Metronidazole and breastfeeding
- November 1, 2015
Metronidazole is often indicated in infections affecting breastfeeding mothers, such as trichomoniasis, pelvic inflammatory disease and bacterial vaginosis. This bulletin reviews the safety of metronidazole in breastfeeding women.
Transfer into breast milk
- Nearly all drugs transfer into breast milk to some extent, with concentrations in milk usually following concentrations in maternal plasma.
- Metronidazole transfers into milk in relatively high amounts, with concentrations in milk only slightly lower than those in maternal plasma.
- To estimate infant exposure, the amount (dose) ingested via milk can be expressed as a percentage of the mother’s dose (both adjusted for respective body weights); known as the relative infant dose or weight adjusted maternal dose (WAMD). For drugs that are not overtly toxic, a WAMD < 10% suggests safety in breastfeeding full-term, healthy infants.
- The reported WAMD for metronidazole varies and ranges from 12% to 24%. This is above the usually accepted safety cut-off of 10%. However, it is pertinent to remember that metronidazole is used in neonates, infants and children. Further, breastfed infants are likely to receive < 3 mg/kg/day from a maternal dose of 1500 mg/day (in divided doses), which is less than the therapeutic doses used in infants and children (7.5-30 mg/kg/day).
- One study found a stat 2 g oral metronidazole dose resulted in a 3 month-old exclusively breastfed infant ingesting 25 mg of metronidazole over 48 hours. This reflects significant exposure for young infants (close to the therapeutic dose used in this age-group). With a 12-hour discontinuation of breastfeeding post-dose, the 48-hour infant dose was reduced to 10 mg.
- Intravenous administration produces similar maternal plasma and milk concentrations to equivalent oral doses (metronidazole has almost 100% oral bioavailability).
- The rectal, vaginal and topical routes produce significantly lower plasma (and hence expected milk) concentrations than oral or intravenous administration, due to poorer bioavailability.
Unwanted effects in the infant
Numerous studies have shown virtually no untoward effects in breastfed infants. There are isolated and unsubstantiated reports of diarrhoea and candidiasis. Historically there has been some suggestion that metronidazole may impart a bitter taste to milk (perhaps related to the relatively common adverse effect of a ‘metallic taste’ found with therapeutic use); however, this is not supported by published evidence.
Mutagenic and carcinogenic risks
Historically, the safety of metronidazole in breastfeeding has been controversial due to data from animal studies showing that metronidazole is potentially carcinogenic and mutagenic. However, there is no substantiative evidence of these effects in humans. Additionally, clinical experience, and the consensus of specialist opinion, is that there is no known established carcinogenic or mutagenic risk to breastfeeding infants whose mothers are receiving short-course treatment with metronidazole by any route.