Animal studies have failed to reveal evidence of teratogenicity but have revealed evidence of increased embryonic loss. Imipenem and cilastatin (alone or in combination) administered parenterally during organogenesis to mice, rats, rabbits, and monkeys at doses 0.4 to 2.9 times the recommended human dose (RHD) (based on body surface area [BSA]) showed no drug-induced fetal malformations; imipenem-cilastatin administered IV to cynomolgus monkeys at doses about 0.6 times the RHD (based on BSA) showed increased embryonic loss. There are no controlled data in human pregnancy.

AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.

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.

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

AU TGA pregnancy category: B3
US FDA pregnancy category: Not assigned.

Risk summary: Insufficient data available on use of this drug in pregnant women to inform a drug-related risk.

See references

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.

LactMed and other experts: Use is considered acceptable.
-According to some authorities: Breastfeeding is not recommended during use of this drug.
-According to some authorities: Benefit should outweigh risk.

Excreted into human milk: Yes (in small amounts)

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