Alcaftadine

Risk Summary

There are no adequate and well-controlled studies with alcaftadine in pregnant women to inform a drug associated risk. There are limited data with the use of alcaftadine eye drops in pregnant women.

In embryofetal studies in rats and rabbits, oral administration of alcaftadine during the period of organogenesis did not produce maternal or embryofetal toxicity at clinically relevant doses.

Advise pregnant women of a potential risk to the fetus and mother. Alcaftadine should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus and mother. The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4%, and of miscarriage is 15 to 20%, of clinically recognized pregnancies.

Data

Animal Data

In rats, oral administration of 5, 20 or 40 mg/kg/day alcaftadine during the period of organogenesis (gestational days 6-16) caused maternal lethality at doses of 40 mg/kg. The no observed adverse effect level (NOAEL) for maternal toxicity was 20 mg/kg/day (an exposure 230-times higher than that at the maximum recommended human ophthalmic dose [MRHOD], based on AUC). There were no adverse embryofetal effects up to a dose of 20 mg/kg.

In rabbits, oral administration of 10, 40 or 80 mg/kg/day alcaftadine during the period of organogenesis (gestational days 6-18) caused no maternal toxicity or adverse embryofetal effects up to a dose of 80 mg/kg/day (an exposure 8819-times higher than that at the MRHOD, based on AUC).

Daily oral doses of 20 and 30 mg/kg/day alcaftadine administered to rats from Day 6 of pregnancy until Day 20 postpartum produced lower pup weights in offspring. No adverse effects in dams or offspring were observed at doses up to 5 mg/kg/day (a dose 286 times higher than the MRHOD, on a mg/m² basis).

Risk Summary

There is no information regarding the presence of alcaftadine in human milk, the effects on the breastfed infants, or the effects on milk production to inform risk of alcaftadine to an infant during lactation. The developmental and health benefits of breastfeeding should be considered, along with the mother’s clinical need for alcaftadine, and any potential adverse effects on the breastfed infant from alcaftadine.

Carcinogenesis

The carcinogenic potential of alcaftadine has not been evaluated in long-term animal studies.

Mutagenesis

Alcaftadine was not mutagenic or genotoxic in the Ames test, the mouse lymphoma assay or the mouse micronucleus assay.

Impairment of Fertility

Alcaftadine was found to have no effect on fertility of male and female rats at oral doses up to 20 mg/kg/day (an exposure 230-times higher than that at the MRHOD, based on AUC).

The following adverse reactions have been identified during post-approval use of alcaftadine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

These reactions include eye discharge, eye swelling, erythema of eyelid, eyelid edema, lacrimation increased, vision blurred, hypersensitivity reactions including swelling of the face or allergic dermatitis, and somnolence.