Moxifloxacin (ophthalmic)

Drug-drug interaction studies have not been conducted with moxifloxacin ophthalmic solution. In vitro studies indicate that moxifloxacin does not inhibit CYP3A4, CYP2D6, CYP2C9, CYP2C19, or CYP1A2, indicating that moxifloxacin is unlikely to alter the pharmacokinetics of drugs metabolized by these cytochrome P450 isozymes.

8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies with moxifloxacin ophthalmic solution in pregnant women to inform any drug-associated risks. Oral administration of moxifloxacin to pregnant rats and monkeys and intravenously to pregnant rabbits during the period of organogenesis did not produce adverse maternal or fetal effects at clinically relevant doses. Oral administration of moxifloxacin to pregnant rats during late gestation through lactation did not produce adverse maternal, fetal or neonatal effects at clinically relevant doses (see Data).

Data Animal Data Embryo-fetal studies were conducted in pregnant rats administered with 20, 100, or 500 mg/kg/day moxifloxacin by oral gavage on Gestation Days 6 to 17, to target the period of organogenesis. Decreased fetal body weight and delayed skeletal development were observed at 500 mg/kg/day [277 times the human area under the curve (AUC) at the recommended human ophthalmic dose]. The No-Observed-Adverse-Effect-Level (NOAEL) for developmental toxicity was 100 mg/kg/day (30 times the human AUC at the recommended human ophthalmic dose).

Embryo-fetal studies were conducted in pregnant rabbits administered with 2, 6.5, or 20 mg/kg/day moxifloxacin by intravenous administration on Gestation Days 6 to 20, to target the period of organogenesis. Abortions, increased incidence of fetal malformations, delayed fetal skeletal ossification, and reduced placental and fetal body weights were observed at 20 mg/kg/ day (1086 times the human AUC at the recommended human ophthalmic dose), a dose that produced maternal body weight loss and death. The NOAEL for developmental toxicity was 6.5 mg/ kg/day (246 times the human AUC at the recommended human ophthalmic dose).

Pregnant cynomolgus monkeys were administered moxifloxacin at doses of 10, 30, or 100 mg/kg/day by intragastric intubation between Gestation Days 20 and 50, targeting the period of organogenesis. At the maternal toxic doses of ≥ 30 mg/kg/day, increased abortion, vomiting, and diarrhea were observed. Smaller fetuses/reduced fetal body weights were observed at 100 mg/kg/day (2864 times the human AUC at the recommended human ophthalmic dose). The NOAEL for fetal toxicity was 10 mg/kg/day (174 times the human AUC at the recommended human ophthalmic dose).

In a pre- and postnatal study, rats were administered moxifloxacin by oral gavage at doses of 20, 100, and 500 mg/kg/day from Gestation Day 6 until the end of lactation. Maternal death occurred during gestation at 500 mg/kg/day. Slight increases in the duration of pregnancy, reduced…