Fetal Risk Summary
Montelukast, an oral inhibitor of the cysteinyl leukotriene CysLT1 receptor, is indicated for the prophylaxis and chronic treatment of asthma. Reproduction studies in rats and rabbits at doses up to 320 and 490 times the maximum recommended human daily oral dose (MRHOD) based on body surface area, respectively, found no evidence of teratogenicity (1). The drug impaired the fertility of female rats at 160 times, but not at 80 times, the MRHOD. Fertility in male rats was not affected by oral doses up to 650 times the MRHOD (1).
It is not known if montelukast crosses the human placenta. The molecular weight (about 608) is low enough, however, that transfer to the fetus should be expected. The drug crosses the placenta in rats and rabbits (1).
The manufacturer maintains a pregnancy registry for montelukast (2). As of May 2000, there were 66 prospective (reported before outcome of pregnancy known) reports of exposure during gestation. Of these, 36 of the pregnancy outcomes were pending, and 12 were lost to follow-up. Of the 18 remaining pregnancies, 14 were exposed in the 1st trimester, 1 was exposed in the 2nd trimester, 1 in the 3rd trimester, and the timing of two exposures was unknown. There were no pregnancy complications and all delivered healthy infants without congenital anomalies or newborn complications. Two of the liveborn infants were premature, 35 and 36 weeks’, respectively.
In six retrospective cases (received after pregnancy outcome was known), two terminated in spontaneous abortions at gestational weeks 8 and 5 or 6, respectively (2). No information on the embryos was available. Three normal liveborn infants were reported, one of whom had low birth weight. In another case, the mother died at 7 months’ gestation from severe asthma exacerbation but whether the fetus survived was not known. She had used montelukast for 4 weeks in the 2nd trimester.
During clinical trials, 38 women received montelukast with or without standard asthma therapy (b-adrenergic agents, corticosteroids, theophylline, and/or cromolyn sodium) (2). In all cases, montelukast treatment was limited to the 1st trimester. The outcome of three pregnancies was pending or lost to follow-up. The pregnancy of one woman, who was also receiving loratadine, an antihistamine, terminated in a 1st-trimester spontaneous abortion. In another, the report could not determine if her abortion was spontaneous or elective. Seven other women had spontaneous abortions in the 1st trimester, and nine pregnancies were electively terminated (none for identified medical indications). One fetal death at 2830 weeks’ gestation was attributed to preeclampsia, intraventricular cranial hemorrhage, immaturity, and placental infarcts (2). No congenital malformations were observed in the fetus by macroscopic analysis. Healthy, full-term infants were delivered from the remaining 16 pregnancies. No differences in the pregnancy outcomes were observed between the montelukast group and those who received placebo or beclomethasone (2).
In summary, montelukast is not teratogenic in animals, and there have been no reports of adverse pregnancy outcomes attributable to the drug in humans. However, the human data are very limited and lack sufficient power to detect an increased risk of congenital malformations or other adverse outcomes. One source states that montelukast may be safe to use during pregnancy, but this conclusion was based solely on animal studies (3). Health care providers are encouraged to report any prenatal exposure to montelukast to the Merck Pregnancy Registry for Singulair at (800) 986-8999.
Breast Feeding Summary
No reports describing the use of montelukast during human lactation have been located. The molecular weight (about 608) is low enough, however, that excretion into breast milk should be expected. The drug is excreted into the milk of lactating rats (1). The potential effects on a nursing infant from exposure to the drug in milk are unknown.
- Product information. Singulair. Merck, 2000.
- Merck Pregnancy Registry for Singulair (montelukast sodium). Second annual report on exposure during pregnancy covering the period from approval through May 20, 2000. October, 2000.
- Anonymous. Drugs for asthma. Med Lett Drugs Ther 2000;42:1924.