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Using nitrofurantoin while breastfeeding a newborn
Jamie Zao, Gideon Koren, MD FRCPC FACMT and Pina Bozzo
My patient has a urinary tract infection and is currently breastfeeding. Her son is only 3 weeks old. Is nitrofurantoin a safe antibiotic for treatment?
The use of nitrofurantoin in breastfeeding mothers is generally safe, as only small amounts transfer into the breast milk. Despite the lack of documented reports, there is a risk of hemolytic anemia in all newborns exposed to nitrofurantoin owing to their glutathione instability, especially in infants with glucose-6-phosphate dehydrogenase deficiency. Although some suggest that nitrofurantoin be avoided in infants younger than 1 month, studies have noted that glutathione stability might be established by the eighth day of life. In infants younger than 1 month, an alternative antibiotic might be preferred; however, if an alternative were not available, the use of nitrofurantoin would not be a reason to avoid breastfeeding. In any such case the suckling infant should be monitored by his or her physician.
Ma patiente souffre d'une infection des voies urinaires et allaite actuellement. Son fils n'est âgé que de 3 semaines. La nitrofurantoïne est-elle un antibiotique sécuritaire comme traitement?
L'utilisation de la nitrofurantoïne par des mères qui allaitent est généralement sécuritaire, car seulement de petites quantités passent dans le lait maternel. Malgré la rareté des rapports documentés, il y a un risque d'anémie hémolytique chez tous les nouveau-nés exposés à la nitrofurantoïne en raison de l'instabilité de leur glutathion, surtout chez ceux ayant une insuffisance en glucose-6-phosphate déshydrogénase. Quoique certains fassent valoir qu'il faudrait éviter la nitrofurantoïne chez des nourrissons de moins de 1 mois, des études ont permis de constater que la stabilité du glutathion pourrait être établie dès le huitième jour de vie. Si le nourrisson a moins de 1 mois, un autre antibiotique pourrait être envisagé; toutefois, si une autre option n'était pas disponible, l'utilisation de la nitrofurantoïne ne serait pas une raison pour éviter l'allaitement maternel. Dans un tel cas, l'enfant allaité devrait être surveillé par son médecin.
Urinary tract infections in the 30 days postpartum have been reported to occur at rates of 2.8% following cesarean section and 1.6% following vaginal birth. 1
Nitrofurantoin is an antibiotic that has bactericidal activity against common urinary pathogens. Although its mechanism of action is not entirely clear, it is thought to inhibit several bacterial enzyme systems and interfere with bacterial metabolism and cell-wall synthesis. 2 It is detected at high levels in the urine; however, levels in plasma and whole blood are usually low and often undetectable. 2
When considering the safety of taking medications while breastfeeding, an infant's exposure to the medication via breast milk is estimated by calculating the weight-adjusted dose, also referred to as the relative infant dose. A dose of less than 10% of the maternal weight-adjusted dose is generally considered less likely to increase the risk of adverse effects above that in an infant who is receiving the drug for therapeutic indications. 3
Human studies in breast milk
Nitrofurantoin is actively transported into breast milk, likely through the BCRP (breast cancer resistance protein) transporter. 4 Older studies suggest that nitrofurantoin concentrations in breast milk are low, although the reported values are inconsistent. Two studies reported undetectable levels in breast milk-one in which 20 women took 100-mg doses 4 times a day, 5 another in which 5 women each took a single 100-mg dose. 6 In the latter study, an additional 2 of 4 women also had undetectable levels in breast milk following a 200-mg dose. However, the other 2 women had relative infant doses of 1.3% and 2.25%.6 A 1990 study also reported less than 0.12% and 0.29% of the maternal dose in breast milk 6 hours after the fourth doses of 50 mg and 100 mg of nitrofurantoin, respectively. 7 In a more recent prospective single-dose pharmacokinetic human study, 4 healthy lactating women 8 to 26 weeks postpartum were each administered a single 100-mg dose of nitrofurantoin. A mean milk concentration of 1.3 mg/L was reported. The authors suggest that the relative infant dose would be about 0.2 mg/kg, or 6% of the maternal dose per day. 8 Hence, these studies all indicate that nitrofurantoin's relative infant dose is less than 10% of the maternal dose and is therefore compatible with breastfeeding.
The only potential concern in the infant is diarrhea, which was reported by 2 of 6 nursing mothers following nitrofurantoin use in a prospective follow-up study conducted by Motherisk. 9
There is a theoretical risk of hemolytic anemia in all newborns with exposure to nitrofurantoin owing to glutathione instability as a result of their immature erythrocyte enzyme systems. 2 Therefore, some have suggested that mothers exposed to nitrofurantoin should avoid breastfeeding infants younger than 1 month, 10,11 especially those infants with hyperbilirubinemia.11 This might be a conservative recommendation, as studies have shown that this phenomenon might be transient. 12-14 In a follow-up study of term infants, the glutathione instability had normalized by the eighth day of life. 15 In a serial estimation of glutathione stability in preterm infants, such a finding was also observed. 16 Nevertheless, a similar concern might also be valid among infants, regardless of age, with an absolute or relative glucose-6-phosphate dehydrogenase (G6PD) deficiency. 17 Such deficiencies are commonly observed in eastern Mediterranean (eg, in those of Sardinian, Italian, Greek, or Jewish ethnicity), African, and Southeast Asian populations. 18 However, there are no published case reports of hemolytic anemia in infants caused by exposure to nitrofurantoin in breast milk.
