For topical use only. Not for injection.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Levocabastine was not carcinogenic in male or female rats or
in male mice when administered in the diet for up to 24 months. In female mice,
levocabastine doses of 5,000 and 21,500 times the maximum recommended ocular
human use level resulted in an increased incidence of pituitary gland adenoma
and mammary gland adenocarcinoma possibly produced by increased prolactin
The clinical relevance of this finding is unknown with
regard to the interspecies differences in prolactin physiology and the very low
plasma concentrations of levocabastine following ocular administration.
Mutagenic potential was not demonstrated for levocabastine
when tested in Ames' Salmonella reversion test or in Escherichia coli,
Drosophila melanogaster, a mouse Dominant Lethal Assay or in rat
In reproduction studies in rats, levocabastine showed no
effects on fertility at oral doses of 20 mg/kg/day (8,300 times the maximum recommended
human ocular dose).
Teratogenic Effects - Pregnancy Category C
Levocabastine has been shown to be teratogenic (polydactyly)
in rats when given in doses 16,500 times the maximum recommended human ocular
dose. Teratogenicity (polydactyly, hydrocephaly, brachygnathia),
embryotoxicity, and maternal toxicity were observed in rats at 66,000 times the
maximum recommended ocular human dose. There are no adequate and
well-controlled studies in pregnant women. Levocabastine should be used during
pregnancy only if the potential benefit justifies the potential risk to the
Based on determinations of levocabastine in breast milk
after ophthalmic administration of the drug to one nursing woman, it was calculated
that the daily dose of levocabastine in the infant was about 0.5 μg.
Safety and effectiveness in pediatric patients below the age
of 12 have not been established.