###  Risk Summary

There are no studies or available data on pretomanid use in pregnant women to inform any drug-associated risks. There are risks associated with active tuberculosis during pregnancy (see Clinical Considerations). When Pretomanid Tablets are administered in combination with bedaquiline and linezolid, the pregnancy information for bedaquiline and linezolid also applies to this combination regimen. Refer to the bedaquiline and linezolid prescribing information for more information on bedaquiline and linezolid associated risks of use during pregnancy. In animal reproduction studies, there was increased post-implantation loss in the presence of maternal toxicity (reduced bodyweight and feed consumption) with oral administration of pretomanid during organogenesis in rats at doses about 4 times the exposure at the recommended dose in humans. There were no adverse embryo fetal effects in rats or rabbits dosed with oral pretomanid during organogenesis at doses up to approximately 2 times the exposure in humans.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the United States general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively.

###  Clinical Considerations

#### Disease-Associated Maternal and/or Embryo/Fetal Risk 

Active tuberculosis in pregnancy is associated with adverse maternal and neonatal outcomes including maternal anemia, caesarean delivery, preterm birth, low birth weight, birth asphyxia, and perinatal infant death. 

###  Data

###  Animal Data

In animal reproduction studies, pregnant rats were dosed orally with pretomanid at 10, 30, and 100 mg/kg/day during organogenesis (gestational Days 7 through 17). Rats showed increased post-implantation loss in the presence of maternal toxicity (including reduced body weight and feed consumption) at 100 mg/kg/day, approximately 4 times the exposure in humans for a 200 mg dose on an AUC basis. There were no adverse embryofetal effects in rats dosed with oral pretomanid during organogenesis at doses up to approximately 2 times the exposure in humans. Pregnant rabbits were dosed orally with pretomanid during organogenesis (gestational Days 7 through 19) at 10, 30, and 60 mg/kg/day. No evidence of adverse developmental outcomes was observed when oral doses of pretomanid were administered to dams during organogenesis (gestational Days 7 to 19) at doses up to 60 mg/kg/day (approximately 2 times the exposure in humans for a 200 mg dose on an AUC basis).

In a pre- and postnatal development study, there were no adverse developmental effects in pups of pregnant rats orally dosed with up to 20 mg/kg/day from gestational Day 6 through lactation Day 20. Pups of pregnant females dosed at 60 mg/kg/day (about 2 times the exposure for the 200 mg dose) had lower body weights and a slight delay in the age at which the air-drop righting reflex developed. These effects occurred at a maternally toxic dose (based on maternal weight loss and reduced food consumption).