Elestat Warnings, Precautions, Pregnancy, Nursing, Abuse - Epinastine

Elestat Warnings, Precautions, Pregnancy, Nursing, Abuse - Epinastine

WARNINGS

ELESTAT™ is for topical ophthalmic use only and not for injection or oral use.

Information for Patients: Patients should be advised not to wear a contact lens if their eye is red. ELESTAT™ should not be used to treat contact lens related irritation. The preservative in ELESTAT™, benzalkonium chloride, may be absorbed by soft contact lenses. Contact lenses should be removed prior to instillation of ELESTAT™ and may be reinserted after 10 minutes following its administration.

Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye, surrounding structures, fingers, or any other surface in order to avoid contamination of the solution by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.

Bottle should be kept tightly closed when not in use.

Carcinogenesis, Mutagenesis, Impairment of Fertility:
In 18-month or 2-year dietary carcinogenicity studies in mice or rats, respectively, epinastine was not carcinogenic at doses up to 40 mg/kg [approximately 30,000 times higher than the maximum recommended ocular human dose of 0.0014 mg/kg/day (MROHD) on a mg/kg basis, assuming 100% absorption in humans and animals].

Epinastine in newly synthesized batches was negative for mutagenicity in the Ames/Salmonella assay and in vitro chromosome aberration assay using human lymphocytes. Positive results were seen with early batches of epinastine in two in vitro chromosomal aberration studies conducted in 1980s with human peripheral lymphocytes and with V79 cells, respectively. Epinastine was negative in the in vivo clastogenicity studies, including the mouse micronucleus assay and chromosome aberration assay in Chinese hamsters. Epinastine was also negative in the cell transformation assay using Syrian hamster embryo cells, V79/HGPRT mammalian cell point mutation assay, and in vivo/in vitro unscheduled DNA synthesis assay using rat primary hepatocytes.

Epinastine had no effect on fertility of male rats. Decreased fertility in female rats was observed at an oral dose up to approximately 90,000 times the MROHD.

Pregnancy: Teratogenic Effects: Pregnancy Category C
In an embryofetal developmental study in pregnant rats, maternal toxicity with no embryofetal effects was observed at an oral dose that was approximately 150,000 times the MROHD. Total resorptions and abortion were observed in an embryofetal study in pregnant rabbits at an oral dose that was approximately 55,000 times the MROHD. In both studies, no drug-induced teratogenic effects were noted.

Epinastine reduced pup body weight gain following an oral dose to pregnant rats that was approximately 90,000 times the MROHD.

There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, ELESTAT™ ophthalmic solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: A study in lactating rats revealed excretion of epinastine in the breast milk. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when ELESTAT™ ophthalmic solution is administered to a nursing woman.

Pediatric Use: Safety and effectiveness in pediatric patients below the age of 3 years have not been established.

Geriatric Use: No overall differences in safety or effectiveness have been observed between elderly and younger patients.