Frovatriptan

Product Type: HUMAN PRESCRIPTION DRUG

Route: ORAL

Dosage Form:

NDC: 69238-1539

Application: ANDA211292

Effective: 20190930

1 INDICATIONS AND USAGE Frovatriptan succinate tablets are indicated for the acute treatment of migraine with or without aura in adults. Limitations of Use Use only if a clear diagnosis of migraine has been established. If a patient has no response for the first migraine attack treated with frovatriptan succinate tablets, reconsider the diagnosis of migraine before frovatriptan succinate tablets are administered to treat any subsequent attacks. Frovatriptan succinate tablets are not indicated for the prevention of migraine attacks. Safety and effectiveness of frovatriptan succinate tablets have not been established for cluster headache. Frovatriptan succinate is a serotonin (5-HT 1B / 1D ) receptor agonist (triptan) indicated for the acute treatment of migraine with or without aura in adults. ( 1 ) Limitations of Use Use only after a clear diagnosis of migraine has been established. ( 1 ) Not indicated for the prophylactic therapy of migraine. ( 1 ) Not indicated for the treatment of cluster headache. ( 1 )

2 DOSAGE AND ADMINISTRATION Dosing Information The recommended dose is a single tablet of frovatriptan succinate (frovatriptan 2.5 mg) taken orally with fluids. If the migraine recurs after initial relief, a second tablet may be taken, providing there is an interval of at least 2 hours between doses. The total daily dose of frovatriptan succinate tablets should not exceed 3 tablets (3 x 2.5 mg per 24-hour period). There is no evidence that a second dose of frovatriptan succinate tablets are effective in patients who do not respond to a first dose of the drug for the same headache. The safety of treating an average of more than 4 migraine attacks in a 30-day period has not been established. 1 tablet taken with fluids. Second tablet may be taken 2 hours after initial dose if headache recurs following initial relief. Total dose not to exceed 3 tablets in any 24-hour period. ( 2 )

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 (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)

Not available.

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in other sections of the labeling: Myocardial Ischemia, Myocardial Infarction, and Prinzmetal’s Angina [see Warnings and Precautions (5.1) ] Arrhythmias [see Warnings and Precautions (5.2) ] Chest, Throat, Neck, and/or Jaw Pain/Tightness/Pressure [see Warnings and Precautions (5.3) ] Cerebrovascular Events [see Warnings and Precautions (5.4) ] Other Vasospasm Reactions [see Warnings and Precautions (5.5) ] Medication Overuse Headache [see Warnings and Precautions (5.6) ] Serotonin Syndrome [see Warnings and Precautions (5.7) ] Increases in Blood Pressure [see Warnings and Precautions (5.8) ] Hypersensitivity Reactions [see Contraindications (4) and Warnings and Precautions (5.8) ] Most common adverse reactions (≥ 2% and > placebo) were dizziness, headache, paresthesia, dry mouth, dyspepsia, fatigue, hot or cold sensation, chest pain, skeletal pain, and flushing. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Frovatriptan succinate was evaluated in four randomized, double-blind, placebo-controlled, short-term trials. These trials involved 2,392 patients (1,554 on frovatriptan 2.5 mg and 838 on placebo). In these short-term trials, patients were predominately female (88%) and Caucasian (94%) with a mean age of 42 years (range 18 to 69). The treatment-emergent adverse events that occurred most frequently following administration of frovatriptan 2.5 mg (i.e . in at least 2% of patients), and at an incidence > 1% greater than with placebo, were dizziness, paresthesia, headache, dry mouth, fatigue, flushing, hot or cold sensation, dyspepsia, skeletal pain, and chest pain. In a long-term, open-label study where 496 patients were allowed to treat multiple migraine attacks with frovatriptan 2.5 mg for up to 1 year, 5% of patients (n=26) discontinued due to treatment-emergent adverse events. Table 1 lists treatment-emergent adverse events reported within 48 hours of drug administration that occurred with frovatriptan 2.5 mg at an incidence of > 2% and more often than on placebo, in the four placebo-controlled trials. The events cited reflect experience gained under closely monitored conditions of clinical trials in a highly selected patient population. In actual clinical practice or in other clinical trials, these incidence estimates may not apply, as the conditions of use, reporting behavior, and the kinds of patients treated may differ. T a ble 1: Adverse Reactions Reported within 48 Hours (Incidence > 2% and Greater Than Placebo) of Patients in Four Pooled Placebo-Controlled Migraine Trials Adverse Reactions Frovatriptan 2 .5 mg (n=1,554) Placebo (n=838) C entral & peripheral nervous system Dizziness Headache Paresthesia 8% 4% 4% 5% 3% 2% Gastrointestinal system disorders Dry mouth Dyspepsia 3% 2% 1% 1% Body as a whole – general disorders Fatigue Hot or cold sensation Chest pain 5% 3% 2% 2% 2% 1% Musculo-skeletal Skeletal pain 3% 2% Vascular Flushing 4% 2% The incidence of adverse events in clinical trials did not increase when up to 3 doses were used within 24 hours. The incidence of adverse events in placebo-controlled clinical trials was not affected by gender, age, or concomitant medications commonly used by migraine patients. There were insufficient data to assess the impact of race on the incidence of adverse events. Other Events Observed in Association with the Administration of frovatriptan succinate The incidence of frequently reported adverse events in four placebo-controlled trials is presented below. Events are further classified within body system categories. Frequent adverse events are those occurring in at least 1/100 patients. C entral and peripheral nervous system: dysesthesia and hypoesthesia. Gastrointestinal: vomiting, abdominal pain and diarrhea. Body as a whole: pain. Psychiatric: insomnia and anxiety. Respiratory: sinusitis and rhinitis. Vision disorders: vision abnormal. S kin and appendages: sweating increased. Hearing and vestibular disorders: tinnitus. Heart rate and rhythm: palpitation. 6.2 Postmarketing Experience The following adverse reactions were identified during post approval use of frovatriptan succinate. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. C entral and peripheral nervous system: Seizure.