Animal studies have revealed evidence of teratogenicity. In pregnant rats administered this drug orally during organogenesis, maternal weight loss, reduced fetal weights, smaller litter sizes, fetal anasarca, and fetal eye abnormalities (anophthalmia, microphthalmia) were observed at doses of 50 to 150 mg/kg/day (about 1 to 3 times the maximum recommended human dose [MRHD] based on whole body surface area [BSA] comparisons); no maternal or fetal toxicity was observed at 50 and 15 mg/kg/day, respectively (about equal to MRHD based on BSA comparison and about 0.3 times the MRHD based on whole BSA comparison, respectively). In pregnant rabbits administered this drug orally during organogenesis, maternal toxicity (including reduced weight gain, reduced food intake), abortions, and fetal ventricular septal defect were observed at doses of 7.5 to 25 mg/kg/day (about 0.3 to 1 times the MRHD based on whole BSA comparison); the doses not associated with maternal and fetal toxicity were 7.5 and 2.5 mg/kg/day, respectively (about 0.3 and 0.1 times the MRHD based on whole BSA comparison, respectively). There are no controlled data in human pregnancy.

Based on findings in rats, this drug may impair fertility in males of reproductive potential. In rats, the effects on fertility were reversible 22 weeks after dosing; however, the effects in humans are unknown.

There are inconsistent data regarding chronic Chagas disease during pregnancy; some studies showed increased risk of pregnancy loss, prematurity, and neonatal morality while other studies did not. Since pregnancy data are inconsistent and chronic Chagas disease is generally not life-threatening, use of this drug is not recommended due to risk of embryofetal toxicity.

While acute symptomatic Chagas disease is rare in pregnant women, symptoms may be serious or life-threatening. Cases have been reported of pregnant women with life-threatening symptoms related to acute Chagas disease using this drug. If acute symptomatic Chagas disease develops during pregnancy, the risks/benefits of therapy to the mother and fetus should be assessed individually.

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.

Pregnant women should be apprised of the potential harm to the fetus.
-Acute symptomatic Chagas disease: This drug should not be used during pregnancy unless the benefit outweighs the risk to the mother and fetus.
-Chronic Chagas disease: Use is not recommended.

US FDA pregnancy category: Not assigned.

Risk summary: May cause fetal harm (based on animal studies); insufficient human data available on use of this drug in pregnant women to inform a drug-related risk.

Comments:
-There are risks to the fetus associated with Chagas disease.
-Patients of childbearing potential: Pregnancy testing is recommended. Patients should be advised to use effective contraception during therapy and for 5 days after the last dose; local protocol should be consulted regarding contraception timing.

See references

According to limited data based on samples of breast milk, amounts of this drug in human milk correspond to infant doses of 5.5% to 17% of the maternal weight-adjusted dose; the milk/plasma ratio ranges between 0.3 to 2.79.

The amount of this drug excreted into milk is much lower than the amount used to treat infants. Use of this drug in nursing mothers is considered acceptable due to low drug levels in breast milk and safety when given directly to infants.

In 10 women using 5 to 10 mg/kg/day to treat Chagas disease, 17 breast milk samples were collected at unspecified times. Drug levels in breast milk ranged from undetectable (less than 0.3 mg/L) to 9.8 mg/L; mean level was 4.1 mg/L. An exclusively breastfed infant would receive 0.6 and 1.5 mg/kg/day using the mean and maximum levels, respectively; such values are much less than the therapeutic dose of 5 mg/kg/day, which has been used safely in neonates with congenital Chagas disease.

In 10 nursing women using 300 or 400 mg (median: 5.65 mg/kg) orally twice a day for 30 days, 16 breast milk samples were collected at 9 days (median; range: 6 to 34 days) of therapy. Infant age was 5.2 months (median; range: 20 days to 13 months); 5 infants were exclusively breastfed while the others were partially breastfed. The drug level in breast milk was 3.8 mg/L (median; range: 0.3 to 5.9 mg/L). The calculated infant dose was 0.65 mg/kg/day (median), which is about 10% of the dose used for Chagas disease treatment in infants; this dose correlated to 12.3% (range: 1.3% to 17%) of the maternal weight-adjusted daily dose. None of the infants had any side effects attributable to this drug.

Breast milk samples were provided for analysis by 4 women with Chagas disease using 5 to 10 mg/kg/day (in 2 divided doses) after 4 to 10 days of therapy; timing of sample collection with regard to dosing was not provided. Breast milk drug levels ranged from nonquantifiable (less than 0.88 mg/L) to 7.1 mg/L.

A postpartum woman with Chagas disease was treated with 5 mg/kg/day, starting 1 month postpartum and continuing for 30 days; she continued to breastfeed her infant (extent not provided). According to the authors, no side effects were seen in the infant.

LactMed: Use is generally considered acceptable.
WHO: Safety has not been established.
-According to some authorities: Breastfeeding is not recommended during use of this drug.

Excreted into human milk: Yes

Comments:
-The effects in the nursing infant are unknown.
-Some authorities and experts advise patients not to breastfeed due to the potential for serious side effects and transmission of Chagas disease.

See references