Antimigraine
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 frovatriptan in human pregnancy have been located. The animal data suggest low risk, but an assessment of the actual risk cannot be determined until human pregnancy experience is available. Although a 2008 review of triptans in pregnancy found no evidence for teratogenicity, the data did suggest a possible increase in the rate of preterm birth (1).
FETAL RISK SUMMARY
Frovatriptan is an oral selective serotonin (5-hydroxytryptamine [5-HT]) receptor agonist that has high affinity for 5-HT1B and 5-HT1D receptors. The drug is closely related to almotriptan, eletriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan. It is indicated for the acute treatment of migraine with or without aura in adults. Protein binding is minimal (about 15%). Several metabolites have been identified, but only one has affinity, lower than frovatriptan, for the 5-HT1B/1D receptors. The mean terminal elimination half-life of frovatriptan is about 26 hours (2).
Reproduction studies have been conducted in rats and rabbits. In rats, frovatriptan was given during organogenesis at oral doses ranging from 130 to 1300 times the maximum recommended human dose based on BSA (MRHD). Dose-related increases were found in the incidences of dilated ureters, unilateral and bilateral pelvic cavitation, hydronephrosis, and hydroureters. The renal effects were thought to be consistent with a slight delay in fetal maturation. A no-effect dose for this toxicity was not established. Skeletal variations (incomplete ossification of the sternebrae, skull, and nasal bones) were observed at all doses. In pregnant rabbits, oral doses up to 210 times the MRHD during organogenesis revealed no effects on fetal development (2).
It is not known if frovatriptan or its less active metabolite crosses the human placenta to the fetus. The molecular weight of the parent compound (about 243 for the free base) is low enough that passage to the fetus should be expected. In addition, the minimal protein binding and prolonged elimination half-life suggest that the drug will be available for transfer at the maternal:fetal interface.
BREASTFEEDING SUMMARY
No reports describing the use of frovatriptan during human lactation have been located. The molecular weight (about 243 for the free base), low plasma protein binding (about 15%), and prolonged elimination half-life (about 26 hours) suggest that the drug will be excreted into breast milk. The effect of this exposure on a nursing infant is unknown, but using an antimigraine agent with a shorter half-life should be considered.
References
1.Soldin OP, Dahlin J, O’Mara DM. Triptans in pregnancy. Ther Drug Monit 2008;30:5–9.
2.Product information. Frova. Elan Biopharmaceuticals, 2004.