Negligible exposure to nifurtimox through breast milk during maternal treatment for Chagas Disease

Abstract

Background Treatment with nifurtimox (NF) for Chagas disease is discouraged during breast-feeding because no information on NF transfer into breast milk is available. NF is safe and effective for paediatric and adult Chagas disease. We evaluated the degree of NF transfer into breast milk in lactating women with Chagas disease. Patients and methods Prospective study of a cohort of lactating women with Chagas disease. Patients were treated with NF for 1 month. NF was measured in plasma and milk by high performance liquid chromatography (HPLC). Breastfed infants were evaluated at admission, 7 th and 30 th day of treatment (and monthly thereafter, for 6 months). Results Lactating women with chronic Chagas disease (N = 10) were enrolled (median age 28 years, range 17–36). Median NF dose was 9.75 mg/kg/day three times a day (TID). Six mothers had mild adverse drug reactions (ADRs), but no ADRs were observed in any of the breastfed infants. No interruption of breastfeeding was observed. Median NF concentrations were 2.15 mg/L (Inter quartil range (IQR) 1.32–4.55) in milk and 0.30 mg/L (IQR 0.20–0.95) in plasma. Median NF milk/plasma ratio was 16 (range 8.75–30.25). Median relative infant NF dose (assuming a daily breastmilk intake of 150 mL/kg/day) was 6.7% of the maternal dose/kg/day (IQR 2.35–7.19%). Conclusions The low concentrations of NF in breast milk and the normal clinical evaluation of the breastfed babies imply that maternal NF treatment for Chagas disease during breastfeeding is unlikely to lead to clinically relevant exposures in the breastfed infants. Trial registration Clinical trial registry name and registration number: ClinicalTrials.gov NCT01744405 .

WHF IASC Roadmap on Chagas Disease

“…The most frequent and serious are cutaneous, neurologic, hepatic, and hematologic. Anti-parasitic therapy is contraindicated in pregnancy, but may be offered during breastfeeding if indicated [95,96]. Other contraindications include renal or hepatic insufficiency and advanced cardiomyopathy (Figure 9).…”

Biopharmaceutical Characteristics of Nifurtimox Tablets for Age‐ and Body Weight‐Adjusted Dosing in Patients With Chagas Disease

“…9 Nifurtimox passes the placental and blood-brain barriers, 9 and breastfeeding while taking nifurtimox is not recommended owing to its excretion in breast milk. 11 However, a population PK model estimate, 11 subsequently corroborated by a clinical study, 12 determined that nifurtimox levels in breast milk are typically <10% of the maternal weight-adjusted dose and below the levels to which infants being treated with nifurtimox would typically be exposed. 11,12 The drug is rapidly and extensively metabolized, 13 but the metabolic pathways have not been elucidated.…”

“…11 However, a population PK model estimate, 11 subsequently corroborated by a clinical study, 12 determined that nifurtimox levels in breast milk are typically <10% of the maternal weight-adjusted dose and below the levels to which infants being treated with nifurtimox would typically be exposed. 11,12 The drug is rapidly and extensively metabolized, 13 but the metabolic pathways have not been elucidated. It is known that nitroreductases play an important role in the metabolism of nitrofurans such as nifurtimox, 14 but detailed characterization of its main metabolites in humans is yet to be reported.…”

Review of pharmacological options for the treatment of Chagas disease

“…Treatment with BZN and NF is contraindicated during pregnancy in most guidelines, due to limited evidence on safety, yet there is evidence of low concentration of BZN or NF in breastmilk with no risk to infants during lactation [29][30][31] .…”