Meloxicam-Rizatriptan

Meloxicam-Rizatriptan is a combination medication indicated for acute treatment of migraine with or without aura in adults.

• Meloxicam-Rizatriptan is available under the following different brand names: Symbravo.

Common side effects of Meloxicam-Rizatriptan include:

• dizziness
• feeling tired

Serious side effects of Meloxicam-Rizatriptan include:

• heartbeats that are too fast or too slow (arrhythmias)
• new or worse high blood pressure
• heart failure
• liver problems including liver failure
• kidney problems including kidney failure
• low red blood cells (anemia)
• life-threatening skin reactions
• asthma attacks in people who have asthma
• stomach pain 
• constipation
• diarrhea
• gas
• heartburn
• nausea
• vomiting 
• dizziness 
• heart attack symptoms include chest discomfort in the center of the chest that lasts for more than a few minutes or that goes away and comes back, chest discomfort that feels like uncomfortable pressure, squeezing, fullness or pain, pain or discomfort in the arms, back, neck, jaw or stomach, shortness of breath with or without chest discomfort o breaking out in a cold sweat, nausea or vomiting, feeling lightheaded
• stroke symptoms include numbness or weakness in the face, arm, or leg, especially on one side of your body, confusion, problems speaking or understanding, problems seeing in 1 or both of your eyes, problems walking, dizziness, loss of balance or coordination
• stomach and intestinal problems include sudden or severe stomach pain, severe stomach pain after meals, sudden unexplained weight loss, severe nausea or vomiting, severe constipation or diarrhea, bloody diarrhea
• peripheral vascular ischemia symptoms include cramping and pain in the legs or hips, feeling of heaviness or tightness in your leg muscles, burning or aching pain in the feet or toes while resting, numbness, tingling, or weakness in the legs, cold feeling or color changes in 1 or both legs or feet
• medication overuse headaches
• serotonin syndrome symptoms include mental changes such as seeing things that are not there (hallucinations); agitation or coma, high body temperature, tight muscles, fast heartbeat, trouble walking, changes in your blood pressure

Rare side effects of Meloxicam-Rizatriptan include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 20 mg/10 mg

Migraine headache

Adult dosage

• 1 tablet (meloxicam 20 mg/rizatriptan 10 mg) orally as needed; not to exceed 1 tablet daily
• Safety of treatment, on average of more than 7 headaches/30 days has not been established

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Meloxicam-Rizatriptan has severe interactions with the following drug:
  • sodium polystyrene sulfonate
• Meloxicam-Rizatriptan has serious interactions with at least 19 other drugs
• Meloxicam-Rizatriptan has moderate interactions with at least 234 other drugs
• Meloxicam-Rizatriptan has minor interactions with at least 102 other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Ischemic coronary artery disease or other significant underlying cardiovascular disease
• Coronary artery vasospasm
• In the setting of coronary artery bypass graft (CABG) surgery
  • History of stroke or transient ischemic attack
  • Hemiplegic or basilar migraine
• Peripheral vascular disease
• Ischemic bowel disease
• Uncontrolled hypertension
• Coadministration with propranolol
• Recent (within 24 hours) use of an ergotamine-containing medication, ergot-type medication (.eg, dihydroergotamine, methysergide), another 5-HT1 agonist (.eg, another triptan)
• Concurrent administration or recent discontinuation (ie, within the past 2 weeks) of a MAO-A inhibitor
• Known hypersensitivity to meloxicam, rizatriptan, NSAIDs, triptans, or any excipients
• History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs
• Moderate-to-severe renal insufficiency in patients at risk for renal failure due to volume depletion or on dialysis

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Meloxicam-Rizatriptan?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Meloxicam-Rizatriptan?”

Cautions

• Cardiovascular (CV) thrombotic events and myocardial infarction
• NSAIDS
  • NSAID use may increase risk of serious CV thrombotic events (eg, myocardial infarction, stroke)
  • Use of NSAIDs in first 10-14 days following CABG surgery increased incidence of MI and stroke; NSAID use contraindicated in setting of CABG
  • NSAID use post-MI showed increased risk of reinfarction, CV-related death, and all-cause mortality beginning from first week of treatment
  • Minimize risk by using lowest effective dose for shortest duration possible
• Physicians and patients should remain alert for development of such events, throughout entire treatment course, even in absence of previous CV symptoms
• Inform patients about symptoms of serious CV events and steps to take if they occur
• There is no consistent evidence that concurrent use of aspirin mitigates risk of serious CV thrombotic events associated with NSAIDs; however, concurrent use of aspirin and NSAIDs increases risk of serious GI events

