Frovatriptan
(Frovatriptan Succinate)Frovatriptan Prescribing Information
Frovatriptan succinate tablets are indicated for the acute treatment of migraine with or without aura in adults.
- 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.
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 × 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.
2.5 mg Tablets: White to off white, round, film coated tablets debossed with '2.5' on one side and 'ZNF' on other side.
- Pregnancy: Based on animal data, may cause fetal harm(
8.1 PregnancyRisk SummaryThere 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 ConsiderationsDisease-Associated Maternal and/or Embryo/Fetal RiskPublished data have suggested that women with migraines may be at increased risk of preeclampsia during pregnancy.
DataAnimal DataWhen 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/m2) 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/m2basis.
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/m2basis.
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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 Myocardial Ischemia, Myocardial Infarction, and Prinzmetal’s Angina
Frovatriptan succinate is contraindicated in patients with ischemic or vasospastic CAD. There have been rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within a few hours following administration of frovatriptan succinate. Some of these reactions occurred in patients without known CAD. Frovatriptan succinate may cause coronary artery vasospasm (Prinzmetal's angina), even in patients without a history of CAD.
Perform a cardiovascular evaluation in triptan-naïve patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving frovatriptan succinate. Do not administer frovatriptan succinate if there is evidence of CAD or coronary artery vasospasm
[see Contraindications (4)].For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administrating the first frovatriptan succinate dose in a medically-supervised setting and performing an electrocardiogram (ECG) immediately following frovatriptan succinate administration. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of frovatriptan succinate.)]. - Wolff-Parkinson-White Syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders[see Warnings and Precautions (5.2 Arrhythmias
Life-threatening disturbances of cardiac rhythm including ventricular tachycardia and ventricular fibrillation leading to death have been reported within a few hours following the administration of 5-HT1agonists. Discontinue frovatriptan succinate if these disturbances occur. Frovatriptan succinate is contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders
[see Contraindications (4)].)]. - 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 Cerebrovascular Events
Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with 5-HT1agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine, when they were not.
Before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with symptoms atypical of migraine, other potentially serious neurological conditions need to be excluded. Frovatriptan succinate is contraindicated in patients with a history of stroke or TIA
[see Contraindications (4)].)]. - Peripheral vascular disease[see Warnings and Precautions (5.5 Other Vasospasm Reactions
Frovatriptan succinate may cause non-coronary vasospastic reactions, such as peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction (presenting with abdominal pain and bloody diarrhea), splenic infarction, and Raynaud's syndrome. In patients who experience symptoms or signs suggestive of a vasospastic reaction following the use of any 5-HT1agonist, rule out a vasospastic reaction before using frovatriptan succinate
[see Contraindications (4)].Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT1agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT1agonists have not been clearly established.
)]. - Ischemic bowel disease[see Warnings and Precautions (5.5 Other Vasospasm Reactions
Frovatriptan succinate may cause non-coronary vasospastic reactions, such as peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction (presenting with abdominal pain and bloody diarrhea), splenic infarction, and Raynaud's syndrome. In patients who experience symptoms or signs suggestive of a vasospastic reaction following the use of any 5-HT1agonist, rule out a vasospastic reaction before using frovatriptan succinate
[see Contraindications (4)].Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT1agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT1agonists have not been clearly established.
)]. - Uncontrolled hypertension[see Warnings and Precautions (5.8 Increase in Blood Pressure
Significant elevation in blood pressure, including hypertensive crisis with acute impairment of organ systems, has been reported on rare occasions in patients treated with 5-HT1agonists, including patients without a history of hypertension. Monitor blood pressure in patients treated with frovatriptan succinate. Frovatriptan succinate is contraindicated in patients with uncontrolled hypertension
[see Contraindications (4)].)]. - 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 Ergot-containing DrugsErgot-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-HT1B/1DAgonistsBecause their vasospastic effects may be additive, co-administration of frovatriptan succinate and other 5-HT1agonists (e.g., triptans) within 24 hours of each other is contraindicated
[see Contraindications (4)].)]. - Hypersensitivity to frovatriptan succinate (angioedema and anaphylaxis seen)[see Warnings and Precautions (5.9 Hypersensitivity Reactions
There have been reports of reactions, including anaphylaxis and angioedema, in patients receiving frovatriptan succinate. Such reactions can be life threatening or fatal. In general, anaphylactic reactions to drugs are more likely to occur in individuals with a history of sensitivity to multiple allergens. Frovatriptan succinate tablet is contraindicated in patients with a history of hypersensitivity reaction to frovatriptan succinate
[see Contraindications (4)].)].
