Nifurtimox and Breastfeeding

Summary of use during lactation

Limited information indicates that maternal doses of nifurtimox up to 15 mg/kg daily produce do not cause any adverse serious effects in breastfed infants. Breastmilk levels and a computer simulation found that the dose that an exclusively breastfed infant would receive through breastmilk would be much less than the dose given to treat Chagas disease in newborn infants. Other authors consider that breastfeeding is not contraindicated during the use of nifurtimox.[1,2]

Drug levels in milk and infant serum

Maternal Levels. A computer simulation using pharmacokinetic data from adults and assuming milk-plasma ratios of 1 resulted in an estimated median infant dose of 0.19% of the maternal weight-adjusted dosage. Assuming milk-plasma ratios of 6 resulted in an estimated maximum infant dose of 3.1% of the maternal weight-adjusted dosage.[3] Four women with Chagas disease were treated with nifurtimox 10 to 15 mg/kg daily in 3 divided doses provided breastmilk samples for analysis after 4 to 10 days of therapy. The timing of the sample with respect to doses was not reported. Breastmilk concentrations of nifurtimox ranged from nonquantifiable (<0.55 mg/L) to 8.2 mg/L.[4] Ten women were receiving a median dose of nifurtimox of 9.75 mg/kg daily donated 1 or 2 milk samples at various times after a dose at steady state. The median nifurtimox concentration in milk was 2.15 mg/L (interquartile range 1.32 to 4.55 mg/L). The authors estimated that infants would receive a median daily dosage of 0.5 mg/kg, which is equal to a median weight-adjusted maternal dose of 6.7% (interquartile range 2.35 to 7.19%).[5] Infant Levels. Relevant published information was not found as of the revision date.

Effects in breastfed infants

A cohort of 33 infants who were breastfed (extent not stated) by hospitalized mothers taking nifurtimox was followed in the Democratic Republic of the Congo. Thirty mothers took a full course of 30 doses of oral nifurtimox 15 mg/kg daily and all received 14 doses of intravenous eflornithine 400 mg/kg daily for 7 days for human African trypanosomiasis. (sleeping sickness). Nursing mothers also took a median of 4 other concomitant medications, including amoxicillin, ciprofloxacin, metronidazole, trimethoprim-sulfamethoxazole, aspirin, and diclofenac (1 patient each); hydrocortisone, promethazine and quinine (2 patients each); levamisole (6 patients); sulfadoxine-pyrimethamine (8 patients); dipyrone (13 patients); acetaminophen (16 patients); and mebendazole (17 patients). No serious adverse events were reported in any of the breastfed infants.[6-8]

Effects on lactation and breastmilk

Relevant published information was not found as of the revision date.

References

1. Sankale M, Brun A. Les medicaments des parasitoses tropicales au cours de la grossesse et de l'allaitement. (2 parts). Le Concours Medical 1991;14:2335-9; 248-51.
2. BarennesH ChoonaraI Breast feeding and drug therapy in neglected diseases. Arch Dis Child 2010 95 222 3 20308339 PubMed
3. García-BournissenF AltchehJ PanchaudA Is use of nifurtimox for the treatment of Chagas disease compatible with breastfeeding? A population pharmacokinetics analysis. Arch Dis Child 2010 95 224 8 19948512 PubMed
4. PadróJM Pellegrino VidalRB EchevarriaRN Development of an ionic-liquid-based dispersive liquid-liquid microextraction method for the determination of antichagasic drugs in human breast milk: Optimization by central composite design. J Sep Sci 2015 38 1591 600 25711461 PubMed
5. MoroniS MarsonME MoscatelliG Negligible exposure to nifurtimox through breast milk during maternal treatment for Chagas Disease. PLoS Negl Trop Dis 2019 13 e0007647 31415566 PubMed
6. SchmidC KuemmerleA BlumJ In-hospital safety in field conditions of nifurtimox eflornithine combination therapy (NECT) for T. b. gambiense sleeping sickness. PLoS Negl Trop Dis 2012 6 e1920 23209861 PubMed
7. KuemmerleA SchmidC KandeV Prescription of concomitant medications in patients treated with nifurtimox eflornithine combination therapy (NECT) for T.b. gambiense second stage sleeping sickness in the Democratic Republic of the Congo. PLoS Negl Trop Dis 2020 14 e0008028 31986140 PubMed
8. KuemmerleA SchmidC BernhardS Effectiveness of nifurtimox eflornithine combination therapy (NECT) in T. b. gambiense second stage sleeping sickness patients in the Democratic Republic of Congo: Report from a field study. PLoS Negl Trop Dis 2021 15 e0009903 34748572 PubMed