Mebendazole

Concomitant use of mebendazole and metronidazole should be avoided [see Warnings and Precautions (5.3) ] .

8.1 Pregnancy Risk Summary The available published literature on mebendazole use in pregnant women has not reported a clear association between mebendazole and a potential risk of major birth defects or miscarriages [see Data ]. There are risks to the mother and fetus associated with untreated helminthic infection during pregnancy [see Clinical Considerations ] .

In animal reproduction studies, adverse developmental effects (i.e., skeletal malformations, soft tissue malformations, decreased pup weight, embryolethality) were observed when mebendazole was administered to pregnant rats during the period of organogenesis at single oral doses as low as 10 mg/kg (approximately 0.2-fold the maximum recommended human dose (MRHD)). Maternal toxicity was present at the highest of these doses [see Data ]. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S.

general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risks Untreated soil-transmitted helminth infections in pregnancy are associated with adverse outcomes including maternal iron deficiency anemia, low birth weight, neonatal and maternal death. Data Human Data Several published studies, including prospective pregnancy registries, case-control, retrospective cohort, and randomized controlled studies, have reported no association between mebendazole use and a potential risk of major birth defects or miscarriage.

Overall, these studies did not identify a specific pattern or frequency of major birth defects with mebendazole use. However, these studies cannot definitely establish the absence of any mebendazole-associated risk because of methodological limitations, including recall bias, confounding factors and, in some cases, small sample size or exclusion of first trimester mebendazole exposures. Animal Data Embryo-fetal developmental toxicity studies in rats revealed no adverse effects on dams or their progeny at doses up to 2.5 mg/kg/day on gestation days 6–15 (the period of organogenesis). Dosing at ≥10 mg/kg/day resulted in a lowered body weight gain and a decreased pregnancy rate.

Maternal toxicity, including body weight loss in one animal and maternal death in 11 of 20 animals, was seen at 40 mg/kg/day. At 10 mg/kg/day, increased embryo-fetal resorption (100% were resorbed at…