Because of the possibility of hemolytic anemia due to immature erythrocyte enzyme systems (glutathione instability):
-Use is contraindicated in pregnant patients during labor and delivery, or when onset of labor is imminent.
---According to some authorities: Use is contraindicated in pregnant patients at term (38 to 42 weeks gestation).
---According to some authorities: Caution is recommended when used at term.
This drug should be used during pregnancy only if clearly needed; it should be used at the lowest dose appropriate for specific indication only after careful assessment.

AU TGA pregnancy category: A (short-term therapy)
US FDA pregnancy category:
-Capsules: B
-Oral suspension: Not assigned.

Risk summary: Malformative risk with use of this drug in pregnant women is unlikely.

Animal studies have failed to reveal evidence of fetotoxicity or teratogenicity. This drug crosses the placenta. There are no controlled data in human pregnancy; however, this drug has been in extensive clinical use for many years and its suitability in human pregnancy has been well documented. Thus far, studies have not shown a potential for this drug to cause birth defects.

In man, this drug can reduce sperm counts and produce abnormal testicular histology suggestive of arrested spermatogenesis.

AU TGA pregnancy category A: Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed.

US FDA pregnancy category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

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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LactMed: Use is considered acceptable while breastfeeding older infants, but alternative agents are preferred in mothers nursing infants younger than 8 days or infants with glucose-6-phosphate dehydrogenase (G6PD) deficiency at any age.
-According to some experts: Use is considered acceptable if infant is healthy and older than 1 month; use should be avoided if infant has G6PD deficiency or is younger than 1 month.
-According to some authorities: Use should be temporarily avoided while breastfeeding infants with known/suspected erythrocyte enzyme deficiency (including G6PD deficiency); according to at least 1 manufacturer, caution is recommended while breastfeeding such infants.
-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.

Excreted into human milk: Yes (trace amounts)

Comments:
-Although the amount of this drug excreted in breast milk after normal therapeutic doses is considered negligible, the possibility of hemolytic anemia due to immature enzyme systems in the early neonatal period should be considered when using this drug in nursing mothers.
-The effects in the nursing infant are unknown; infants should be observed for possible diarrhea.

The time of peak amounts in milk depends on food taken with the drug and dosage form of the drug. Rapid-release capsules (macrocrystals) reach peak milk levels about 1 to 2 hours after the dose with food or 4 hours after a high-fat meal. The sustained-release product (macrocrystals-monohydrate) has not been studied, but probably has a delayed peak milk time difficult to predict in individual mothers.

In 1 early report, milk samples were collected from several women (administered 100 mg orally 4 times a day) in the first few days postpartum; random milk samples were tested, and this drug was undetectable (less than 2 mg/L) in 20 samples measured.

A second study found milk levels ranging from 0 to 0.5 mg/L in 4 women (time postpartum not provided) 2 hours after a single 200 mg dose was given orally during therapy with 100 mg 4 times a day; in 5 others administered 100 mg orally 4 times a day, no drug was detected in milk levels (assay limit not provided).

At 3 to 6 days postpartum, 6 women were administered 50 or 100 mg (macrocrystalline formulation) orally 3 times a day. This drug was undetectable (less than 10 mcg/L) in all women before the first dose on day 2 of administration with breakfast (fat content not provided); peak milk levels occurred 1 to 2 hours after the dose. Mothers taking the 50 mg regimen had milk levels averaging 0.49 mg/L (range: 0.2 to 0.7 mg/L) 3 hours after the dose and those taking the 100 mg regimen had milk levels of 1.19 mg/L (range: 0.62 to 2.22 mg/L) at 3 hours. According to author calculation, between 0.06% and 0.28% of a dose was excreted into milk during the 6 hours after a dose.

At 8 to 26 weeks postpartum, 4 women were administered a single 100 mg dose (as macrocrystals) orally with a high-fat meal; peak milk levels occurred 4 to 6 hours after the dose and averaged 2.7 mg/L (range: 2.2 to 3.2 mg/L). Milk levels were higher than serum levels and much higher than predicted at all times, indicating active transport into milk; even so, an exclusively breastfed infant would receive only 0.2 mg/kg/day or about 6% of the weight-adjusted maternal dose.

In a prospective follow-up study, 6 nursing mothers reported taking this drug (dose and formulation not provided); 2 mothers reported diarrhea in their infants, but no rashes or candidiasis were reported among the exposed infants. A decreased milk supply was reported by 1 nursing mother, but it is not known if there was a causal relationship.

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