Is use of nifurtimox for the treatment of Chagas disease compatible with breast feeding? A population pharmacokinetics analysis.
BACKGROUND
Women with Chagas disease receiving treatment with nifurtimox are discouraged from breast feeding. Many patients who would receive treatment with nifurtimox live in extreme poverty, have limited access to resources such as clean water and baby formula and may not have safe alternatives to breast milk.


OBJECTIVE
We aimed to estimate, using limited available pharmacokinetics data, potential infant exposure to nifurtimox through breast milk.


METHODS
Original nifurtimox plasma concentrations were obtained from published studies. Pharmacokinetic parameters were estimated using non-linear mixed-effect modelling with NONMEM V.VI. A total of 1000 nifurtimox plasma-concentration profiles were simulated and used to calculate the amount of drug that an infant would be exposed to, if breast fed 150 ml/kg/day.


RESULTS
Breast milk concentrations on the basis of peak plasma levels (1361 ng/ml) and milk-plasma ratio were estimated. We calculated infant nifurtimox exposure of a breastfed infant of a mother treated with this drug to be below 10% of the maternal weight-adjusted dose, even if milk-plasma ratio were overestimated. Simulation led to similar estimates.


CONCLUSIONS
Risk for significant infant exposure to nifurtimox through breast milk seems small and below the level of exposure of infants with Chagas disease receiving nifurtimox treatment. This potential degree of exposure may not justify discontinuation of breast feeding.
Garcia-Bournissen
Facundo
F
Division of Clinical Pharmacology and Toxicology, Hospital for Sick Children, University of Toronto, 555 University Avenue, 8th Floor, Black Wing, Room 8232, Toronto, ON M5G 1X8, Canada. facundo.garciabournissen@sickkids.ca
Altcheh
Jaime
J
Panchaud
Alice
A
Ito
Shinya
S
D001942:Breast Feeding; D014355:Chagas Disease / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008895:Milk, Human / Q000378:metabolism*; D009547:Nifurtimox / Q000097:blood / Q000493:pharmacokinetics*; D018570:Risk Assessment / Q000379:methods; D014344:Trypanocidal Agents / Q000097:blood / Q000493:pharmacokinetics*
D014344:Trypanocidal Agents; D009547:Nifurtimox