Antihistamine
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of levocetirizine in human pregnancy have been located. The animal reproduction data suggest low risk, but the absence of human pregnancy experience prevents a more complete assessment of the embryo–fetal risk. There are no data suggesting that antihistamines, in general, are associated with human developmental toxicity, and the embryo–fetal risk from exposure levocetirizine appears to be low, if it exists at all. Nevertheless, if an antihistamine is required during pregnancy, agents with human pregnancy experience, such as chlorpheniramine or diphenhydramine, appear to be a better choice.
FETAL RISK SUMMARY
The antihistamine levocetirizine is a H1-receptor antagonist. It is the (R)-enantiomer and principal pharmacologically active component of the racemic compound cetirizine. (See also Cetirizine.) Levocetirizine is indicated for the relief of symptoms associated with allergic rhinitis (seasonal and perennial) and, for the treatment of uncomplicated skin manifestations of chronic idiopathic urticaria, both indications in adults and children 6 years of age or older. The drug is only partially metabolized (<14%) but plasma protein binding is high (91%–92%). The plasma half-life is about 8–9 hours (1,2).
Reproduction studies have been conducted in pregnant rats and rabbits. In these species, oral doses up to 320 and 390 times, respectively, the maximum recommended daily dose in adults based on BSA (MRDD), were not teratogenic (1,2).
Although carcinogenicity studies have not been conducted with levocetirizine, they have been with cetirizine. This drug was not carcinogenic in 2-year studies in rats. In a similar study in mice, cetirizine caused an increased incidence of benign hepatic tumors in males. Levocetirizine was not mutagenic or clastogenic in multiple assays. The antihistamine had no effect on fertility and general reproductive performance in mice at a dose that was about 25 times the MRDD (1,2).
It is not known if levocetirizine crosses the human placenta. The molecular weight (about 390 for the free base), minimum metabolism, and long plasma half-life suggest that the drug will reach the embryo–fetus, but the high plasma protein binding might lessen the amount crossing the placenta.
BREASTFEEDING SUMMARY
No reports describing the use of levocetirizine during human lactation have been located. The molecular weight (about 390 for the free base), minimum metabolism, and long plasma half-life suggest that the drug will be excreted into breast milk, but the high plasma protein binding might lessen the amount excreted. The effects of this exposure on a nursing infant are unknown, but sedation or irritability is a potential minor adverse effect.
Antihistamines are a large pharmacologic class of drugs, only one of which, when used alone, has been associated with major toxicity in a nursing infant. (See Clemastine.) Milk concentrations have been determined for only four antihistamines (see Fexofenadine, Loratadine, Terfenadine, and Triprolidine), and these four agents are considered compatible with breastfeeding by the American Academy of Pediatrics. The theoretical infant dose, as a percentage of the mother’s weight-adjusted dose, was calculated for three of drugs and was ≤0.45%. Because there is no reason to believe that levocetirizine should be any different, the drug probably is compatible with breastfeeding.
References
1.Product information. Xyzal. UCB, 2008.
2.Product information. Xyzal. Sanofi-Aventis, 2008.