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 almotriptan in human pregnancy have been located. The animal data are suggestive of 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
Almotriptan is an oral selective serotonin (5-hydroxytryptamine; 5-HT1B/1D) receptor agonist that has high affinity for 5-HT1B, 5-HT1D, and 5-HT1F receptors. The drug is closely related to eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan (see also Eletriptan, Frovatriptan, 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 35%). Almotriptan is metabolized to inactive metabolites, but about 40% is excreted unchanged in the urine. The mean elimination half-life is approximately 3–4 hours (2).
Reproduction studies have been conducted in rats and rabbits. Rats were given doses throughout organogenesis that produced maternal exposures up to about 958 times the human exposure from the maximum recommended daily dose (MRDD) of 25 mg based on AUC (MRDD-AUC). At the highest dose (958 times the MRDD-AUC), increased embryo deaths were observed. Doses >80 times the MRDD-AUC resulted in an increased incidence of fetal skeletal variations (decreased ossification). When almotriptan was administered to pregnant rats throughout gestation and lactation, a dose 160 times the MRDD based on BSA (MRDD-BSA) caused an increase in gestational length and a decrease in litter size and pup birth weight. The decreased pup weight persisted throughout lactation. The no-observed-effect-level (NOEL) was 40 times the MRDD-BSA. In pregnant rabbits, a dose 50 times the MRDD-BSA resulted in an increase in embryo deaths (2).
It is not known if almotriptan crosses the human placenta to the fetus. The molecular weight (about 336 for the free base) is low enough that passage to the fetus should be expected. In addition, the minimal plasma protein binding, incomplete metabolism, and moderate elimination half-life suggest that substantial amounts of the drug will be available for transfer at the maternal:fetal interface.
BREASTFEEDING SUMMARY
No reports describing the use of almotriptan during human lactation have been located. The molecular weight (about 336 for the free base) suggests that the drug will be excreted into breast milk. The effect of this exposure on a nursing infant is unknown.
References
1.Soldin OP, Dahlin J, O’Mara DM. Triptans in pregnancy. Ther Drug Monit 2008;30:5–9.
2.Product information. Axert. Ortho-McNeil Pharmaceutical, 2004.