Ophthalmic (Antihistamine)
PREGNANCY RECOMMENDATION: No Human Data—Probably Compatible
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of bepotastine in human pregnancy have been located. The animal data suggest low risk. The systemic bioavailability is very low from ocular use; in addition, H1-receptor antihistamines are considered low risk in pregnancy. Although human pregnancy experience is needed, the drug probably is compatible in pregnancy.
FETAL RISK SUMMARY
Bepotastine is a histamine H1-receptor antagonist and inhibitor of the release of histamine from mast cells. It is indicated for the treatment of itching associated with allergic conjunctivitis. The product is available as a 1.5% solution with each milliliter containing 15 mg of bepotastine besilate (equivalent to 10.7 mg of bepotastine). The systemic absorption is minimal. In healthy adults, one drop of solution in both eyes 4 times daily for 7 days produced a peak plasma concentration of 7.3 ng/mL 1–2 hours after instillation. The elimination half-life apparently has not been determined, but plasma levels were below the quantifiable limit (2 ng/mL) at 24 hours. Metabolism also is minimal as about 75%–90% is excreted unchanged in the urine. Plasma protein binding is moderate (about 55%) (1).
Reproduction studies have been conducted with oral doses in rats and rabbits. During organogenesis and fetal development in rats, doses up to about 3300 times the systemic concentrations anticipated for topical ocular use in humans (SCH) were not teratogenic. At a dose 5 times higher, there was potential for causing skeletal abnormalities. When this higher dose was given during the perinatal and lactation periods, an increase in stillbirths and decreased growth and development were observed in rat pups. The no-observed-effect level was about 1650 times the SCH. In rabbits during organogenesis and fetal development, doses >13,000 times the human dose based on body weight were not teratogenic (1).
Bepotastine did not significantly induce neoplasms in mice or rats in long-term studies. There also was no evidence of genotoxicity in multiple assays. There was a slight reduction in fertility index and surviving fetuses when a dose much higher than 3300 times the SCH was given to male and female rats. Infertility was not seen when the dose was lowered to 3300 times the SCH (1).
It is not known if bepotastine crosses the human placenta. The molecular weight (about 389 for free acid) and moderate plasma protein binding suggest that the drug will cross to the embryo–fetus. However, the minimal systemic bioavailability suggests that the exposure will be clinically insignificant.
BREASTFEEDING SUMMARY
No reports describing the use of bepotastine during human lactation have been located. The molecular weight (about 389 for free acid) and moderate plasma protein binding suggest that the drug will be excreted into breast milk. However, the minimal systemic bioavailability suggests that any exposure of a nursing infant will be clinically insignificant.
Reference
1.Product information. Bepreve. ISTA Pharmaceuticals, 2009.