Rizatriptan

•  5-HT1 agonists may cause coronary artery vasospasm (Prinzmetal angina), even in patients without history of coronary artery disease (CAD); contraindicated with coronary artery vasospasm
• Perform CV evaluation in triptan-naïve patients with multiple CV risk factors (eg, increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD)
• Avoid use in patients with recent MI
• Gastrointestinal (GI) bleeding, ulceration, and perforation
• NSAIDs can cause serious GI adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal
• Patients with a history of peptic ulcer disease and/or GI bleeding who used NSAIDs have above 10-fold increased risk for developing a GI bleed compared to patients without these risk factors
• Other factors include
• Longer duration of NSAID therapy
• Concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective SSRIs
• Smoking
• Use of alcohol
• Older age
• Poor general health status
• Arrhythmias
• Life-threatening cardiac rhythm disturbances, including ventricular tachycardia and ventricular fibrillation leading to death, were reported within a few hours following the administration of 5-HT1 agonists
• Discontinue if these disturbances occur
• Cerebrovascular events
  • Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT1 agonists, some resulting in fatalities
  • In some cases, it appears possible that cerebrovascular events were primary and a 5-HT1 agonist was administered with incorrect belief that symptoms were a consequence of migraine, when they were not
  • Patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, transient ischemic attack [TIA])
  • Discontinue if cerebrovascular event occurs
  • Before treating headaches in patients not previously diagnosed with migraine, and in patients with migraine who present with atypical symptoms, exclude other potentially serious neurological conditions
• Contraindicated with history of strokes or TIA
• Anaphylactic reactions
  • Can cause anaphylactic reactions
  • Meloxicam is associated with anaphylactic reactions in patients with and without known hypersensitivity to meloxicam and patients with aspirin-sensitive asthma
  • Hypersensitivity reactions (eg, angioedema, anaphylaxis) have also occurred in patients receiving rizatriptan
  • Seek emergency help if anaphylactic reaction occurs
• Chest, throat, neck and/or jaw pain/tightness/pressure
• Sensations of tightness, pain, pressure, and heaviness in precordium, throat, neck and jaw commonly occur after treatment and are usually noncardiac in origin
• Evaluate patient if cardiac origin suspected
• Other vasospasm reactions
  • 5-HT1 agonists may cause noncoronary vasospastic reactions (e.g., peripheral vascular ischemia, GI vascular ischemia and infarction [presenting with abdominal pain and bloody diarrhea], splenic infarction, and Raynaud syndrome)
  • Rule out suspected vasospasm before prescribing additional doses
• Hepatotoxicity
  • May elevate ALT/AST
  • Rare, sometimes fatal, cases of severe hepatic injury, including fulminant hepatitis, liver necrosis, and hepatic failure reported
  • Inform patients of warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, diarrhea, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms)
  • Discontinue immediately and perform evaluation if clinical signs and symptoms consistent with liver disease develop or systemic manifestations (e.g., eosinophilia, rash) occur
• Hypertension
  • Can lead to a new onset hypertension or worsening pre-existing hypertension, either of which may contribute to increased incidence of CV events
  • Monitor BP while initiating treatment and throughout therapy
• Heart failure and edema
  • The Coxib and traditional NSAID Trialists’ Collaboration meta-analysis of randomized controlled trials demonstrated an approximately 2-fold increase in hospitalizations for heart failure in COX-2 selective-treated patients and nonselective NSAID-treated patients compared with placebo-treated patients
  • Fluid retention and edema were observed in some patients treated with NSAIDs
  • Meloxicam may blunt CV effects of several therapeutic agents used to treat these medical conditions (eg, diuretics, ACE inhibitors, ARBs)
  • Avoid use in patients with severe heart failure unless benefits are expected to outweigh risk of worsening heart failure; if used, monitor patients for signs of worsening heart failure
• Renal toxicity and hyperkalemia
  • Long-term administration of NSAIDs has resulted in renal papillary necrosis, renal insufficiency, acute renal failure, and other renal injury
  • NSAIDs are not recommended with moderate to severe renal insufficiency and are contraindicated in patients with moderate to severe renal insufficiency at risk for renal failure due to volume depletion
  • Increased serum potassium concentration (eg, hyperkalemia) reported with NSAIDs, even in some patients without renal impairment
  • Correct volume status in dehydrated or hypovolemic patients before initiating
• Serious skin reactions
  • Contraindicated in patients with previous serious skin reactions to NSAIDs
  • NSAIDs, including this drug, can cause serious skin adverse reactions such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal
  • NSAIDs can cause fixed-drug eruption (FDE); or generalized bullous fixed drug eruption (GBFDE) which can be life-threatening; these serious events may occur without warning
  • Inform patients about signs and symptoms of serious skin reactions, and to discontinue therapy at first appearance of skin rash or any other sign of hypersensitivity
