ZILEUTON

Fetal Risk Summary

Zileuton, a specific inhibitor of the enzyme (5-lipoxygenase) that catalyzes the formation of leukotrienes (LTB4, LTC4, LTD4, and LTE4), from arachidonic acid, is given orally for the prophylaxis and chronic treatment of asthma.

Reproduction studies have been conducted in rats and rabbits (1). No effects on fertility were observed in male and female rats given oral doses approximately 8 and 18 times the systemic exposure (area under the concentration curve [AUC]) achieved at the maximum recommended human daily oral dose (MRHD), respectively. However, at doses 9 or more times the MRHD (AUC basis), a reduction in fetal implants was observed. At 4 or more times the MRHD (AUC basis), increases in gestation length and the number of stillbirths were noted. In addition, offspring of pregnant rats given 18 times the MRHD (AUC basis) had reduced body weight and increased skeletal variations. A decrease in rat pup survival and growth occurred at this same dose in perinatal and postnatal studies. In pregnant rabbits given oral doses equivalent to the MRHD (body surface area basis), 3 (2.5%) of 118 fetuses had cleft palates (1).

It is not known if zileuton crosses the human placenta to the fetus, but the molecular weight (about 236) is low enough that transfer should be expected. The drug and/or its metabolites cross the rat placenta (1).

No reports on the use of zileuton in human pregnancy have been found. One source, based solely on animal data, recommends that the drug be avoided during gestation (2).

Breast Feeding Summary

No reports describing the use of zileuton during human lactation have been located. The drug and/or its metabolites are excreted into rat milk (1). The molecular weight (about 236) is low enough that passage into human breast milk should be expected. The effects on a nursing infant from this exposure are unknown.

References

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