se of TOSYMRA was allowed over the course of 6 months. In this study, localirritative symptoms were reported in approximately 46% of patients treated with TOSYMRA,the most common of which were application site reactions (e.g., burning sensations in the nose),dysgeusia, and throat irritation [see Warnings and Precautions (5.11)].
6.2 Postmarketing Experience
The following adverse reactions have been identified during postapproval use of sumatriptantablets, sumatriptan nasal spray, and sumatriptan injection. Because these reactions are reportedvoluntarily from a population of uncertain size, it is not always possible to reliably estimate theirfrequency or establish a causal relationship to drug exposure.
Cardiovascular:
Hypotension, palpitations.
Neurological:
Dystonia, tremor.
7 DRUG INTERACTIONS
7.1 Ergot-Containing Drugs
Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Becausethese effects may be additive, use of ergotamine-containing or ergot-type medications (likedihydroergotamine or methysergide) and TOSYMRA within 24 hours of each other iscontraindicated.
7.2 Monoamine Oxidase-A Inhibitors
MAO-A inhibitors increase systemic exposure by 2-fold. Therefore, the use of TOSYMRA inpatients receiving MAO-A inhibitors is contraindicated [see Clinical Pharmacology (12.3)].
7.3 Other 5-HT1 Agonists
Because their vasospastic effects may be additive, coadministration of TOSYMRA and other 5HT1 agonists (e.g., triptans) within 24 hours of each other is contraindicated.
7.4 Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine
Reuptake Inhibitors and Serotonin SyndromeCases of serotonin syndrome have been reported during co-administration of triptans and SSRIs,SNRIs, TCAs, and MAO inhibitors [see Warnings and Precautions (5.7)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Data from a prospective pregnancy exposure registry and epidemiological studies of pregnantwomen have not detected an increased frequency of birth defects or a consistent pattern of birthdefects among women exposed to sumatriptan compared with the general population (see Data).
In developmental toxicity studies in rats and rabbits, oral administration of sumatriptan topregnant animals was associated with embryolethality, fetal abnormalities, and pup mortality.
When administered by the intravenous route to pregnant rabbits, sumatriptan was embryolethal(see Data).
In the U.S. general population, the estimated background risk of major birth defects and ofmiscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Thereported 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 inwomen without migraine.
Clinical Considerations
Disease-Associated Maternal and/or Embryo/Fetal Risk: Several studies have suggested thatwomen with migraine may be at increased risk of preeclampsia during pregnancy.
Data Human Data The Sumatriptan/Naratriptan/Treximet (sumatriptan and naproxen sodium) Pregnancy Registry,a population-based international prospective study, collected data for sumatriptan from January1996 to September 2012. The Registry documented outcomes of 626 infants and fetusesexposed to sumatriptan during pregnancy (528 with earlieste
