1 INDICATIONS AND USAGE BEPREVE® (bepotastine besilate ophthalmic solution) 1.5% is a histamine H1 receptor antagonist indicated for the treatment of itching associated with signs and symptoms of allergic conjunctivitis. BEPREVE ® is a histamine H1 receptor antagonist indicated for the treatment of itching associated with allergic conjunctivitis. (1)
3 DOSAGE FORMS AND STRENGTHS Topical ophthalmic solution containing bepotastine besilate 1.5%. Solution containing bepotastine besilate, 1.5%. (3)
4 CONTRAINDICATIONS Bepreve is contraindicated in patients with a history of hypersensitivity reactions to bepotastine or any of the other ingredients [see Adverse Reactions (6.2)].
5 WARNINGS AND PRECAUTIONS •To minimize the risk of contamination, do not touch dropper tip to any surface. Keep bottle tightly closed when not in use. (5.1) •BEPREVE should not be used to treat contact lens-related irritation. (5.2) •Remove contact lenses prior to instillation of BEPREVE. (5.2) 5.1 Contamination of Tip and Solution To minimize contaminating the dropper tip and solution, care should be taken not to touch the eyelids or surrounding areas with the dropper tip of the bottle. Keep bottle tightly closed when not in use. 5.2 Contact Lens Use Patients should be advised not to wear a contact lens if their eye is red. BEPREVE should not be used to treat contact lens-related irritation. BEPREVE should not be instilled while wearing contact lenses. Remove contact lenses prior to instillation of BEPREVE. The preservative in BEPREVE, benzalkonium chloride, may be absorbed by soft contact lenses. Lenses may be reinserted after 10 minutes following administration of BEPREVE. 5.3 Topical Ophthalmic Use Only BEPREVE is for topical ophthalmic use only.
6 ADVERSE REACTIONS The most common adverse reaction occurring in approximately 25% of patients was a mild taste following instillation. Other adverse reactions which occurred in 2-5% of subjects were eye irritation, headache, and nasopharyngitis. (6) To report SUSPECTED ADVERSE REACTIONS, contact Bausch & Lomb Incorporated. at 1-800-323-0000, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The most common reported adverse reaction occurring in approximately 25% of subjects was a mild taste following instillation. Other adverse reactions occurring in 2-5% of subjects were eye irritation, headache, and nasopharyngitis. 6.2 Post Marketing Experience Hypersensitivity reactions have been reported rarely during the post-marketing use of BEPREVE. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a casual relationship to drug exposure. The hypersensitivity reactions include itching, body rash, and swelling of lips, tongue and/or throat.
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C: Teratogenicity studies have been performed in animals. Bepotastine besilate was not found to be teratogenic in rats during organogenesis and fetal development at oral doses up to 200 mg/kg/day (representing a systemic concentration approximately 3,300 times that anticipated for topical ocular use in humans), but did show some potential for causing skeletal abnormalities at 1,000 mg/kg/day. There were no teratogenic effects seen in rabbits at oral doses up to 500 mg/kg/day given during organogenesis and fetal development (>13,000 times the dose in humans on a mg/kg basis). Evidence of infertility was seen in rats given oral bepotastine besilate 1,000 mg/kg/day; however, no evidence of infertility was observed in rats given 200 mg/kg/day (approximately 3,300 times the topical ocular use in humans). The concentration of radio-labeled bepotastine besilate was similar in fetal liver and maternal blood plasma following a single 3 mg/kg oral dose. The concentration in other fetal tissues was one-third to one-tenth the concentration in maternal blood plasma. An increase in stillborns and decreased growth and development were observed in pups born from rats given oral doses of 1,000 mg/kg/day during perinatal and lactation periods. There were no observed effects in rats treated with 100 mg/kg/day. There are no adequate and well-controlled studies of bepotastine besilate in pregnant women. Because animal reproduction studies are not always predictive of human response, BEPREVE® (bepotastine besilate ophthalmic solution) 1.5% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 8.3 Nursing Mothers Following a single 3 mg/kg oral dose of radiolabeled bepotastine besilate to nursing rats 11 days after delivery, the maximum concentration of radioactivity in milk was 0.40 mcg-eq/mL 1 hour after administration; at 48 hours after administration the concentration was below detection limits. The milk concentration was higher than the maternal blood plasma concentration at each time of measurement. It is not known if bepotastine besilate is excreted in human milk. Caution should be exercised when BEPREVE (bepotastine besilate ophthalmic solution) 1.5% is administered to a nursing woman. 8.4 Pediatric Use Safety and efficacy of BEPREVE (bepotastine besilate ophthalmic solution) 1.5% have not been established in pediatric patients under 2 years of age. Efficacy in pediatric patients under 10 years of age was extrapolated from clinical trials conducted in pediatric patients greater than 10 years of age and from adults. 8.5 Geriatric Use No overall difference in safety or effectiveness has been observed between elderly and younger patients.