Use in Pregnancy: Risk Summary: There are limited amount of data from the use of Vigadexa in pregnant women. Prolonged or repeated systemic corticoid use during pregnancy has been associated with an increased risk of intra-uterine growth retardation. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy should be observed carefully for signs of hypoadrenalism.
Studies in rats, rabbits and monkeys with systemic moxifloxacin showed reproductive toxicity at exposure levels greater than 25-fold compared to the human AUC at the recommended therapeutic dose. Reproductive toxicity was also seen in animal studies with dexamethasone, both after systemic and ocular administration at therapeutic dose levels.
Vigadexa is not recommended during pregnancy.
Animal data: In rats, oral moxifloxacin was not teratogenic up to the dose of 500 mg/kg/d. Decreased fetal body weight and delayed skeletal development were observed at 500 mg/kg/d. No-observed-adverse-effect-level (NOAEL) for developmental toxicity was 100 mg/kg/d. This results in a safety margin of about 30-fold compared to the human AUC at the recommended therapeutic dose.
In rabbits, two studies were performed using intravenous administration of moxifloxacin. Increased fetal malformations, abortions, maternal death as well as reduced placental and fetal weights were observed at 20 mg/kg/d. The NOAEL for developmental toxicity was determined to be 6.5 mg/kg/d, leading to a safety margin of about 245-fold compared to the human AUC at the recommended therapeutic dose.
In cynomolgus monkeys, moxifloxacin was administered by intragastric instillation from gestation day 20 to 50. At the maternal toxic doses of 30 and 100 mg/kg/d, increased abortion, vomiting and diarrhea were observed. Fetal body weights were reduced at 100 mg/kg/d. NOAEL for fetal toxicity was 10 mg/kg/d, providing a safety margin of about 174-fold compared to the human AUC at the recommended therapeutic dose.
In a peri- and postnatal development study in rats with moxifloxacin, maternal toxicity was seen at doses of 20 mg/kg/d and above. Decreased litter size (prenatal loss and pup mortality) and fetotoxicity (reduced body weight) were observed at 500 mg/kg/d. The NOAEL for pre- and postnatal development until weaning (F1) was determined to be 100 mg/kg/d.
In embryo fetal development studies with dexamethasone in mice, rats and rabbits, a number of malformations were seen at maternal toxic doses following systemic administration. Dexamethasone has also been shown to be teratogenic in mice and rabbits following topical ophthalmic application. The overall NOAEL for developmental toxicity was derived from an (oral) rat study and was based on embryotoxicity (0.01 mg/kg/d). This results in a dose ratio of about 0.24 (based on body surface area) compared to the recommended human ocular dose of 6.6 μg/kg/d.
Use in Lactation: Risk summary: It is unknown whether moxifloxacin and dexamethasone are excreted in human breast milk. Animal studies have shown excretion of low moxifloxacin levels in breast milk after oral administration. Although it is not likely that the amount of moxifloxacin and dexamethasone would be detectable in human milk or be capable of producing clinical effects in the infant following maternal use of the product, a risk to the breastfed child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.