Is rizatriptan (a triptan) teratogenic?

Is Rizatriptan Teratogenic?

Rizatriptan is not considered teratogenic based on available evidence, but should be avoided during pregnancy unless the potential benefit clearly justifies the risk, with paracetamol (acetaminophen) being the preferred first-line treatment for migraine in pregnancy. 1, 2

Evidence from Animal Studies

• Animal reproductive studies showed no teratogenic effects when pregnant rats and rabbits received rizatriptan during organogenesis at doses up to 100 mg/kg/day and 50 mg/kg/day respectively (maternal exposures approximately 15 times human exposure at maximum recommended daily dose). 2
• However, animal studies did demonstrate other developmental concerns including decreased birth weights, reduced pre- and post-weaning weight gain in offspring, increased neonatal mortality, and decreased learning capacity at higher doses (100-250 mg/kg/day), though these occurred without apparent maternal toxicity. 2

Human Pregnancy Data

• No evidence of teratogenicity has been detected in human studies for any triptan, including rizatriptan. 3
• A comprehensive review of 25 prospective pregnancy reports in the Merck Pregnancy Registry found no suggestion that rizatriptan treatment predisposes patients to spontaneous abortions or congenital anomalies, though the sample size was small. 4
• A large Norwegian cohort study of 69,929 pregnant women found no significant association between triptan therapy during the first trimester and major congenital malformations (adjusted OR: 1.0; 95% CI 0.7-1.2). 5
• The most comprehensive review of triptan safety in pregnancy concluded that available data are sufficient to rule out large increases in birth defects, though small increases cannot be definitively excluded. 6

FDA Classification and Official Guidance

• Rizatriptan is FDA Pregnancy Category C, meaning it should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. 2
• The American Academy of Neurology recommends that triptans, including rizatriptan, should be used only under strict specialist supervision during pregnancy due to limited safety data. 1, 7

Preferred Treatment Approach in Pregnancy

• Paracetamol (acetaminophen) should be used as first-line medication for acute migraine treatment in pregnancy despite relatively poor efficacy. 1
• NSAIDs can be used only during the second trimester. 1
• If triptan therapy is deemed necessary, sumatriptan has the most extensive safety data from post-marketing surveillance and should be considered the preferred triptan if one must be used. 1, 7

Important Caveats

• While preterm birth rates appear to be elevated with triptan use, this has not been consistently demonstrated across all studies. 3
• Second and third trimester triptan use was associated with increased risk of atonic uterus (adjusted OR: 1.4; 95% CI 1.1-1.8) and blood loss >500 mL during labor (adjusted OR: 1.3; 95% CI 1.1-1.5). 5
• Rizatriptan crosses the placenta, as demonstrated in toxicokinetic studies in both rats and rabbits. 2