Fetal Risk Summary
Rizatriptan, an oral, selective 5-hydroxytryptamine1B/1D receptor agonist, is indicated for the treatment of acute migraine attacks with or without aura in adults.
Reproduction studies have been conducted in rats and rabbits (1). Female rats were treated before and during mating, and throughout gestation and lactation with doses that produced maternal plasma exposures 15 and 225 times, respectively, the exposure in humans from the maximum recommended human dose of 30 mg (MRHD). These doses were not maternally toxic, but did reduce birth weights, and pre- and post-weaning weight gain in offspring. The no-effect dose was approximately 1.5 times the MRHD. No teratogenic effects were observed in rats and rabbits given doses 225 and 115 times, respectively, the MRHD during organogenesis. Fetal weights were decreased at these doses, but maternal weight gain was also reduced. The no-effect doses were approximately 15 times the MRHD.
Rizatriptan crosses the placentas of rats and rabbits (1). The relatively low molecular weight of the free base (about 269) suggests that placental transfer of the drug will also occur in humans.
The Merck Pregnancy Registry program has data on 24 pregnancies exposed to rizatriptan (2). The outcome data for 19 of the pregnancies that were in clinical trials included 3 spontaneous abortions (SABs), 5 elective abortions (EAs), 1 patient lost to follow-up, and 11 liveborn infants (1 set of twins). Two liveborns (male twins) were delivered at 34 weeks’ gestation. In a comparison group of 11 pregnancies that were exposed to comparator drugs, placebo, or no medications, the outcomes were 2 SABs, 1 EA, 4 lost to follow-up, and 4 liveborn infants. Five pregnancies, four prospective and one retrospective, were enrolled in a postmarketing surveillance program. The outcomes in the prospective cases were one normal term live birth, one fetal death due to cord accident, and two outcomes pending. The retrospective report involved an infant with a de novo (i.e., spontaneous occurrence) duplication of chromosome 2 that was thought to be related to advanced maternal age. Although no adverse outcomes were observed in liveborn offspring, the limited number of exposures studied are not sufficient to detect a risk of rare disorders such as birth defects (2). Health care providers are encouraged to report prenatal exposures to rizatriptan by calling (800) 9868999.
Breast Feeding Summary
No reports describing the use of rizatriptan in human lactation have been located. The relatively low molecular weight of the free base (about 269) suggests that the drug will be excreted into breast milk. The effects of this exposure on a nursing infant are unknown.
- Product information. Maxalt. Merck, 2001.
- Second Annual Report from the Merck Pregnancy Registry for Maxalt (rizatriptan benzoate). October, 2000.