According to some authorities: Use is contraindicated during the first trimester of pregnancy; this drug should be used during the second and third trimesters of 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.

Comments:
-There are risks associated with untreated lower genital tract infection during pregnancy.
-Based on findings in rodents, this drug may impair fertility in males of reproductive potential; not known if effects on fertility are reversible.

Animal studies have revealed evidence of a slightly higher incidence of fetal mortality. After oral administration to pregnant mice during organogenesis, no embryofetal toxicity or malformations were observed at highest dose of 2500 mg/kg (about 6.3-fold the highest human therapeutic dose based on body surface area [BSA] conversions); after oral administration to pregnant rats during organogenesis, a slight increase in fetal mortality was seen at maternal dose of 500 mg/kg (2.5-fold the highest human therapeutic dose based on BSA conversions) and no biologically-relevant neonatal developmental effects were observed in surviving pups after maternal doses as high as 600 mg/kg (3-fold the highest human therapeutic dose based on BSA conversions). This drug crosses the placenta and enters fetal circulation. 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.

See references

This drug may continue to appear in breast milk for more than 72 hours after use. Amounts of this drug in milk are less than doses given to infants; infant plasma levels have not been measured during breastfeeding.

As with metronidazole, there has been concern about exposure of healthy infants to this drug via breast milk, due to possible mutagenicity and carcinogenicity. Expert opinions vary regarding use during longer-term therapy while breastfeeding; however, avoiding nursing for 3 days after a single dose should allow milk levels to decline to negligible values.

On day 4 postpartum, 3 women started twice-daily oral dosing. On day 7, milk samples were collected 2, 5, and 9 hours after dosing; breast milk levels ranged between 5.8 and 12.7 mg/L.

After cord clamping, 24 women who delivered by cesarean section were given a single 500 mg IV dose. Colostrum drug levels averaged 5.8 mg/L at 12 hours after the dose, 3.5 mg/L at 24 hours, 1.2 mg/L at 48 hours, and 0.3 mg/L at 72 hours after the dose; the drug was barely detectable 96 hours after the dose. There were only slight differences between levels in foremilk and hindmilk.

After cord clamping, 5 women who delivered by cesarean section were given a single 1600 mg IV dose. Milk levels and volumes were measured for 96 hours after the dose. The authors concluded that milk levels would be low enough to start breastfeeding 72 hours after the dose.

Breastfeeding is not recommended during use of this drug and for 72 hours after the last dose; other drugs are available for some conditions.

Excreted into human milk: Yes

Comments:
-The effects in the nursing infant are unknown; however, they are likely similar to those of metronidazole (closely related), such as increased risk of oral and rectal Candida infections.
-A nursing mother may choose to pump and discard her milk during therapy and for 72 hours after the last dose to minimize exposure to the breastfeeding infant.

See references