This drug should not be used during pregnancy unless the benefit outweighs the risk to the fetus.

US FDA pregnancy category: Not assigned.

Risk summary: Based on animal studies, this drug may cause fetal harm when used during pregnancy; insufficient data available on use of this drug in pregnant women to inform a drug-related risk.

Comments:
-Maternal and/or embryo/fetal risk due to the mother's underlying condition should be considered.
-A pregnancy exposure registry is available.
-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 harm to the fetus.
-Pregnancy testing should be performed in patients of childbearing potential before starting this drug.
-Since this drug may cause fetal harm when used during pregnancy, patients of childbearing potential should be advised to use effective contraception during therapy and for 6 months after the last dose.
-Due to the potential for genotoxicity, male patients with female partners of childbearing potential should use condoms during therapy and for 3 months after the last dose.
-Local protocol should be consulted regarding contraception timing.

Animal studies have revealed evidence of fetal harm and impaired male fertility. After oral administration to pregnant mice, rats, and rabbits during organogenesis, this drug was associated with reduced fetal body weights in mice, reduced maternal and fetal body weights in rats, and abortions, reduced maternal weight gain, and reduced numbers of live fetuses in rabbits at doses about equal to the maximum recommended human dose (MRHD) (based on surface area comparison) in rodents and 2 times the MRHD (based on surface area comparison) in rabbits; incidence of fetal skeletal malformation (fusion of caudal vertebral bodies) increased in rabbits at doses about 0.2 times the MRHD. In rats, 5% to 20% of male offspring in all the treatment groups for this drug showed slightly small testes. Based on findings in rodents, this drug may impair fertility in males of reproductive potential; effects on fertility were not reversible in 75% of the animals at 11 weeks after dosing. This drug passes the placental barrier. There are no controlled data in human pregnancy.

Published data from case-control and observational studies on chronic Chagas disease during pregnancy showed inconsistent results. Some studies had increased risk of pregnancy loss, prematurity, and neonatal mortality in pregnant women with chronic Chagas disease; however, these outcomes were not observed in other studies. In general, chronic Chagas disease is not immediately life-threatening. Because pregnancy results were inconsistent, treatment of chronic Chagas disease during pregnancy is not recommended due to risk of embryofetal toxicity from this drug.

Acute symptomatic Chagas disease is rare in pregnant women, but symptoms may be serious or life-threatening. If a pregnant woman presents with acute symptomatic Chagas disease, the risks/benefits of treatment with this drug to the mother and fetus should be assessed on an individual basis.

There is a pregnancy safety study for this drug. If this drug is used during pregnancy, or if the patient becomes pregnant while taking or within 6 months after the last dose of this drug, healthcare providers should report nifurtimox exposure by calling 1-888-842-2937.

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

According to published literature, this drug is present in human breast milk with an estimated infant daily dose of less than 15% of the recommended daily dose for pediatric patients with Chagas disease. There were no reports of side effects in the small number of infants breastfed by mothers using this drug.

Limited data indicates maternal doses up to 15 mg/kg/day do not cause any serious side effects in breastfed infants. Breast milk levels and computer simulation showed the dose an exclusively breastfed infant would receive through breast milk would be much less than the dose used to treat Chagas disease in neonates.

A computer simulation (using pharmacokinetic data from adults and assuming milk-plasma ratios of 1) estimated a median infant dose of 0.19% of the maternal weight-adjusted dose; assuming milk-plasma ratios of 6 estimated a maximum infant dose of 3.1% of the maternal weight-adjusted dose.

After 4 to 10 days of therapy, breast milk samples were provided by 4 women with Chagas disease who received 10 to 15 mg/kg/day (in 3 divided doses); the timing of the sample with respect to dosing was not provided. Breast milk levels of this drug ranged from nonquantifiable (less than 0.55 mg/L) to 8.2 mg/L.

At steady state, 10 women who were receiving 9.75 mg/kg/day (median dose) donated 1 or 2 milk samples at various times after dosing; the drug level in milk averaged 2.15 mg/L (interquartile range [IQR]: 1.32 to 4.55 mg/L). According to author estimation, infants would receive 0.5 mg/kg/day (median dose), equivalent to a median weight-adjusted maternal dose of 6.7% (IQR: 2.35% to 7.19%).

In the Democratic Republic of the Congo, 33 infants breastfed (extent not provided) by hospitalized mothers using this drug were followed; 30 mothers took 30 doses (a full course) of this drug (15 mg/kg/day orally) and all received 14 doses of eflornithine (400 mg/kg/day IV for 7 days) for human African trypanosomiasis (sleeping sickness). Nursing mothers also took an average of 4 other concomitant medications (including amoxicillin, ciprofloxacin, metronidazole, sulfamethoxazole-trimethoprim, aspirin, and diclofenac [1 patient each]; hydrocortisone, promethazine, and quinine [2 patients each]; levamisole [6 patients]; pyrimethamine-sulfadoxine [8 patients]; dipyrone [13 patients]; acetaminophen [16 patients]; and mebendazole [17 patients]). No serious side effects were reported in any of the breastfed infants.

Benefit should outweigh risk.
-According to some experts: Breastfeeding is not considered contraindicated during use of this drug.

Excreted into human milk: Yes

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.
-Infants exposed to this drug through breast milk should be monitored for vomiting, rash, decreased appetite, pyrexia, and irritability.

See references