This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus.

US FDA pregnancy category: Not assigned.

Risk summary: Potential risks to pregnancy and the fetus based on embryonic loss and fetal abnormalities observed in animal studies; insufficient data available on use of this drug in pregnant women to inform a drug-related risk.

Comments:
-According to some authorities: If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risks to pregnancy and the fetus.

Animal studies with imipenem-cilastatin have failed to reveal evidence of teratogenicity but have revealed evidence of increased embryonic loss; animal studies with relebactam have revealed evidence of fetal abnormalities. Imipenem and cilastatin (alone or in combination) administered parenterally during organogenesis to mice, rats, rabbits, and monkeys at doses 1 to 5 times the maximum recommended human dose (MRHD) (based on body surface area [BSA] comparison) showed no drug-induced fetal malformations; imipenem-cilastatin administered IV to cynomolgus monkeys at doses similar to the MRHD (based on BSA comparison) showed increased embryonic loss. Relebactam administered parenterally during organogenesis to mice was associated with a non-dose responsive increase in the litter incidence of cleft palate at plasma relebactam exposure about equal to human exposure at the MRHD and an increased percent litter incidence of total skeletal malformations at plasma exposure about 6 times human exposure at the MRHD; relebactam administered during organogenesis to rats and rabbits was not associated with maternal or embryofetal toxicity at doses corresponding to plasma AUC exposures about 7 and 24 times, respectively, human plasma AUC at the MRHD. Studies in pregnant rats and rabbits showed placental transfer of relebactam, with fetal plasma levels up to 5% to 6% of maternal levels observed. There are no controlled data in human pregnancy.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

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IMIPENEM-CILASTATIN:
Imipenem 500 mg and cilastatin 500 mg were infused IV over 30 minutes in 12 women. Milk imipenem levels were 0.21 to 0.52 mg/L between 1 and 5 hours after dosing in 10 of the women; imipenem was usually detectable in only 1 to 3 of the samples taken hourly for 6 hours. In 1 woman, imipenem was undetectable (less than 0.2 mg/L) in all samples collected up to 6 hours after dosing; another woman had a detectable milk imipenem level of 1.84 mg/L only at 4 hours after dosing. Cilastatin was undetectable (less than 0.5 mg/L) in all milk samples collected from all women.

Imipenem 500 mg and cilastatin 500 mg were infused IV over 30 minutes in 11 women; 76 milk samples were collected over the 6 hours after dosing. Imipenem was detectable in milk primarily at 2 to 4 hours after dosing, reaching the highest milk levels an average of 3 hours after dosing. All milk levels were less than 1 mg/L each time up to 6 hours after dosing; imipenem was undetectable in the milk of some women. Cilastatin was not measured.

RELEBACTAM:
This component was administered IV to lactating rats (450 mg/kg/day); relebactam was excreted into the milk at levels about 5% of maternal plasma levels.

LactMed: Use is considered acceptable.
-According to some authorities: A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother and the benefit of breastfeeding for the child.

Excreted into human milk: Yes (imipenem, cilastatin [both in small amounts]); Unknown (relebactam)
Excreted into animal milk: Yes (relebactam)

Comments:
-Developmental and health benefits of breastfeeding should be considered as well as the mother's clinical need for this drug.
-The effects in the nursing infant are unknown; potential side effects in the breastfed child due to this drug or the mother's underlying condition should be considered.
-According to limited data, low levels of imipenem in milk are not expected to cause harmful effects in the nursing infant.
-Disruption of infant's gastrointestinal flora (resulting in diarrhea or thrush) reported occasionally with beta-lactams, but such effects have not been adequately evaluated.

See references