Frovatriptan

7 DRUG INTERACTIONS

7.1 Ergot-containing Drugs Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and frovatriptan succinate within 24 hours of each other is contraindicated [ see Contraindications (4) ]. 7.2 5-HT 1B/1D Agonists Because their vasospastic effects may be additive, co-administration of frovatriptan succinate and other 5-HT 1 agonists (e.g., triptans) within 24 hours of each other is contraindicated [ see Contraindications (4) ].

7.3 Selective Serotonin Reuptake Inhibitors / Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome Cases of serotonin syndrome have been reported during combined use of triptans and SSRIs, SNRIs, TCAs, and MAO inhibitors [ see Warnings and Precautions (5.7) ].

7.1 Ergot-containing Drugs Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and frovatriptan succinate within 24 hours of each other is contraindicated [ see Contraindications (4) ]. 7.2 5-HT 1B/1D Agonists Because their vasospastic effects may be additive, co-administration of frovatriptan succinate and other 5-HT 1 agonists (e.g., triptans) within 24 hours of each other is contraindicated [ see Contraindications (4) ].

7.3 Selective Serotonin Reuptake Inhibitors / Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome Cases of serotonin syndrome have been reported during combined use of triptans and SSRIs, SNRIs, TCAs, and MAO inhibitors [ see Warnings and Precautions (5.7) ].

8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of frovatriptan succinate 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 throughout pregnancy and lactation resulted in increased embryofetal mortality at the high dose. The no effect dose for pre- and postnatal developmental toxicity in rats (500 mg/kg/day) is approximately 650 times the MRHD on a mg/m 2 basis.