8.1 Pregnancy
Risk Summary
There are no available human data for the use of BESIVANCE during pregnancy to inform any drug-associated risks; however, systemic exposure to besifloxacin from ocular administration is low [see Clinical Pharmacology (12.3)].
Oral administration of besifloxacin to pregnant rats during organogenesis or during the pre/postnatal period did not produce adverse embryofetal or offspring effects at clinically relevant systemic exposures [see Data].
Data
Animal Data
In an embryofetal development study in rats, the administration of besifloxacin at oral doses up to 1,000 mg/kg/day during organogenesis was not associated with visceral or skeletal malformations in rat fetuses, although this dose was associated with maternal toxicity (reduced body weight gain and food consumption) and maternal mortality. Increased post-implantation loss, decreased fetal body weights, and decreased fetal ossification were also observed. At this dose, the mean Cmax in the rat dams was approximately 20 mcg/mL, approximately 46,500 times the mean plasma concentrations measured in humans at the recommended human ophthalmic dose (RHOD). The No Observed Adverse Effect Level (NOAEL) for this embryofetal development study was 100 mg/kg/day (Cmax, 5 mcg/mL, approximately 11,600 times the mean plasma concentrations measured in humans at the RHOD).
In a prenatal and postnatal development study in rats, the NOAELs for both fetal/neonate and maternal toxicity were 100 mg/kg/day. At 1,000 mg/kg/day, pups weighed significantly less than controls and had a reduced neonatal survival rate. Attainment of developmental landmarks and sexual maturation was delayed, although surviving pups from this dose group that were reared to maturity did not demonstrate deficits in behavior, including activity, learning and memory, and their reproductive capacity appeared normal.
8.2 Lactation
Risk Summary
There are no data on the presence of BESIVANCE in human milk, the effects on the breastfed infant, or the effects on milk production. However, systemic exposure to besifloxacin following topical ocular administration is low [see Clinical Pharmacology (12.3)], and it is not known whether measurable levels of besifloxacin would be present in maternal milk following topical ocular administration.
The developmental and health benefits of breastfeeding should be considered, along with the mother s clinical need for BESIVANCE, and any potential adverse effects on the breastfed infant from BESIVANCE.
