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 )
AND PRECAUTIONS Myocardial ischemia/infarction or Prinzmetal’s angina: Perform cardiac evaluation in patients with multiple cardiovascular risk factors. ( 5.1 ) Arrhythmias: Discontinue frovatriptan succinate if occurs. ( 5.2 ) 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 ) Cerebral hemorrhage, subarachnoid hemorrhage, and stroke: Discontinue frovatriptan succinate if occurs ( 5.4 ) Gastrointestinal ischemic reactions and peripheral vasospastic reactions: Discontinue frovatriptan succinate if occurs. ( 5.5 ) Medication overuse headache: Detoxification may be necessary. ( 5.6 ) Serotonin syndrome: Discontinue frovatriptan succinate if occurs. ( 5.7 , 7.3 )
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 <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> . 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.
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-HT 1 agonists. 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 <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> .
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 <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> .
5.4 Cerebrovascular Events Cerebral hemorrhage, subarachnoid hemorrhage, stroke, and other cerebrovascular events have been reported in patients treated with 5-HT 1 agonists, 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 <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> .
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-HT 1 agonist, rule out a vasospastic reaction before using frovatriptan succinate <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> . Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT 1 agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT 1 agonists have not been clearly established.
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.
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 <span class="opacity-50 text-xs">[see Drug Interactions (7.3) ]</span> . 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.
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-HT 1 agonists, 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 <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> .
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 <span class="opacity-50 text-xs">[see Contraindications (4) ]</span> .