⛔ FDA Black Box Warning
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 [see Warnings & Precautions (5.1) ] . SYMBRAVO is contraindicated in the setting of coronary artery bypass graft (CABG) surgery [see Contraindications (4) , Warnings & Precautions (5.1) ] . Gastrointestinal Risk NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events [see Warnings & Precautions (5.2) ] . WARNING: RISK OF SERIOUS CARDIOVASCULAR AND GASTROINTESTINAL EVENTS See full prescribing information for complete boxed warning. 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 (5.1) . SYMBRAVO is contraindicated in the setting of coronary artery bypass graft (CABG) surgery ( 4 , 5.1 ). NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events ( 5.2 ).
Contraindications
4 CONTRAINDICATIONS 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 [see Warnings & Precautions (5.1) ] . Coronary artery vasospasm including Prinzmetal’s angina [see Warnings & Precautions (5.1) ] . In the setting of coronary artery bypass graft (CABG) surgery [see Warnings & Precautions (5.1) ] . History of stroke or transient ischemic attack (TIA) [see Warnings & Precautions (5.4) ] . Hemiplegic or basilar migraine. Peripheral vascular disease (PVD) [see Warnings & Precautions (5.7) ] . Ischemic bowel disease [see Warnings & Precautions (5.7) ] . Uncontrolled hypertension [see Warnings & Precautions (5.9) ] . Concomitant use of propranolol [see Drug Interactions (7.1) ] Recent use (i.e., within 24 hours) of an ergotamine-containing medication, ergot-type medication (such as dihydroergotamine or methysergide), or another 5-HT1 agonist (e.g., another triptan) [see Drug Interactions (7.1) ] . Concurrent administration or recent discontinuation (i.e., within 2 weeks) of a MAO-A inhibitor [see Drug Interactions (7.1) , Clinical Pharmacology (12.3) ] . Known hypersensitivity (e.g., anaphylactic reactions and angioedema seen) to SYMBRAVO, meloxicam, rizatriptan, NSAIDs or any of the excipients in SYMBRAVO [see Warnings & Precautions (5.5) , Adverse Reactions (6.2) ] . History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal anaphylactic-like reactions to NSAIDs have been reported in such patients [see Warnings & Precautions (5.16 )] . Moderate to severe renal insufficiency in patients who are at risk for renal failure due to volume depletion or who are on dialysis [see Warnings & Precautions (5.11 )]. Ischemic coronary artery disease or other significant underlying cardiovascular disease ( 4 ) Coronary artery vasospasm ( 4 ) In the sett
Pregnancy & Breastfeeding
8.1 Pregnancy SYMBRAVO has not been studied in pregnant women. However, there are data pertaining to the use of the individual components, meloxicam and rizatriptan during pregnancy. These data are described below. Risk Summary In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The reported rate of major birth defects among infants born to women with migraine range from 2.2% to 2.9% and the reported rate of miscarriage was 17%, which are similar to rates reported in women without migraine. Meloxicam Use of NSAIDs, including SYMBRAVO, can cause premature closure of the fetal ductus arteriosus and fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. Because of these risks, limit dose and duration of SYMBRAVO use between about 20 and 30 weeks of gestation, and avoid SYMBRAVO use at about 30 weeks of gestation and later in pregnancy [see Clinical Considerations, Data] . Premature Closure of Fetal Ductus Arteriosus Use of NSAIDs, including SYMBRAVO, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. Oligohydramnios/Neonatal Renal Impairment Use of NSAIDs at about 20 weeks gestation or later in pregnancy has been associated with cases of fetal renal dysfunction leading to oligohydramnios, and in some cases, neonatal renal impairment. Data from observational studies regarding other potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In animal reproduction studies, embryofetal death was observed in rats and rabbits treated during the period of organogenesis with meloxicam at oral doses equivalent to 0.5 and 4.9 times, respectively, the maximum recommended human dose (MRHD) of 20 mg of meloxicam, based on body surface area (mg/m 2 ). Increased incidence of septal heart def