecular weight (about 812), moderate plasma protein binding, and the long elimination half-life suggest that the antibacterial agent will cross to the embryo–fetus.
BREASTFEEDING SUMMARY
No reports describing the use of telithromycin during human lactation have been located.
The molecular weight (about 812), moderate plasma protein binding (60%–70%), and long elimination half-life (≤10 hours) suggest that telithromycin will be excreted into breast milk. The effect of this exposure on a nursing infant is unknown. Although modification of the bowel flora, direct effects, and interference with the interpretation of culture results if a fever workup is required are potential effects, a closely related antibacterial, erythromycin is considered compatible with nursing. When taking this drug and nursing, a mother should observe her infant for the most common adverse effects reported in adults, such as diarrhea, nausea, vomiting, headache, and dizziness.
References
1.Ross DB. The FDA and the case of Ketek. N Engl J Med 2007;356:1601–4.
2.Product information. Ketek. Sanofi-Aventis U.S., 2007.