Zerbaxa Use In Pregnancy & Lactation

Pregnancy: Pregnancy Category B.
There are no adequate and well-controlled trials in pregnant women with either ceftolozane or tazobactam. Because animal reproduction studies are not always predictive of human response, ZERBAXA should be used during pregnancy only if the potential benefit outweighs the possible risk.
Embryo-fetal development studies performed with intravenous ceftolozane in mice and rats with doses up to 2000 and 1000 mg/kg/day, respectively, revealed no evidence of harm to the fetus. The mean plasma exposure (AUC) values associated with these doses are approximately 3.5 (mice) and 2 (rats) times the mean daily human ceftolozane exposure at the highest recommended human dose of 2 grams every 8 hours. It is not known if ceftolozane crosses the placenta in animals.
In a pre-postnatal study in rats, intravenous ceftolozane administered during pregnancy and lactation (Gestation Day 6 through Lactation Day 20) was associated with a decrease in auditory startle response in postnatal Day 60 male pups at maternal doses of greater than or equal to 300 mg/kg/day. The plasma exposure (AUC) associated with the NOAEL dose of 100 mg/kg/day in rats is lower than the mean daily human ceftolozane exposure at the highest recommended human dose of 2 grams every 8 hours.
In an embryo-fetal study in rats, tazobactam administered intravenously at doses up to 3000 mg/kg/day (approximately 10 times the highest recommended human dose of 1 gram every 8 hours based on body surface area comparison) produced maternal toxicity (decreased food consumption and body weight gain) but was not associated with fetal toxicity. In rats, tazobactam was shown to cross the placenta. Concentrations in the fetus were less than or equal to 10% of those found in maternal plasma.
In a pre-postnatal study in rats, tazobactam administered intraperitoneally twice daily at the end of gestation and during lactation (Gestation Day 17 through Lactation Day 21) produced decreased maternal food consumption and body weight gain at the end of gestation and significantly more stillbirths with a tazobactam dose of 1280 mg/kg/day (approximately 4 times the highest recommended human dose of 1 gram every 8 hours based on body surface area comparison). No effects on the development, function, learning or fertility of F1 pups were noted, but postnatal body weights for F1 pups delivered to dams receiving 320 and 1280 mg/kg/day tazobactam were significantly reduced 21 days after delivery. F2-generation fetuses were normal for all doses of tazobactam. The NOAEL for reduced F1 body weights was considered to be 40 mg/kg/day, a dose lower than the highest recommended human dose of 1 gram every 8 hours based on body surface area comparison.
Nursing Mothers: It is not known whether ceftolozane or tazobactam is excreted in human milk. Because many drugs are excreted in human milk, exercise caution when administering ZERBAXA to a nursing woman.