Antibiotic
PREGNANCY RECOMMENDATION: No Human Data—Probably Compatible
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of retapamulin in human pregnancy have been located. The animal reproduction data are not relevant because, although there was developmental toxicity (death and restricted weight), these effects occurred with maternal toxicity. The absence of human pregnancy experience prevents a complete assessment of the embryo–fetal risk. However, the very low plasma concentrations suggest that there is little or no risk when the antibiotic is used topically in pregnancy.
FETAL RISK SUMMARY
Retapamulin is a semisynthetic pleuromutilin antibiotic that is available as a 1% ointment. The antibiotic is isolated through fermentation from Clitopilus passeckerianus (formerly Pleurotus passeckerianus). It is indicated for the topical treatment of impetigo due to Staphylococcus aureus (methicillin-susceptible isolates only) or Streptococcus pyogenes. Small amounts of retapamulin are absorbed into the systemic circulation.
In 380 adult and 136 pediatric (age 2–17 years) patients undergoing treatment with twice daily applications, 11% had measurable plasma concentrations (lower limit of quantitation 0.5 ng/mL), of which the median concentration was 0.8 ng/mL. The maximum measured concentrations in adult and pediatric patients were 10.7 and 18.5 ng/mL, respectively. The antibiotic is about 94% bound to plasma proteins, but the elimination half-life has not been determined due to the very low plasma concentrations. Retapamulin is metabolized by the liver to numerous metabolites (1).
Reproduction studies have been conducted in rats and rabbits. In rats, oral doses of ≥150 mg/kg/day (relationship to the human exposure not stated) caused maternal toxicity (decreased body weight and food consumption), decreased fetal weight, and delayed skeletal ossification. No treatment-related malformations were observed in the offspring. In rabbits, continuous IV infusions with doses producing exposures that were 8 times the estimated maximum achievable human exposure based on AUC were associated with maternal toxicity (decreased body weight and food consumption) and abortions. There were no other treatment-related effects on embryo–fetal development (1).
Carcinogenicity studies have not been conducted with retapamulin, but the drug was not genotoxic in multiple assays. No effects on fertility were noted in male and female rats given oral doses up to 450 mg/kg/day (1).
It is not known if retapamulin crosses the human placenta. The molecular weight (about 518) is low enough, but the very low plasma concentrations suggest that clinically significant exposure of the embryo and/or fetus is unlikely.
BREASTFEEDING SUMMARY
No reports describing the use of retapamulin during human lactation have been located. The molecular weight (about 518) is low enough for excretion into breast milk, but the very low plasma concentrations suggest that clinically significant exposure of a nursing infant is unlikely. Use of the antibiotic during breastfeeding probably is safe.
Reference
1.Product information. Altabax. GlaxcoSmithKline, 2007.