SYMBRAVO (rizatriptan benzoate/meloxicam)

There are 17 contraindications. Absolute contraindication.

Contraindication List
Acute myocardial infarction
Angina
Aspirin exacerbated respiratory disease
Cerebral ischemia
Cerebrovascular accident
Coronary artery disease
Hemiplegic migraine
History of roux-en-Y gastric bypass
Ischemic bowel disease
Myocardial ischemia
Peripheral vascular disease
Post-operative from CABG surgery
Pregnancy
Prinzmetal angina
Renal transplant
Serotonin syndrome
Severe uncontrolled hypertension

There are 17 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Acute myocardial infarction
Alcohol use disorder
Cardiac arrhythmia
Chronic heart failure
Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Gastrointestinal hemorrhage
Gastrointestinal perforation
Gastrointestinal ulcer
History of kidney donation
Increased risk of bleeding
Increased risk of bleeding due to coagulation disorder
Kidney disease with likely reduction in glomerular filtration rate (GFr)
Nephrectomy
Systemic mastocytosis
Thrombotic disorder
Tobacco smoker

There are 5 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Anemia
Chronic kidney disease stage 5 (failure) GFr<15 ml/min
Disease of liver
Edema
Hypertension

There are 67 severe adverse reactions.

More Frequent	Less Frequent
Dyspnea Palpitations	Bradycardia Cardiac arrhythmia Chest pain Chest tightness Edema Paresthesia Skin rash Tachycardia

Rare/Very Rare

Abnormal hepatic function tests Acute eruptions of skin Acute myocardial infarction Agranulocytosis Allergic dermatitis Anaphylaxis Anemia Angina Angioedema Aphthous stomatitis Asthma Body fluid retention Bronchospastic pulmonary disease Bullous dermatitis Cerebrovascular accident Chest tightness Colitis DRESS syndrome Drug-induced hepatitis Dyspnea Erythema multiforme Exfoliative dermatitis Facial edema Gastric ulcer Gastrointestinal hemorrhage Gastrointestinal perforation Gastrointestinal ulcer Hearing loss Hepatic failure Hyperkalemia Hypersensitivity drug reaction Hypertension Hypotension Interstitial nephritis Intracerebral hemorrhage Jaundice Leukopenia Nephrotoxicity Pancreatitis Pharyngitis Purpura Renal failure Renal papillary necrosis Serotonin syndrome Stevens-johnson syndrome Subarachnoid intracranial hemorrhage Tachyarrhythmia Tachycardia Thrombocytopenic disorder Tongue swelling Toxic epidermal necrolysis Urinary retention Urticaria Vasculitis Ventricular arrhythmias Wheezing Worsening of chronic heart failure

There are 90 less severe adverse reactions.

More Frequent

Less Frequent

Acute abdominal pain Diarrhea Dizziness Drowsy Fatigue General weakness Vomiting

Acute cognitive impairment Arthralgia Constipation Depression Diarrhea Dizziness Dry eye Dyspepsia Dysphagia Euphoria Flatulence Flu-like symptoms Flushing Headache disorder Hyperhidrosis Hypertension Hypoesthesia Irritability Muscle rigidity Muscle spasm Myalgia Nausea Neck stiffness Ocular irritation Pain Pruritus of skin Sensation of cold Sensation of warmth Tremor Upper respiratory infection Urinary tract infection Xerostomia

Rare/Very Rare

Acute abdominal pain Acute cognitive impairment Agitation Alopecia Ataxia Black tarry stools Blurred vision Chills Cough Disturbance of attention Drowsy Drug-induced hot flash Dysgeusia Edema Eructation Erythema Esophagitis Facial edema Fatigue Fever Flushing Gait abnormality Gastroesophageal reflux disease Hallucinations Hematuria Hyperhidrosis Increased urinary frequency Malaise Medication overuse headache Memory impairment Mood changes Nervousness Paresthesia Periorbital edema Polydipsia Polyuria Proteinuria Pruritus of skin Skin photosensitivity Skin rash Symptoms of anxiety Syncope Tinnitus Tremor Urticaria Vertigo Visual changes Vomiting Weight gain Weight loss Xerostomia

Meloxicam/rizatriptan has not been studied in pregnant women. However, there are data pertaining to the use of the individual components during pregnancy. 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. 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 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.

Use of NSAIDs, including meloxicam/rizatriptan, at about 30 weeks gestation or later in pregnancy increases the risk of premature closure of the fetal ductus arteriosus. 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/m2 ).

Increased incidence of septal heart defects was observed in rabbits treated throughout embryogenesis with meloxicam at an oral dose equivalent to 59 times the MRHD of 20 mg of meloxicam on a mg/m2 basis. In pre- and post-natal reproduction studies, there was an increased incidence of dystocia, delayed parturition, and decreased offspring survival at 0.06 times the MRHD of 20 mg of meloxicam on a mg/m2 basis.

No teratogenic effects were observed in rats and rabbits treated with meloxicam during organogenesis at an oral dose equivalent to 2 and 20 times, respectively, the MRHD of 20 mg of meloxicam on a mg/m2 basis. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization. In animal studies, administration of prostaglandin synthesis inhibitors, such as meloxicam, resulted in increased pre- and post-implantation loss.

Prostaglandins also have been shown to have an important role in fetal kidney development. In published animal studies, prostaglandin synthesis inhibitors have been reported to impair kidney development when administered at clinically relevant doses. Available human data on the use of rizatriptan in pregnant women are not sufficient to draw conclusions about drug-associated risk for major birth defects and miscarriage.

In animal studies, developmental toxicity was observed following oral administration of rizatriptan during pregnancy (decreased fetal body weight in rats) or throughout pregnancy and lactation (increased mortality, decreased body weight, and neurobehavioral impairment in rat offspring) at doses greater than the MRHD of 10 mg rizatriptan on a mg/m2 basis. In women with migraine, there is an increased risk of adverse perinatal outcomes in the mother, including pre-eclampsia and gestational hypertension. Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy, because NSAIDs, including meloxicam/rizatriptan, can cause premature closure of the fetal ductus arteriosus.

If an NSAID is necessary at about 20 weeks gestation or later in pregnancy, limit the use to the lowest effective dose and shortest duration possible. If meloxicam/rizatriptan treatment extends beyond 48 hours, consider monitoring with ultrasound for oligohydramnios. If oligohydramnios occurs, discontinue meloxicam/rizatriptan and follow up according to clinical practice.

There are no studies on the effects of meloxicam/rizatriptan during labor or delivery. In animal studies, NSAIDs, including meloxicam, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth.

There are no human data available on whether meloxicam is present in human milk, or on the effects on breastfed infants, or on milk production. 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 on 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 from the underlying maternal condition.

Clinical studies of meloxicam/rizatriptan did not include subjects 65 years of age and older to determine whether they respond differently from younger subjects. Elderly patients, compared to younger patients, are at greater risk for NSAID-associated serious cardiovascular, GI, hepatic, and/or renal adverse reactions. If the anticipated benefit for the elderly patient outweighs these potential risks, treat for the fewest number of days per month, as needed, and monitor patients for adverse effect.

Geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of coronary artery disease) should have a cardiovascular evaluation prior to receiving meloxicam/rizatriptan.