Effects on fertility: The effects of ceftazidime/avibactam on fertility in humans have not been studied. No data are available on animal studies with ceftazidime. Animal studies with avibactam do not indicate harmful effects with respect to male fertility. Studies in female rats showed a dose-related increase in pre-and post-implantation losses and smaller live litter size at ≥500 mg/kg/day (≥3 times the human therapeutic exposure at 500 mg three times a day, based on AUC).
Use in pregnancy: Ceftazidime: The safety of ceftazidime in pregnancy has not been established, although animal studies have not produced evidence of embryopathic or teratogenic effects attributable to ceftazidime.
Avibactam: Animal studies with avibactam have shown reproductive toxicity without evidence of teratogenic effects.
In pregnant rabbits administered avibactam at 300 and 1000 mg/kg/day (5-21 times the human therapeutic exposure based on AUC), there was a dose-related lower mean fetal weight and delayed ossification, associated with maternal toxicity (decreased food consumption and body weight gain). Plasma exposure levels at maternal and fetal NOAEL (100 mg/kg/day) indicate low margins of safety (1.5 times the human therapeutic exposure based on AUC).
In the rat, no adverse effects were observed on embryofetal development at up to 1000 mg/kg/day (6 times the human therapeutic exposure based on AUC). Following administration of avibactam throughout pregnancy and lactation in the rat, there was no effect on pup survival, growth or development, however there was an increase in incidence of dilation of the renal pelvis and ureters in less than 10% of the rat pups at maternal exposures ≥ 450 mg/kg/day (greater than or equal to approximately 3 times the human therapeutic exposures based on AUC). Ceftazidime/avibactam should only be used during pregnancy if the potential benefit outweighs the possible risk.
Use in lactation: Ceftazidime is excreted in human milk in small quantities.
It is unknown whether avibactam is excreted in human milk. Avibactam was excreted in rat milk (~20% of plasma Cmax), and very low levels were detected in pup plasma (<0.03% of nonclinical maternal plasma Cmax) as a result of exposure from milk.
A risk to newborns/infants cannot be excluded. A decision must be made whether to discontinue breast feeding or to discontinue/abstain from ceftazidime/avibactam therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.