Sulfadoxine and Pyrimethamine and Breastfeeding

Summary of use during lactation

Because there is little published experience with sulfadoxine during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. The manufacturer states that the combination of sulfadoxine-pyrimethamine is contraindicated for prophylaxis during nursing and in children under 2 months of age. However, some authors have found no contraindication to the use of sulfadoxine-pyrimethamine during breastfeeding.[1,2] It has been suggested that maternal pyrimethamine clearance might be increased during lactation, but data are insufficient to make a definitive conclusion.[3,4] Sulfadoxine-pyrimethamine prophylaxis of the mother should be discontinued at the first appearance in the infant of jaundice, skin rash, if a significant reduction in the count of any formed blood elements is noted, or upon the occurrence of active bacterial or fungal infections.

Drug levels in milk and infant serum

Maternal Levels. Relevant published information on sulfadoxine was not found as of the revision date. Pyrimethamine milk levels have been reported to range from 0.2 to 0.26 mcg/L at 6 hours after doses of 25, 50 or 75 mg in 6 women. Milk levels ranged from 0.125 to 0.155 mcg/L 24 hours after the dose and 0.095 to 0.0105 mcg/L at 48 hours.[5,6] Three women were given a single dose of pyrimethamine 12.5 mg orally 2 to 5 days postpartum. Milk samples were obtained periodically for about 9 days after the dose. Assuming a daily intake of 1 L of milk, the infants would receive 0.14, 0.21 and 0.34 mg in milk over the study period. These values equate to an average of 46% of the maternal weight-adjusted dosage.[7] Infant Levels. Relevant published information was not found as of the revision date.

Effects in breastfed infants

Administration of pyrimethamine to mothers of 26 predominantly breastfed infants 2 to 6 months old who were infected with malaria was curative in the infants.[6] The regimen consisted of 75 mg followed by a subsequent dose of 50-75 mg 4 to 7 days later. The efficacy apparently is related to breastfeeding habits, because infants in another tribal group who breastfed their infants less extensively were not protected.[5] An additional case report indicates that a maternal dose of 75 mg orally followed by 25 mg weekly cured malaria in her infant and protected her breastfed infant against becoming infected with malaria for 6 months.[7] No adverse effects were reported in any of the infants. A study of women with HIV infection being treated for presumptive malaria included 12 nursing mothers who were taking the sulfadoxine-pyrimethamine combination. The drug combination appeared to reduce breastmilk viral load less than chloroquine treatment. No mention was made of the effects in breastfed infants.[8] 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). Eight mothers also took sulfadoxine-pyrimethamine. No serious adverse events were reported in any of the breastfed infants.[9,10]

Effects on lactation and breastmilk

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

Alternative drugs to consider

Chloroquine, Mefloquine

References

1. ChattopadhyayR MahajanB KumarS Assessment of safety of the major antimalarial drugs. Expert Opin Drug Saf 2007 6 505 21 17877439 PubMed
2. PetersPJ ThigpenMC PariseME Safety and toxicity of sulfadoxine/pyrimethamine: implications for malaria prevention in pregnancy using intermittent preventive treatment. Drug Saf 2007 30 481 501 17536875 PubMed
3. de KockM TarningJ BarnesKI Response to "Lactation status and studies of pyrimethamine pharmacokinetics in pregnancy". CPT Pharmacometrics Syst Pharmacol 2017 6 731 29052341 PubMed
4. SalmanS DavisTME Regarding "Lactation status and studies of pyrimethamine pharmacokinetics in pregnancy". CPT Pharmacometrics Syst Pharmacol 2017 6 730 29064165 PubMed
5. ClydeDF An examination of factors involved in the transfer of pyrimethamine in human milk. East Afr Med J 1957 34 81 5 13437933 PubMed
6. ClydeDF PressJ ShuteGT Transfer of pyrimethamine in human milk. J Trop Med Hyg 1956 59 277 84 13385913 PubMed
7. ClydeDF Prolonged malaria prophylaxis through pyrimethamine in mothers' milk. East Afr Med J 1960 37 659 60 13694157 PubMed
8. SemrauK KuhnL KasondeP Impact of chloroquine on viral load in breast milk. Trop Med Int Health 2006 11 800 3 16772000 PubMed
9. 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
10. 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