Meloxicam and Rizatriptan

SYMBRAVO is indicated for the acute treatment of migraine with or without aura in adults. Limitations of Use SYMBRAVO should only be used where a clear diagnosis of migraine has been established. If a patient has no response for the first migraine attack treated with SYMBRAVO, the diagnosis of migraine should be reconsidered before SYMBRAVO is administered to treat any subsequent attacks. SYMBRAVO is not indicated for the preventive treatment of migraine attacks. SYMBRAVO is not indicated for the treatment of cluster headache. SYMBRAVO is a combination of meloxicam (an NSAID) and rizatriptan (a serotonin (5-HT) 1B/1D receptor agonist (triptan)), indicated for the acute treatment of migraine with or without aura in adults. SYMBRAVO is not indicated for the preventive treatment of migraine.

SYMBRAVO contains meloxicam and rizatriptan. Meloxicam has analgesic, anti-inflammatory, and antipyretic properties. The mechanism of action of meloxicam, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2). Meloxicam is a potent inhibitor of prostaglandin synthesis in vitro. Meloxicam concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models. Prostaglandins are mediators of inflammation. Because meloxicam is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues. Rizatriptan binds with high affinity to human cloned 5-HT 1B/1D receptors.

The recommended dose of SYMBRAVO is one tablet by mouth as needed. The maximum daily dose is 20 mg meloxicam and 10 mg rizatriptan (1 tablet).

SYMBRAVO is contraindicated in patients with: Ischemic coronary artery disease (angina pectoris, history of myocardial infarction, or documented silent ischemia), or other significant underlying cardiovascular disease. Coronary artery vasospasm including Prinzmetal’s angina. In the setting of coronary artery bypass graft (CABG) surgery. History of stroke or transient ischemic attack (TIA). Hemiplegic or basilar migraine. Peripheral vascular disease (PVD). Ischemic bowel disease. Uncontrolled hypertension.

Boxed warning (risk of serious cardiovascular and gastrointestinal events): Cardiovascular Risk Non-steroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use. SYMBRAVO is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Cardiovascular Thrombotic Events, Myocardial Ischemia, Myocardial Infarction, and Prinzmetal's Angina: Perform cardiac evaluation in patients with multiple cardiovascular risk factors. Arrhythmias: Discontinue dosing if arrhythmia occurs. Cerebral Hemorrhage, Subarachnoid Hemorrhage, and Stroke: Discontinue dosing if occurs. Anaphylactic Reactions: Seek emergency help if an anaphylactic reaction occurs.

The following adverse reactions are discussed in more detail in other sections of the labeling: Cardiovascular Thrombotic Events and Myocardial Infarction GI Bleeding, Ulceration, and Perforation Arrhythmias Cerebrovascular Events Anaphylactic Reactions Chest, Throat, Neck and/or Jaw Pain/Tightness/Pressure Other Vasospasm Reactions Hepatotoxicity Hypertension/Increase in Blood Pressure Heart Failure and Edema Renal Toxicity and Hyperkalemia Serious Skin Reactions Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Fetal Toxicity Hematologic Toxicity Exacerbation of Asthma Related to Aspirin Sensitivity Medication Overuse Headache Serotonin Syndrome Most common adverse reactions (≥1% and greater than placebo) are dizziness and somnolence.

Drugs that Interfere with Hemostasis (e.g., warfarin, aspirin, SSRIs/SNRIs): Monitor patients for bleeding who are concomitantly taking SYMBRAVO with drugs that interfere with hemostasis. Concomitant use of SYMBRAVO and analgesic doses of aspirin is not generally recommended. ACE Inhibitors, ARBs, or Beta-Blockers: Concomitant use with SYMBRAVO may diminish the antihypertensive effect of these drugs. Monitor blood pressure. ACE Inhibitors and ARBs: Concomitant use with SYMBRAVO in elderly, volume-depleted, or those with renal impairment may result in deterioration of renal function. In such high-risk patients, monitor for signs of worsening renal function. Diuretics: NSAIDs can reduce natriuretic effect of furosemide and thiazide diuretics. Monitor patients to assure diuretic efficacy including antihypertensive effects. Lithium: Monitor for increases in lithium plasma levels.

Store SYMBRAVO in the original bottle at 20°C to 25°C (68°F to 77°F), excursions permitted to 15°C to 30°C (59°F to 86°F).