Antihistamine (Ophthalmic)
PREGNANCY RECOMMENDATION: No Human Data—Probably Compatible
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of epinastine in human pregnancy have been located. The animal reproduction data, even though the comparison to the human dose was based on body weight, suggest low risk. Although the absence of human pregnancy experience prevents a more complete assessment, the very low systemic bioavailability, and the human experience with other agents in the antihistamine class, suggests that there is little if any embryo or fetal risk from epinastine.
FETAL RISK SUMMARY
Epinastine, a topically active H1-receptor antagonist and inhibitor of histamine from mast cells, is indicated for the prevention of itching associated with allergic conjunctivitis. It is administered as a 0.05% ophthalmic solution. Systemic bioavailability is low with average maximum plasma concentrations of 0.04 ng/mL measured after one drop in each eye twice daily for 7 days. There was no accumulation in the plasma. Less than 10% of epinastine undergoes metabolism. Binding to plasma proteins (64%) is moderate, but the terminal plasma elimination half-life is prolonged (about 12 hours) (1).
Reproduction studies have been conducted in rats and rabbits. In pregnant rats, maternal toxicity with no embryo or fetal effects was observed with an oral dose that was about 150,000 times the maximum recommended ocular human dose based on body weight (MROHD). However, pup body weight gain was reduced at a dose that was about 90,000 times the MROHD. In pregnant rabbits, resorptions and abortion occurred at an oral dose that was about 55,000 times the MROHD (1).
Carcinogenicity studies in mice and rats were negative at doses up to 30,000 times the MROHD. Epinastine also was negative in multiple studies for mutagenic and clastogenic effects. There was no effect on fertility in male rats, but decreased fertility was noted in female rats at an oral dose of about 90,000 times the MROHD (1).
It is not known if epinastine crosses the human placenta. The molecular weight (about 250 for the free base), low metabolism, moderate plasma protein binding, and prolonged elimination half-life suggest that the antihistamine will cross the placenta. However, the low systemic bioavailability probably prevents clinically significant amounts of the drug from reaching the embryo and fetus.
BREASTFEEDING SUMMARY
No reports describing the use epinastine during human lactation have been located. The molecular weight (about 250 for the free base), low metabolism, moderate plasma protein binding (64%), and prolonged elimination half-life (about 12 hours) suggest that the antihistamine will be excreted into human breast milk. However, the low systemic bioavailability probably prevents clinically significant amounts of the drug from appearing in milk. Moreover, in general, antihistamines obtaining therapeutic systemic concentrations are classified as compatible with breastfeeding. Epinastine should be classified similarly.
Reference
1.Product information. Elestat. Inspire Pharmaceuticals, 2007.