warnings and cautions
5 WARNINGS AND PRECAUTIONS Myocardial ischemia, myocardial infarction, and Prinzmetal's angina: Perform cardiac evaluation in patients with multiple cardiovascular risk factors (5.1) Arrhythmias: Discontinue dosing if occurs (5.2) Chest/throat/neck/jaw pain, tightness, pressure, or heaviness; Generally not associated with myocardial ischemia; Evaluate patients at high risk (5.3) Cerebral hemorrhage, subarachnoid hemorrhage, and stroke: Discontinue dosing if occurs (5.4) Gastrointestinal ischemic events, peripheral vasospastic reactions: Discontinue dosing if occurs (5.5) Hypersensitivity Reactions: angioedema and anaphylaxis have occurred (5.6) Medication overuse headache: Detoxification may be necessary (5.7) Serotonin syndrome: Discontinue dosing if occurs (5.8) 5.1 Myocardial Ischemia, Myocardial Infarction, and Prinzmetal's Angina RizaFilm should not be given to patients with ischemic or vasospastic coronary artery disease. There have been rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within a few hours following administration of rizatriptan benzoate. Some of these reactions occurred in patients without known coronary artery disease (CAD). 5-HT1 agonists, including RizaFilm 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) before receiving RizaFilm. If there is evidence of CAD or coronary artery vasospasm, RizaFilm is contraindicated. For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first RizaFilm dose in a medically supervised setting and performing an electrocardiogram (ECG) immediately following RizaFilm administration. For such patients, consider periodic cardiovascular evaluation in intermittent long-term users of RizaFilm. 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 RizaFilm if these disturbances occur. RizaFilm is contraindicated in patients with Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorder. 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 rizatriptan, the active moiety in RizaFilm, and are usually noncardiac in origin. However, perform a cardiac evaluation if these patients are at a high cardiac risk. The use of RizaFilm is contraindicated in patients with 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-HT1 agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT1 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, transient ischemic attack). Discontinue RizaFilm if a cerebrovascular event occurs. Before treating headaches in patients not previously diagnosed with migraine or in patients who present with atypical symptoms, exclude other potentially serious neurological conditions. RizaFilm is contraindicated in patients with a history of stroke or transient ischemic attack. 5.5 Other Vasospasm Reactions 5-HT 1 agonists, including RizaFilm, 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 the suspected vasospasm reaction before receiving additional RizaFilm doses. 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 has not been clearly established. 5.6 Hypersensitivity Reactions Hypersensitivity reactions, including angioedema and anaphylaxis, have occurred in patients receiving rizatriptan, the active moiety in RizaFilm. 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. RizaFilm is contraindicated in patients with a history of hypersensitivity reaction to rizatriptan. 5.7 Medication Overuse Headache Overuse of acute migraine drugs (e.g., ergotamine, triptans, opioids, or a combination of 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 the 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. 5.8 Serotonin Syndrome Serotonin syndrome may occur with triptans, including RizaFilm, particularly during coadministration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors [see Drug Interactions (7.5) ]. 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 can occur within minutes to hours of receiving a new or a greater dose of a serotonergic medication. RizaFilm treatment should be discontinued if serotonin syndrome is suspected [see Drug Interactions (7.4) and Patient Counseling Information (17) ]. 5.9 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 with and without a history of hypertension receiving 5-HT1 agonists, including rizatriptan benzoate. In healthy young adult male and female patients who received maximal doses of rizatriptan benzoate (10 mg every 2 hours for 3 doses), slight increases in blood pressure (approximately 2-3 mmHg) were observed. RizaFilm is contraindicated in patients with uncontrolled hypertension [see Contraindications (4) ].