• Drug reactions with eosinophilia and systemic symptoms (DRESS)
  • DRESS reported in patients taking NSAIDs; some events were fatal or life-threatening
  • DRESS typically presents with fever, rash, lymphadenopathy, and/or facial swelling
  • Other clinical manifestations may include hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis; sometimes symptoms of DRESS may resemble an acute viral infection
  • Eosinophilia is often present; because this disorder is variable in its presentation, other organ systems not noted here may be involved
  • Early manifestations of hypersensitivity (eg, fever, lymphadenopathy) may be present even though rash is not evident; if such signs or symptoms are present, discontinue therapy and evaluate patient immediately
• Older adults
  • Older adults are at greater risk for NSAID-associated serious cardiovascular, GI, hepatic, or renal adverse reactions
  • If anticipated benefit outweighs these potential risks, treat for fewest number of days per month, as needed, and monitor patients for adverse effects
  • Perform cardiovascular evaluation in older adults who have other cardiovascular risk factors (eg, diabetes, hypertension, smoking, obesity, strong family history of coronary artery disease)
• Fetal toxicity
  • Premature closure of fetal ductus arteriosus
  • Avoid use of NSAIDs in pregnant women at 30 weeks gestation and later
  • NSAIDs increased the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age
  • Oligohydramnios/neonatal renal impairment
  • Use of NSAIDs at about 20 weeks gestation or later in pregnancy may also cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment
  • These adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after NSAID initiation
  • Oligohydramnios is often reversible with treatment discontinuation; complications of prolonged oligohydramnios may include limb contractures and delayed lung maturation
• Hematologic toxicity
  • Anemia reported in NSAID-treated patients; may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis
  • If signs or symptoms of anemia occur, monitor hemoglobin or hematocrit
  • NSAIDs may increase risk of bleeding; monitor for signs of bleeding
  • Comorbid conditions, such as coagulation disorders, concomitant use of warfarin, other anticoagulants, antiplatelet agents (e.g., aspirin), SSRIs and SNRIs may increase this risk
• Exacerbation of asthma-related to aspirin sensitivity
  • Some patients with asthma may have aspirin-sensitive asthma, which may include
  • Chronic rhinosinusitis complicated by nasal polyps
  • Severe, potentially fatal bronchospasm
  • Intolerance to aspirin and other NSAIDs
  • Contraindicated in aspirin-sensitive asthma owing to cross-reactivity
  • Caution in patients with asthma without known aspirin sensitivity
• Medication overuse headache
  • Overuse of acute migraine drugs (e.g., ergotamine, triptans, opioids, or a combination of drugs for greater than 10 days per month) may lead to exacerbation of headache (medication overuse headache)
  • Medication overuse headaches may present as migraine-like daily headaches, or as a marked increase in the frequency of migraine attacks
  • Detoxification of patients, including withdrawal of overused drugs, and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary
• Serotonin syndrome
  • Serotonin syndrome may occur with triptans, particularly when coadministered with SSRIs, SNRIs, TCAs, and MAO inhibitors
  • Symptoms onset can occur within minutes to hours of receiving a new or higher dose of serotonergic medication
  • Discontinue if serotonin syndrome suspected
  • Serotonin syndrome symptoms may include
    • Mental status changes (eg, agitation, hallucinations, coma)
    • Autonomic instability (eg, tachycardia, labile blood pressure, hyperthermia)
    • Neuromuscular aberrations (eg, hyperreflexia, incoordination)
    • GI symptoms (eg, nausea, vomiting, diarrhea)
    • Masking of inflammation and fever
    • NSAIDs reduce inflammation, and possibly fever, which may diminish utility of diagnostic signs in detecting infections
• Laboratory monitoring
  • Because serious GI bleeding, hepatotoxicity, and renal injury can occur without warning symptoms or signs, consider periodic monitoring patients on long-term NSAID treatment with complete blood counts (CBC) and chemistry profiles
  • Discontinue if GI bleeding occurs or if abnormal liver or renal tests persist or worsen

Pregnancy and Lactation

Meloxicam

• Use of NSAIDs, including Meloxicam-Rizatriptan, 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 the dose and duration of Meloxicam-Rizatriptan use between about 20 and 30 weeks of gestation, and avoid Meloxicam-Rizatriptan use at about 30 weeks of gestation and later in pregnancy

Rizatriptan

• Available human data on the use of rizatriptan in pregnant women are not sufficient to conclude drug-associated risk for major birth defects and miscarriage

Lactation

• Meloxicam
  • There are no human data available on whether meloxicam is present in human milk, on the effects on breastfed infants, or milk production.
• Rizatriptan
  • There are no adequate data on the presence of rizatriptan or any active metabolites in human milk, or on the effects of rizatriptan on the breastfed infant, or milk production. Rizatriptan was excreted in rat milk with levels in milk approximately 6 times those in maternal plasma.
  • The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Meloxicam-Rizatriptan and any potential adverse effects on the breastfed infant from the Meloxicam-Rizatriptan or the underlying maternal condition.