Breast-feeding and treatment with metronidazole./nA woman with endometritis has been breast-feeding

Fråga: Breast-feeding and treatment with metronidazole. A woman with endometritis has been breast-feeding a two-week-old infant for two weeks. She has been treated with a single infusion metronidazole 1.5 gx1 the first day and thereafter oral treatment for 10 days. Is there any risk of harmful effects on the newborn infant from breast-feeding during maternal metronidazole treatment?

Sammanfattning: Metronidazole is excreated into breast milk. The concentration of the drug in breast-fed infants has been estimated to approximately 15-20 per cent of the maternal plasma concentration. Although mutagenicity and carcinogenicity of metronidazole has been observed in test species, no harmful effects in breast-fed infants have been shown. However, long term treatment is not recommended due to sparse documentation. With a multiple-dose regimen consisting of divided oral doses of up to 1200 mg metronidazole daily during 7-10 days, abstention from breast-feeding is not compulsory; the amount ingested by the infant is acceptable. Premature infants are another group where abstention from breast-feeding during therapy and for 48 hours after the last dose is advisable. Therefore, the treatment must be judged against the severity of infection, the maturity of the infant, and the relative importance of breast-feeding for mother and child.

Svar: Questions concerning possible harmful effects on the breast-fed infant during metronidazole treatment of the mother have been dealt with earlier at the Drug Information Center at Huddinge Hospital (1,2,3). A renewed Medline search has also been done. The adequateness of breast-feeding during metronidazole treatment has been discussed on basis of experimental observations since the drug has shown mutagenicity and carcinogenicity in some test species (4).

Metronidazole is distributed into maternal milk with a maternal milk to plasma ratio equal to one. The mean infant plasma concentration is approximately 15-20 per cent of the maternal plasma concentration (4,5).

A few mild instant adverse reactions in breast-fed infants to metronidazole treated mothers have been seen. No harmful effects in breast-fed infants have been documented. Only one case of diarrhoea and secondary lactose intolerance in a breast-fed infant whose mother was receiving metronidazole has been described (6,4). The relationship between the drug and events in this case is however, unknown. The total number of infants that has been examined in studies is small, and there is no knowledge on long-term harmful effects of the drug. Long-term treatment is, therefore, not recommended.

With a multiple dosage regimen consisting of divided oral doses of up to 1200 mg daily during 7-10 days, the amount ingested by the infant has been judged as acceptable, and abstention from breast-feeding of a normal child is not compulsory (7,8).

The half-life of metronidazole has shown to be prolonged up to 75 hours in prematures less than 32 weeks gestation, 35 hours from 32-35 weeks gestation and 25 hours in infants 36-40 weeks gestation. In a 6-week-old infant, the half-life (8-10 hours) was similar to that seen in adults (9). Therefore, in premature infants it is advisable to abstent from breast-feeding during therapy and for 48 hours after the last dose because of the significantly reduced clearance in these neonates (9,10).