Metoprolol Tartrate 50 mg Tablet, Film Coated, 360-count — NDC 71610-565-94 (Billing 71610-0565-94)

WARNINGS Heart Failure Beta-blockers, like metoprolol, can cause depression of myocardial contractility and may precipitate heart failure and cardiogenic shock. If signs or symptoms of heart failure develop, treat the patient according to recommended guidelines. It may be necessary to lower the dose of metoprolol or to discontinue it.

Ischemic Heart Disease Do not abruptly discontinue metoprolol therapy in patients with coronary artery disease. Severe exacerbation of angina, myocardial infarction and ventricular arrhythmias have been reported in patients with coronary artery disease following the abrupt discontinuation of therapy with beta-blockers. When discontinuing chronically administered metoprolol, particularly in patients with coronary artery disease, the dosage should be gradually reduced over a period of 1 to 2 weeks and the patient should be carefully monitored.

If angina markedly worsens or acute coronary insufficiency develops, metoprolol administration should be reinstated promptly, at least temporarily, and other measures appropriate for the management of unstable angina should be taken. Patients should be warned against interruption or discontinuation of therapy without the physician’s advice. Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue metoprolol therapy abruptly even in patients treated only for hypertension.

Use During Major Surgery Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures. Bradycardia Bradycardia, including sinus pause, heart block, and cardiac arrest have occurred with the use of metoprolol. Patients with first-degree atrioventricular block sinus node dysfunction or conduction disorders may be at increased risk.

Monitor heart rate and rhythm in patients receiving metoprolol. If severe bradycardia develops, reduce or stop metoprolol. Exacerbation of Bronchospastic Disease Patients with bronchospastic disease, should, in general, not receive beta-blockers, including metoprolol.

Because of its relative beta 1 selectivity, however, metoprolol may be used in patients with bronchospastic disease who do not respond to, or cannot tolerate, other antihypertensive treatment. Because beta 1 selectivity is not absolute use the lowest possible dose of metoprolol and consider administering metoprolol in smaller doses 3 times daily, instead of larger doses 2 times daily, to avoid the higher plasma levels associated with the longer dosing interval (see DOSAGE AND ADMINISTRATION ). Bronchodilators, including beta 2 agonists, should be readily available or administered concomitantly.

Diabetes and Hypoglycemia Beta-blockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly affected. Pheochromocytoma If metoprolol is used in the setting of pheochromocytoma, it should be given in combination with an alpha-blocker, and only after the alpha-blocker has been initiated. Administration of beta-blockers alone in the setting of pheochromocytoma has been associated with a paradoxical increase in blood pressure due to the attenuation of beta-mediated vasodilatation in skeletal muscle.

Thyrotoxicosis Metoprolol may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Avoid abrupt withdrawal of beta-blockade, which might precipitate a thyroid storm.

ADVERSE REACTIONS Hypertension and Angina Most adverse effects have been mild and transient. Central Nervous System Tiredness and dizziness have occurred in about 10 of 100 patients. Depression has been reported in about 5 of 100 patients.

Mental confusion and short-term memory loss have been reported. Headache, nightmares, and insomnia have also been reported. Cardiovascular Shortness of breath and bradycardia have occurred in approximately 3 of 100 patients.

Cold extremities; arterial insufficiency, usually of the Raynaud type; palpitations; congestive heart failure; peripheral edema; and hypotension have been reported in about 1 of 100 patients. Gangrene in patients with preexisting severe peripheral circulatory disorders has also been reported very rarely (see CONTRAINDICATIONS , WARNINGS , and PRECAUTIONS ). Respiratory Wheezing (bronchospasm) and dyspnea have been reported in about 1 of 100 patients (see WARNINGS ).

Rhinitis has also been reported. Gastrointestinal Diarrhea has occurred in about 5 of 100 patients. Nausea, dry mouth, gastric pain, constipation, flatulence, and heartburn have been reported in about 1 of 100 patients.

Vomiting was a common occurrence. Post-marketing experience reveals very rare reports of hepatitis, jaundice and nonspecific hepatic dysfunction. Isolated cases of transaminase, alkaline phosphatase, and lactic dehydrogenase elevations have also been reported.

Hypersensitive Reactions Pruritus or rash have occurred in about 5 of 100 patients. Very rarely, photosensitivity and worsening of psoriasis have been reported. Miscellaneous Peyronie’s disease has been reported in fewer than 1 of 100,000 patients.

Musculoskeletal pain, blurred vision, and tinnitus have also been reported. There have been rare reports of reversible alopecia, agranulocytosis, and dry eyes. Discontinuation of the drug should be considered if any such reaction is not otherwise explicable.

There have been very rare reports of weight gain, arthritis, and retroperitoneal fibrosis (relationship to metoprolol has not been definitely established). The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with metoprolol. Myocardial Infarction Central Nervous System Tiredness has been reported in about 1 of 100 patients.

Vertigo, sleep disturbances, hallucinations, headache, dizziness, visual disturbances, confusion, and reduced libido have also been reported, but a drug relationship is not clear. Cardiovascular In the randomized comparison of metoprolol and placebo described in the CLINICAL PHARMACOLOGY section, the following adverse reactions were reported: Metoprolol Tartrate Tablets Placebo Hypotension (systolic BP < 90 mmHg) 27.4% 23.2% Bradycardia (heart rate < 40 beats/min) 15.9% 6.7% Second- or third-degree heart block 4.7% 4.7% First-degree heart block (P-R ≥ 0.26 sec) 5.3% 1.9% Heart failure 27.5% 29.6% Respiratory Dyspnea of pulmonary origin has been reported in fewer than 1 of 100 patients.

Gastrointestinal Nausea and abdominal pain have been reported in fewer than 1 of 100 patients. Dermatologic Rash and worsened psoriasis have been reported, but a drug relationship is not clear. Miscellaneous Unstable diabetes and claudication have been reported, but a drug relationship is not clear.

Potential Adverse Reactions A variety of adverse reactions not listed above have been reported with other beta-adrenergic blocking agents and should be considered potential adverse reactions to metoprolol. Central Nervous System Reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emotional lability, slightly clouded sensorium, and decreased performance on neuropsychometrics. Cardiovascular Intensification of AV block (see CONTRAINDICATIONS ).

Hematologic Agranulocytosis, nonthrombocytopenic purpura and thrombocytopenic purpura. Hypersensitive Reactions Fever combined with aching and sore throa…

Drug Interactions Catecholamine-Depleting Drugs Catecholamine-depleting drugs (e.g., reserpine) may have an additive effect when given with beta-blocking agents or monoamine oxidase (MAO) inhibitors. Observe patients treated with metoprolol plus a catecholamine depletor for evidence of hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension. In addition, possibly significant hypertension may theoretically occur up to 14 days following discontinuation of the concomitant administration with an irreversible MAO inhibitor.

Digitalis Glycosides and Beta-Blockers Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia. Monitor heart rate and PR interval.

Calcium Channel Blockers Concomitant administration of a beta-adrenergic antagonist with a calcium channel blocker may produce an additive reduction in myocardial contractility because of negative chronotropic and inotropic effects.