ZAFIRLUKAST

Fetal Risk Summary

Zafirlukast is an oral selective peptide leukotriene receptor antagonist that is indicated for the prophylaxis and chronic treatment of asthma. Reproduction studies conducted in mice, rats, and monkeys with oral doses up to 160, 400, and 800 times the maximum recommended human oral dose based on body surface area, respectively, did not observe any evidence of impaired fertility (only rats tested) or teratogenicity (1). The maximum doses in rats and monkeys were maternal toxic, resulting in maternal deaths in some cases, fetal resorptions (rats), and spontaneous abortions (monkeys).

It is not known if zafirlukast crosses the human placenta. The molecular weight (about 576) is low enough, however, that passage to the fetus should be expected.

No reports describing the use of zafirlukast during human pregnancy have been located. One source states that zafirlukast may be safe to use during pregnancy, but this conclusion is based solely on animal studies (2).

Breast Feeding Summary

The manufacturer reports that zafirlukast is excreted into human breast milk (1). In healthy women taking 40 mg orally twice daily, the average steady-state concentration of zafirlukast in milk was 50 ng/mL compared with 255 ng/mL in the plasma (milk:plasma ratio 0.2). The effects in a nursing infant from exposure to the drug in milk are unknown. However, the manufacturer recommends against breast-feeding because of the potential for tumorigenicity noted in mice and rats, and the enhanced sensitivity to the adverse effects of the drug in neonatal rats and dogs (1).

References

1. Product information. Accolate. AstraZeneca, 2000.
2. Anonymous. Drugs for asthma. Med Lett Drugs Ther 2000;42:19–24.