warnings and cautions
5 WARNINGS AND PRECAUTIONS Myocardial ischemia/infarction and Prinzmetal’s angina: Perform cardiac evaluation in patients with multiple cardiovascular risk factors. ( 5.1 ) Arrhythmias: Discontinue Sumavel DosePro if occurs. ( 5.2 ) Chest/throat/neck/jaw pain, tightness, pressure, or heaviness: Generally not associated with myocardial ischemia; evaluate for coronary artery disease in patients at high risk. ( 5.3 ) Cerebral hemorrhage, subarachnoid hemorrhage, or stroke: Discontinue Sumavel DosePro if occurs. ( 5.4 ) Gastrointestinal ischemia or infarction events, or peripheral vasospastic reactions: Discontinue Sumavel DosePro if occurs. ( 5.5 ) Medication overuse headache: Detoxification may be necessary. ( 5.6 ) Serotonin syndrome: Discontinue Sumavel DosePro if occurs. ( 5.7 ) Seizures: Use with caution in patients with epilepsy or a lowered seizure threshold. ( 5.10 ) 5.1 Myocardial Ischemia, Myocardial Infarction, and Prinzmetal’s Angina Sumavel DosePro 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 Sumavel DosePro. Some of these reactions occurred in patients without known CAD. Sumavel DosePro may cause coronary artery vasospasm (Prinzmetal’s angina), even in patients without a history of CAD. Perform a cardiovascular evaluation in triptan-naive patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving Sumavel DosePro. If there is evidence of CAD or coronary artery vasospasm, Sumavel DosePro is contraindicated. For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first dose of Sumavel DosePro in a medically supervised setting and performing an electrocardiogram (ECG) immediately following Sumavel DosePro. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of Sumavel DosePro. 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-HT1 agonists. Discontinue Sumavel DosePro if these disturbances occur. Sumavel DosePro is contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders. 5.3 Chest, Throat, Neck, and/or Jaw Pain/Tightness/Pressure Sensations of tightness, pain, pressure, and heaviness in the precordium, throat, neck, and jaw commonly occur after treatment with Sumavel DosePro and are usually non-cardiac in origin. However, perform a cardiac evaluation if these patients are at high cardiac risk. The use of Sumavel DosePro is contraindicated in patients shown to have CAD and those with Prinzmetal’s variant angina. 5.4 Cerebrovascular Events Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred 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 5-HT 1 agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine when they were not. Also, patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA). Discontinue Sumavel DosePro if a cerebrovascular event occurs. Before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with atypical symptoms, exclude other potentially serious neurological conditions. Sumavel DosePro is contraindicated in patients with a history of stroke or TIA. 5.5 Other Vasospasm Reactions Sumavel DosePro, 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 non-coronary vasospasm reaction following the use of any 5-HT 1 agonist, rule out a vasospastic reaction before receiving additional doses of Sumavel DosePro. 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 Sumavel DosePro, particularly during co-administration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors [see Drug Interactions ( 7.4 ) ] . 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 Sumavel DosePro 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 Sumavel DosePro. Sumavel DosePro is contraindicated in patients with uncontrolled hypertension. 5.9 Anaphylactic/Anaphylactoid Reactions There have been reports of anaphylaxis, anaphylactoid, and hypersensitivity reactions including angioedema in patients receiving Sumavel DosePro. 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. Sumavel DosePro is contraindicated in patients with a history of hypersensitivity reaction to Sumavel DosePro. 5.10 Seizures Seizures have been reported following administration of Sumavel DosePro. Some have occurred in patients with either a history of seizures or concurrent conditions predisposing to seizures. There are also reports in patients where no such predisposing factors are apparent. Sumavel DosePro should be used with caution in patients with a history of epilepsy or conditions associated with a lowered seizure threshold.