WARNINGS AND PRECAUTIONS
Cardiovascular Thrombotic Events and Myocardial Infarction:
Avoid the use of
SYMBRAVO in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV
thrombotic events. If SYMBRAVO is used in patients with a recent MI, monitor patients for signs of cardiac
ischemia. Perform a cardiovascular evaluation in triptan-naive patients with multiple cardiovascular risk factors
and if satisfactory, consider administering the first dose in a medically supervised setting.
GI Bleeding, Ulceration, & Perforation:
NSAIDs, including meloxicam, a
component of SYMBRAVO, 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. These serious
adverse events can occur at any time, with or without warning symptoms, in patients treated with meloxicam.
Arrhythmias:
Life-threatening arrhythmias, including ventricular tachycardia
and ventricular fibrillation leading to death, have been reported within a few hours following the administration
of
5-HT1 agonists. Discontinue SYMBRAVO if these arrhythmias occur.
Cerebrovascular Events:
Cerebral hemorrhage, subarachnoid hemorrhage, and
stroke have occurred in patients treated with 5‑HT1 agonists, some resulting in fatalities. Discontinue SYMBRAVO
if any of these events occur.
Before treating headaches in patients not previously diagnosed with migraine, and in patients with migraine who
present with atypical symptoms, care should be taken to exclude other potentially serious neurological
conditions.
Anaphylactic Reactions:
SYMBRAVO can cause anaphylactic reactions in
patients with and without known hypersensitivity to meloxicam and in patients with aspirin-sensitive asthma.
Hypersensitivity reactions, including angioedema and anaphylaxis, have also occurred in patients receiving
rizatriptan. Seek emergency help if an anaphylactic reaction occurs.
Chest/Throat/Neck/Jaw Pain/Tightness, Pressure, or Heaviness:
Sensations of
tightness, pain, pressure in the chest, and heaviness in the precordium, throat, neck, and jaw commonly occur
after treatment with SYMBRAVO and are usually non-cardiac in origin. Perform a cardiac evaluation if a cardiac
origin is suspected.
Other Vasospasm Reactions:
SYMBRAVO may cause non-coronary vasospastic
reactions, such as peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction, splenic
infarction, and Raynaud’s syndrome. Discontinue SYMBRAVO if any of these events occur.
Reports of transient and permanent blindness and significant partial vision loss have been reported with the
use of 5-HT1 agonists.
Hepatotoxicity:
Elevations of ALT or AST have been reported in patients
taking NSAIDs. Rare, sometimes fatal cases of severe hepatic injury, including fulminant hepatitis, liver
necrosis, and hepatic failure have been reported. Inform patients of the warning signs and symptoms of
hepatotoxicity. Discontinue immediately if clinical signs and symptoms consistent with liver disease develop and
perform a clinical evaluation.
Hypertension/Increase in Blood Pressure (BP):
NSAIDs, including meloxicam, a
component of SYMBRAVO, can lead to new onset of hypertension or worsening of pre-existing hypertension, either of
which may contribute to the increased incidence of CV events. Patients taking angiotensin converting enzyme (ACE)
inhibitors, thiazides or loop diuretics may have impaired response to these therapies when taking NSAIDs.
Significant elevation in BP, 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, a component of SYMBRAVO.
Monitor BP during the initiation of the treatment and throughout the course of therapy.
Heart Failure and Edema:
Avoid the use of SYMBRAVO in patients with severe
heart failure unless the benefits are expected to outweigh the risk of worsening heart failure. If SYMBRAVO is
used in patients with severe heart failure, monitor patients for signs of worsening heart failure.
Renal Toxicity and Hyperkalemia:
Renal Toxicity - Long-term
administration of NSAIDs has resulted in serious renal injury, including acute renal failure. SYMBRAVO is not
recommended in patients with moderate to severe renal insufficiency and is contraindicated in patients with
moderate to severe renal insufficiency who are at risk for renal failure due to volume depletion. The renal
effects may hasten the progression of renal dysfunction in patients with pre-existing renal disease.
Correct volume status in dehydrated or hypovolemic patients prior to initiating SYMBRAVO. Monitor renal
function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia during use.
Avoid the use in patients with advanced renal disease unless the benefits are expected to outweigh the risk of
worsening renal function. If SYMBRAVO is used in patients with advanced renal disease, monitor patients for
signs of worsening renal function.
Hyperkalemia - Increases in serum potassium concentration, including hyperkalemia, have been reported
with use of NSAIDs, even in some patients without renal impairment.
Serious Skin Reactions:
NSAIDs, including SYMBRAVO, can cause serious skin
adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis
(TEN), which can be fatal. NSAIDs can also cause fixed drug eruption (FDE). FDE may present as a more severe
variant known as generalized bullous fixed drug eruption (GBFDE), which can be life-threatening. These serious
events may occur without warning. Discontinue SYMBRAVO at the first appearance of skin rash or any other sign of
hypersensitivity.
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS):
DRESS has
been reported in patients taking NSAIDs, such as SYMBRAVO. Some of these events have been fatal or
life-threatening. If signs or symptoms of DRESS are present, discontinue SYMBRAVO and evaluate the patient
immediately.
Fetal Toxicity:
Limit use of NSAIDs, including SYMBRAVO, between about 20 to
30 weeks in pregnancy due to the risk of oligohydramnios/fetal renal dysfunction. Avoid use of NSAIDs in women at
about 30 weeks gestation and later in pregnancy due to the risks of oligohydramnios/fetal renal dysfunction and
premature closure of the fetal ductus arteriosus.
Hematologic Toxicity:
Anemia has occurred in NSAID-treated patients. Monitor
hemoglobin or hematocrit in patients with any signs or symptoms of anemia. NSAIDs, including SYMBRAVO, may
increase the risk of bleeding events. Monitor patients for signs of bleeding.
Exacerbation of Asthma Related to Aspirin Sensitivity:
In patients with
preexisting asthma (without known aspirin sensitivity), monitor patients for changes in the signs and symptoms of
asthma.
Medication Overuse Headache:
Overuse of acute migraine drugs may lead to
exacerbation of headache. Detoxification and treatment of withdrawal may be necessary
Serotonin Syndrome:
Serotonin syndrome may occur with triptans, including
SYMBRAVO, particularly during co-administration with selective serotonin reuptake inhibitors (SSRIs), serotonin
norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, and MAOIs. Discontinue SYMBRAVO if
serotonin syndrome is suspected.
Masking of Inflammation and Fever:
The pharmacological activity of SYMBRAVO
in reducing inflammation, and possibly fever, may diminish the 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 monitoring patients on long-term NSAID treatment with
a
CBC and a chemistry profile periodically.
