May 27 2022




Recommendations

Risks to the infant

Several studies of few patients, with standard doses of metronidazole, have not detected changes in neonates. However, there have reported cases of candida infection and diarrhea after administration of metronidazole to the mother. Some data suggest that the presence of the fungus Candida albicans, both in the mouth and in the rectum is more common in children exposed to metronidazole through breastfeeding.

American Academy of Pediatrics recommends discontinue breastfeeding for 12-24 hours after administration of a single dose of 2 g metronidazole (STAT dose), to allow drug levels in milk to fall enough. A kinetic study has shown that the drug concentration in milk decreases from 45.8 mg/L at two hours after its administration until 12.6 mg/L at 18 hours after taking it.

Influence on lactation

In two studies with a small number of patients, in infants whose mothers received oral metronidazole 1200 mg a day in three doses, were recorded average levels of metronidazole and its hydroxy metabolite between 4 and 32% of the metronidazole concentration of the mother and between 8 and 96% of that of hydroxymetronidazole.

In a group of twelve women who received the standard dose of 400 mg metronidazole every eight hours, the concentration of the drug in milk decreased from 15.5 mg/L at two hours after the intake of metronidazole to 9.1 mg/L at eight hours. According to these data, a 5 kg baby exclusively breastfed receive approximately 7 to 11 mg/day of metronidazole through breastfeeding. A therapeutic dosage in the same child would need 50 to 100 mg of metronidazole per day. Some authors estimate that the dose received by the infant would not exceed 10% of therapeutics.

Recommendations

The final effect on the infant is unknown, but the baby breastfed by mothers receiving metronidazole by any route, including topical, must be controlled.

Metronidazole has shown to be potentially carcinogenic in animals, as well as genotoxic and mutagenic in bacteria, so metronidazole administration to the mother, even admitting its necessity, must be very well argued and could not exist better alternative. The issue is controversial and there is no an unanimous opinion. For some authors, metronidazole would be just the opposite. There is not any in-depth study on the subject.

References

1.American Academy of Pediatrics Committee on Drugs. The transfer of drugs and other chemicals into human milk. Pediatrics. 2001; 108:776-89.
2.Bendesky A, Menendez D, Ostrosky-Wegman P. Is metronidazole carcinogenic? Mutat Res. 2002; 511:133-44.
3.Bergan T, Leinebo O, Blom-Hagen T, Salvesen B. Pharmacokinetics and bioavailability of metronidazole after tablets, suppositories and intravenous administration. Scand J Gastroenterology Suppl.1984; 91: 45-60.
4.Bowes WA Jr. The effect of medications on the lactating mother and her infant. Clin Obstet Gynecol. 1980 Dec; 23(4):1073-80.
5.Clements CJ. Metronidazole and breast feeding. N Z Med J. 1980 Oct 22; 92(670):329.
6.Chung AM, Reed MD, Blumer JL. Antibiotics and breast-feeding: a critical review of the literature. Paediatr Drugs. 2002; 4:817-37.
7.Dobias L, Cerna M, Rossner P et al. Genotoxicity and carcinogenicity of metronidazole. Mutat Res. 1994; 317:177-94.
8.Erickson SH, Oppenheim GL, Smith GH. Metronidazole in breast milk. Obstet Gynecol. 1981; 57:48-50.
9.Heisterberg L, Branebjerg PE. Blood and milk concentrations of metronidazole in mothers and infants.J Perinat Med. 1983; 11(2): 114-20.
10.Passmore CM, McElnay JC, Rainey EA, D'Arcy PF. Metronidazole excretion in human milk and its effect on the suckling neonate. Br J Clin Pharmacol. 1988 Jul; 26(1): 45-51.
11.Roe FJ Toxicologic evaluation of metronidazole with particular reference to carcinogenic, mutagenic, and teratogenic potential. Surgery. 1983; 93(1 Pt 2): 158-64.
12.. An evaluation of metronidazole in the prophylaxis of anaerobic infections in obstetrical patients. J Antimicrob Chemother. 1978; 4:55-62.
13.Upadhyaya P, Bhatnagar V, Basu N. Pharmacokinetics of intravenous metronidazole in neonates. J Pediatr Surg. 1988 Mar; 23(3):263-5.
14.Van Oosten MA, Notten FJ, Mikx FH. Metronidazole concentrations in human plasma, saliva, and gingival crevice fluid after a single dose. J Dent Res. 1986 Dec; 65(12):1420-3.

Warning of the manufacturer:

Metronidazole is excreted in human milk and should therefore be avoided unnecessary administration of the drug during lactation.

Updated:13.04.08