Contraindications
4 CONTRAINDICATIONS Frovatriptan succinate tablets are contraindicated in patients with: • Ischemic coronary artery disease (CAD) (e.g., angina pectoris, history of myocardial infarction, or documented silent ischemia), or coronary artery vasospasm, including Prinzmetal’s angina [see Warnings and Precautions ( 5.1 )]. • Wolff-Parkinson-White Syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders [see Warnings and Precautions ( 5.2 )]. • History of stroke, transient ischemic attack (TIA), or history of hemiplegic or basilar migraine because these patients are at a higher risk of stroke [see Warnings and Precautions ( 5.4 )]. • Peripheral vascular disease [see Warnings and Precautions ( 5.5 )]. • Ischemic bowel disease [see Warnings and Precautions ( 5.5 )]. • Uncontrolled hypertension [see Warnings and Precautions ( 5.8 )]. • Recent use (i.e., within 24 hours) of another 5-HT 1 agonist, an ergotamine containing or ergot-type medication such as dihydroergotamine (DHE) or methysergide [see Drug Interactions ( 7.1 , 7.2 )]. • Hypersensitivity to frovatriptan succinate tablets (angioedema and anaphylaxis seen) [see Warnings and Precautions ( 5.9 )]. • History of coronary artery disease or coronary artery vasospasm ( 4 ) • Wolff-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders ( 4 ) • History of stroke, transient ischemic attack, or hemiplegic or basilar migraine ( 4 ) • Peripheral vascular disease ( 4 ) • Ischemic bowel disease ( 4 ) • Uncontrolled hypertension ( 4 ) • Recent (within 24 hours) use of treatment with another 5-HT 1 agonist, or an ergotamine-containing medication ( 4 ) • Hypersensitivity to frovatriptan succinate (angioedema and anaphylaxis seen) ( 4 )
Pregnancy & Breastfeeding
8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of frovatriptan in pregnant women. In animal studies, frovatriptan produced developmental toxicity (embryofetal lethality, fetal abnormalities, and decreased embryofetal growth) when administered to pregnant rats and rabbits at doses greater than those used clinically [see Animal Data] . In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The reported rate of major birth defects among deliveries to women with migraine ranged from 2.2% to 2.9% and the reported rate of miscarriage was 17%, which were similar to rates reported in women without migraine. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Published data have suggested that women with migraines may be at increased risk of preeclampsia during pregnancy. Data Animal Data When pregnant rats were administered frovatriptan (oral doses of 0, 100, 500, or 1000 mg/kg/day) throughout organogenesis, increased embryofetal mortality and an increased incidence of fetal malformations were observed at the high dose; decreased fetal body weights and increased incidences of fetal structural variations associated with growth impairment were observed at all doses. The lowest effect dose for embryofetal developmental toxicity in rats (100 mg/kg/day) is approximately 130 times the maximum recommended human dose (MRHD) of 7.5 mg/day on a body surface area (mg/m 2 ) basis. When pregnant rabbits were administered frovatriptan (oral doses of 0, 5, 20, or 80 mg/kg/day) throughout organogenesis, embryofetal mortality was increased at the mid and high doses. The no-effect dose for embryofetal developmental toxicity in rabbits (5 mg/kg/day) is approximately 13 times the MRHD on a mg/m 2 basis. Oral administration of frovatriptan (0, 100, 500, or 1000 mg/kg/day) to female rats t