Although nitrofurantoin might be actively excreted into breast milk, it is present in low amounts, with a maximum relative infant dose documented in the literature of 6%.8 Some have suggested a theoretical risk of hemolytic anemia in infants younger than 1 month owing to glutathione instability. However, this appears to be a conservative view, as studies have reported normalization of this phenomenon by the eighth day of life in both term and preterm infants. Those with G6PD deficiencies, on the other hand, might be at risk regardless of age. Nevertheless, there have been no reported cases of complications in either at-risk group. If this is a concern for the patient or clinician, an alternative antibiotic might be prescribed. However, if the infant is older than 8 days and is unlikely to have a G6PD deficiency, then the use of nitrofurantoin might not be a reason to avoid
Motherisk questions are prepared by the Motherisk Team at The Hospital for Sick Children in Toronto, Ont. Ms. Zao is a doctoral candidate in the Faculty of Pharmacy at the University of Toronto. Dr. Koren is Director and Ms Bozzo is Assistant Director of the Motherisk Program. Dr Koren is supported by the Research Leadership for Better Pharmacotherapy during Pregnancy and Lactation. He holds the Ivey Chair in Molecular Toxicology in the Department of Medicine at the University of Western Ontario in London.
Do you have questions about the effects of drugs, chemicals, radiation, or infections in women who are pregnant or breastfeeding? We invite you to submit them to the Motherisk Program by fax at 416 813-7562; they will be addressed in future Motherisk Updates.
Published Motherisk Updates are available on the Canadian Family Physician website (www.cfp.ca) and also on the Motherisk website.
Copyright © the College of Family Physicians of Canada
Can Fam Physician
Vol. 60, No. 6, June 2014 539-540
June 2014 vol. 60 no. 6 539-540
Copyright © 2014 by The College of Family Physicians of Canada
- Leth RA, M?ller JK, Thomsen RW, Uldbjerg N, N?rgaard M. Risk of selected postpartum infections after cesarean section compared with vaginal birth: a five-year cohort study of 32,468 women. Acta Obstet Gynecol Scand 2009;88(9):976-83. Medline | Search Google Scholar
- Nitrofurantoin [product monograph]. Toronto, ON: Warner Chilcott Canada Co; 2010.
- Bennett PN, editor. Drugs and human lactation. 2nd ed. London, UK: Elsevier; 1996. Use of the monographs on drugs; p. 70-3. Search Google Scholar
- Merino G, Jonker JW, Wagenaar E, van Herwaarden AE, Schinkel AH. The breast cancer resistance protein (BCRP/ABCG2) affects pharmacokinetics, hepatobiliary excretion, and milk secretion of the antibiotic nitrofurantoin. Mol Pharmacol 2005;67(5):1758-64. Epub 2005 Feb 11. Abstract/FREE Full Text
- Hosbach RH, Foster RB. Absence of nitrofurantoin from human milk [letter]. JAMA 1967;202(11):1057. Medline | Search Google Scholar
- Varsano I, Fischl J, Shochet SB. The excretion of orally ingested nitrofurantoin in human milk. J Pediatr 1973;82(5):886-7. CrossRef | Medline | Search Google Scholar
- Pons G, Rey E, Richard MO, Vauzelle F, Francoual C, Moran C, et al. Nitrofurantoin excretion in human milk. Dev Pharmacol Ther 1990;14(3):148-52. Medline | Search Google Scholar
- Gerk PM, Kuhn RJ, Desai NS, McNamara PJ. Active transport of nitrofurantoin into human milk. Pharmacotherapy 2001;21(6):669-75. CrossRef | Medline | Search Google Scholar
- Ito S, Blajchman A, Stephenson M, Eliopoulos C, Koren G. Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medication. Am J Obstet Gynecol 1993;168(5):1393-9. CrossRef | Medline | Search Google Scholar
- Briggs GG, Freeman RK, Yaffe SJ, editors. Drugs in pregnancy and lactation. 9th ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2011. Nitrofurantoin; p. 1033-5.
- Hale TW, editor. Medications and mothers' milk. Amarillo, TX: Hale; 2012. Nitrofurantoin; p. 842-3.
- Gross RT, Hurwitz RE. The pentose phosphate pathway in human erythrocytes; relationship between the age of the subject and enzyme activity. Pediatrics 1958;22(3):453-60. Abstract/FREE Full Text
- Zinkham WH, Childs B. Effect of vitamin K and naphthalene metabolites on glutathione metabolism of erythrocytes from normal newborns and patients with naphthalene hemolytic anemia [abstract]. AMA Am J Dis Child 1957;94(6):708-11. CrossRef
- Zinkham WH. An in-vitro abnormality of glutathione metabolism in erythrocytes from normal newborns: mechanism and clinical significance. Pediatrics 1959;23(1 Pt 1):18-32. Abstract/FREE Full Text
- Szeinberg A, Ramot B, Sheba C, Adam A, Halbrecht I, Rikover M, et al. Glutathione metabolism in cord and newborn infant blood. J Clin Invest 1958;37(10):1436-41. Medline | Search Google Scholar
- Ghai OP, Khandpur SC, Sarin GS, Walia BN. Some observations on glutathione stability of erythrocytes in newborn period. Indian Pediatr 1964;1:215-8. Medline | Search Google Scholar
- Beutler E. G6PD: population genetics and clinical manifestations. Blood Rev 1996;10(1):45-52. CrossRef | Medline | Search Google Scholar
- Gait JE. Hemolytic reactions to nitrofurantoin in patients with glucose-6-phosphate dehydrogenase deficiency: theory and practice. DICP 1990;24(12):1210-3. Abstract/FREE Full Text