Antibiotic (Tetracycline)
PREGNANCY RECOMMENDATION: Human Data Suggest Risk in 2nd and 3rd Trimesters
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
No reports describing the use of tigecycline in human pregnancy have been located. In one animal species, exposures close to those obtained in humans that did not cause maternal toxicity did result in reduced fetal weight and minor skeletal anomalies. Moreover, tigecycline crosses the placentas of rats and rabbits and enters fetal tissues, including fetal bony structures (1). Similar to tetracyclines, tigecycline can permanently discolor the teeth if used in the second half of pregnancy (1). Inadvertent or planned use in the 1st trimester probably does not represent a major risk to the embryo or fetus, but use in later trimesters should be avoided.
FETAL RISK SUMMARY
Tigecycline is a glycylcycline, broad-spectrum antibacterial agent with bacteriostatic activity that is given by IV infusion. It is structurally related to the tetracycline class of antibiotics and may have similar adverse effects. Tigecycline undergoes partial metabolism. The elimination half-life after a single IV dose is about 27 hours, whereas after multiple dosing the half-life is about 42 hours. The primary route of elimination is by biliary excretion. The in vitro plasma protein binding ranges from about 71% to 89% (1).
Reproduction studies have been conducted in rats and rabbits. No teratogenic effects were observed in either species at exposures about 5 times and equal to, respectively, the human daily dose based on AUC (HDD). However, these exposures were associated with slight reductions in fetal weights and an increased incidence of minor skeletal anomalies (delays in bone ossification). The exposure in rabbits was maternally toxic and was associated with an increased incidence of fetal loss (1).
Studies for carcinogenicity have not been conducted with tigecycline, but tests for mutagenicity and clastogenicity were negative. No effects on reproductive performance or fertility were observed in male and female rats given doses resulting in exposures that were 5 times the HDD (1).
Tigecycline crosses the placentas of animals (1). However, it is not known if the drug crosses the human placenta. The molecular weight (about 586), prolonged elimination half-life, and wide distribution in tissues suggest that the antibiotic will cross to the embryo–fetus. Moreover, tetracycline is known to cross the human placenta resulting in fetal toxicity.
BREASTFEEDING SUMMARY
No reports describing the use of tigecycline during human lactation have been located. The molecular weight (about 586), prolonged elimination half-life, and wide distribution in tissues suggest that the antibiotic will be excreted into breast milk. However, the oral bioavailability of tigecycline is such that there might be little or no systemic exposure. Even if the oral bioavailability in infants is negligible, the presence of the antibiotic in milk could cause three potential problems: modification of bowel flora, direct effects on the infant’s gut, and interference with the interpretation of culture results if a fever workup is required.
Reference
1.Product information. Tygacil. Wyeth Pharmaceuticals, 2005.