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 ) Medication overuse headache: Detoxification may be necessary ( 5.6 ) Serotonin syndrome: Discontinue dosing if occurs ( 5.7 ) 5.1 Myocardial Ischemia, Myocardial Infarction, and Prinzmetals Angina Keep rizatriptan benzoate orally disintegrating tablets and all medicines out of the reach of children. General Information about the safe and effective use of rizatriptan benzoate orally disintegrating tablets. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use rizatriptan benzoate for a condition for which it was not prescribed. Do not give rizatriptan benzoate orally disintegrating tablets to other people, even if they have the same symptoms that you have. It may harm them. This Patient Information leaflet summarizes the most important information about rizatriptan benzoate orally disintegrating tablets. If you would like more information, talk to your doctor. You can ask your pharmacist or doctor for information about rizatriptan benzoate orally disintegrating tablets that is written for health professionals. For more information, call Unichem Pharmaceuticals (USA), Inc. at 1-866-562-4616 What are the ingredients in rizatriptan benzoate orally disintegrating tablets? Active ingredient in rizatriptan benzoate orally disintegrating tablets: rizatriptan benzoate. Inactive ingredients in rizatriptan benzoate orally disintegrating tablets: colloidal silicon dioxide, crospovidone, magnesium stearate, mannitol, microcrystalline cellulose, orange flavor, sucralose. * The brand names mentioned are registered trademarks of their respective manufacturers. This Patient Information has been approved by the U.S. Food and Drug Administration. Additional patient information leaflets can be obtained by calling Unichem at 1-866-562-4616. Manufactured by: UNICHEM LABORATORIES LTD. Pilerne Ind. Estate, Pilerne, Bardez, Goa – 403 511, India Manufactured for: 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 rizatriptan benzoate if these disturbances occur. 5.3 Chest, Throat, Neck and/or Jaw Pain/Tightness/Pressure As with other 5-HT 1 agonists, sensations of tightness, pain, pressure, and heaviness in the precordium, throat, neck and jaw commonly occur after treatment with rizatriptan benzoate and are usually non-cardiac in origin. However, if a cardiac origin is suspected, patients should be evaluated. Patients shown to have CAD and those with Prinzmetal's variant angina should not receive 5-HT 1 agonists. 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, transient ischemic attack). Discontinue rizatriptan benzoate if a cerebrovascular event occurs. As with other acute migraine therapies, before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with atypical symptoms, care should be taken to exclude other potentially serious neurological conditions. Rizatriptan benzoate should not be administered to patients with a history of stroke or transient ischemic attack [see Contraindications ( 4 )] . 5.5 Other Vasospasm Reactions 5-HT 1 agonists, including rizatriptan benzoate, 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, the suspected vasospasm reaction should be ruled out before receiving additional rizatriptan benzoate doses. 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 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 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 triptans, including rizatriptan benzoate particularly during co-administration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors [see Drug Interactions ( 7.5 )] . 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. Rizatriptan benzoate treatment should be discontinued if serotonin syndrome is suspected [see Drug Interactions ( 7.4 ) and Patient Counseling Information ( 17 )] . 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 with and without a history of hypertension receiving 5-HT 1 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. Rizatriptan benzoate is contraindicated in patients with uncontrolled hypertension [see Contraindications ( 4 )] .