- Myocardial ischemia/infarction or Prinzmetal's angina: Perform cardiac evaluation in patients with multiple cardiovascular risk factors ()5.1 Myocardial Ischemia, Myocardial Infarction, and Prinzmetal’s Angina
Frovatriptan succinate is contraindicated in patients with ischemic or vasospastic CAD. There have been rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within a few hours following administration of frovatriptan succinate. Some of these reactions occurred in patients without known CAD. Frovatriptan succinate may cause coronary artery vasospasm (Prinzmetal's angina), even in patients without a history of CAD.
Perform a cardiovascular evaluation in triptan-naïve patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving frovatriptan succinate. Do not administer frovatriptan succinate if there is evidence of CAD or coronary artery vasospasm
[see Contraindications (4)].For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administrating the first frovatriptan succinate dose in a medically-supervised setting and performing an electrocardiogram (ECG) immediately following frovatriptan succinate administration. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of frovatriptan succinate. - Arrhythmias: Discontinue frovatriptan succinate if occurs ()5.2 Arrhythmias
Life-threatening disturbances of cardiac rhythm including ventricular tachycardia and ventricular fibrillation leading to death have been reported within a few hours following the administration of 5-HT1agonists. Discontinue frovatriptan succinate if these disturbances occur. Frovatriptan succinate is contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders
[see Contraindications (4)]. - Chest/throat/neck/jaw pain, tightness, pressure, or heaviness: Generally, not associated with myocardial ischemia; evaluate high risk patients for coronary artery disease ()5.3 Chest, Throat, Neck, and Jaw Pain/Tightness/Pressure
Sensations of pain, tightness, pressure, and heaviness have been reported in the chest, throat, neck, and jaw after treatment with frovatriptan succinate and are usually non-cardiac in origin. However, perform a cardiac evaluation if these patients are at high cardiac risk. The use of frovatriptan succinate is contraindicated in patients with CAD and those with Prinzmetal's angina
[see Contraindications (4)]. - Cerebral hemorrhage, subarachnoid hemorrhage, and stroke: Discontinue frovatriptan succinate if occurs ()5.4 Cerebrovascular Events
Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with 5-HT1agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine, when they were not.
Before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with symptoms atypical of migraine, other potentially serious neurological conditions need to be excluded. Frovatriptan succinate is contraindicated in patients with a history of stroke or TIA
[see Contraindications (4)]. - Gastrointestinal ischemic reactions and peripheral vasospastic reactions: Discontinue frovatriptan succinate if occurs ()5.5 Other Vasospasm Reactions
Frovatriptan succinate may cause non-coronary vasospastic reactions, such as peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction (presenting with abdominal pain and bloody diarrhea), splenic infarction, and Raynaud's syndrome. In patients who experience symptoms or signs suggestive of a vasospastic reaction following the use of any 5-HT1agonist, rule out a vasospastic reaction before using frovatriptan succinate
[see Contraindications (4)].Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT1agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT1agonists have not been clearly established.
- Medication overuse headache: Detoxification may be necessary ()5.6 Medication Overuse Headache
Overuse of acute migraine drugs (e.g., ergotamine, triptans, opioids, or combination of these drugs for 10 or more days per month) may lead to exacerbation of headache (medication overuse headache). Medication overuse headache may present as migraine-like daily headaches or as a marked increase in frequency of migraine attacks. Detoxification of patients, including withdrawal of the overused drugs, and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary.
- Serotonin syndrome: Discontinue frovatriptan succinate if occurs (,5.7 Serotonin Syndrome
Serotonin syndrome may occur with frovatriptan succinate, particularly during co-administration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and monoamine oxidase (MAO) inhibitors
[see Drug Interactions (7.3)].Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). The onset of symptoms usually occurs within minutes to hours of receiving a new or a greater dose of a serotonergic medication. Discontinue frovatriptan succinate if serotonin syndrome is suspected.)7.3 Selective Serotonin Reuptake Inhibitors / Serotonin Norepinephrine Reuptake Inhibitors and Serotonin SyndromeCases of serotonin syndrome have been reported during combined use of triptans and SSRIs, SNRIs, TCAs, and MAO inhibitors
[see Warnings and Precautions (5.7)].