FDA label 61be400f-687b-4db4-8d15-8a7c1f8318cf

Ischemic Heart Disease: Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of angina pectoris and, in some cases, myocardial infarction have occurred. When discontinuing chronically administered metoprolol succinate extended-release tablets, particularly in patients with ischemic heart 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 succinate extended-release tablets 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 succinate extended-release tablets therapy abruptly even in patients treated only for hypertension.

WARNINGS Ischemic Heart Disease: Following abrupt cessation of therapy with certain beta-blocking agents, exacerbations of angina pectoris and, in some cases, myocardial infarction have occurred. When discontinuing chronically administered metoprolol succinate extended-release tablets, particularly in patients with ischemic heart 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 succinate extended-release tablets 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 succinate extended-release tablets therapy abruptly even in patients treated only for hypertension. Bronchospastic Diseases: PATIENTS WITH BRONCHOSPASTIC DISEASES SHOULD, IN GENERAL, NOT RECEIVE BETA-BLOCKERS. Because of its relative beta 1 -selectivity, however, metoprolol succinate extended-release tablets may be used with caution in patients with bronchospastic disease who do not respond to, or cannot tolerate, other antihypertensive treatment. Since beta 1 -selectivity is not absolute, a beta 2 -stimulating agent should be administered concomitantly, and the lowest possible dose of metoprolol succinate extended-release tablets should be used (see DOSAGE AND ADMINISTRATION ). Pheochromocytoma: If metoprolol succinate extended-release tablets are 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. Major Surgery: The necessity or desirability of withdrawing beta-blocking therapy prior to major surgery is controversial; the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures. Metoprolol succinate extended-release tablets, like other beta-blockers, is a competitive inhibitor of beta-receptor agonists, and its effects can be reversed by administration of such agents, e.g., dobutamine or isoproterenol. However, such patients may be subject to protracted severe hypotension. Difficulty in restarting and maintaining the heart beat has also been reported with beta-blockers. Diabetes and Hypoglycemia: Metoprolol succinate extended-release tablets should be used with caution in diabetic patients if a beta-blocking agent is required. Beta-blockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly affected. Thyrotoxicosis: Beta-adrenergic blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-blockade, which might precipitate a thyroid storm. Peripheral Vascular Disease: Beta-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease. Caution should be exercised in such individuals. Calcium Channel Blockers: Because of significant inotropic and chronotropic effects in patients treated with beta-blockers and calcium channel blockers of the verapamil and diltiazem type, caution should be exercised in patients treated with these agents concomitantly.

ADVERSE REACTIONS Hypertension and Angina Most adverse effects have been mild and transient. The following adverse reactions have been reported for immediate release metoprolol tartrate. 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, somnolence, 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; syncope; chest pain; and hypotension have been reported in about 1 of 100 patients (see CONTRAINDICATIONS , WARNINGS , and PRECAUTIONS ). Respiratory: Wheezing (bronchospasm) and dyspnea have been reported in about 1 of 100 patients (see WARNINGS ). Gastrointestinal: Diarrhea has occurred in about 5 of 100 patients. Nausea, dry mouth, gastric pain, constipation, flatulence, digestive tract disorders and heartburn have been reported in about 1 of 100 patients. Hypersensitive Reactions: Pruritus or rash have occurred in about 5 of 100 patients. Worsening of psoriasis has also been reported. Miscellaneous: Peyronie's disease has been reported in fewer than 1 of 100,000 patients. Musculoskeletal pain, blurred vision, decreased libido, 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. The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with metoprolol. Potential Adverse Reactions In addition, there are a variety of adverse reactions not listed above which have been reported with other beta-adrenergic blocking agents and should be considered potential adverse reactions to metoprolol succinate. 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, thrombocytopenic purpura. Hypersensitive Reactions: Fever combined with aching and sore throat, laryngospasm, and respiratory distress. Heart Failure In the MERIT-HF study, serious adverse events and adverse events leading to discontinuation of study medication were systematically collected. In the MERIT-HF study comparing metoprolol succinate extended-release tablets in daily doses up to 200 mg (mean dose 159 mg once-daily) (n=1990) to placebo (n=2001), 10.3% of metoprolol succinate extended-release tablets patients discontinued for adverse events vs. 12.2% of placebo patients. The table below lists adverse events in the MERIT-HF study that occurred at an incidence of equal to or greater than 1% in the metoprolol succinate extended-release tablets group and greater than placebo by more than 0.5%, regardless of the assessment of causality. Adverse Events Occurring in the MERIT-HF Study at an Incidence ≥ 1% in the Metoprolol Succinate Extended-Release Tablets Group and Greater than Placebo by More Than 0.5% Metoprolol Succinate Extended-Release Tablets N=1990 % of patients Placebo N=2001 % of patients Dizziness/vertigo 1.8 1.0 Bradycardia 1.5 0.4 Accident and/or injury 1.4 0.8 Other adverse events with an incidence of >1% on metoprolol succinate extended-release tablets and as common on placebo (within 0.5%) included myocardial infarction, pneumonia, cerebrovascular disorder, chest pain, dyspnea/dyspnea aggravated, syncope, coronary artery disorder, ventricular tachycardia/arrhythmia aggravated, hypotension, diabetes mellitus/diabetes mellitus aggravated, abdominal pain, and fatigue. Postmarketing Experience The following adverse reactions have been reported with metoprolol succinate extended-release tablets in worldwide postmarketing use, regardless of causality: Cardiovascular: 2 nd and 3 rd degree heart block, cardiogenic shock in patients with acute myocardial infarction. Gastrointestinal: hepatitis, vomiting. Hematologic: thrombocytopenia. Musculoskeletal: arthralgia. Nervous System/Psychiatric: anxiety/nervousness, hallucinations, paresthesia. Reproductive, male: impotence. Skin: increased sweating, photosensitivity, urticaria. Special Sense Organs: taste disturbances.

<table width="100%"> <caption>Adverse Events Occurring in the MERIT-HF Study at an Incidence &#x2265; 1% in the Metoprolol Succinate Extended-Release Tablets Group and Greater than Placebo by More Than 0.5% </caption> <col width="40.000%" align="left"/> <col width="30.000%" align="left"/> <col width="30.000%" align="left"/> <tbody> <tr> <td align="left" valign="top" styleCode="Toprule Lrule Rrule"/> <td align="center" valign="top" styleCode="Toprule Botrule">Metoprolol Succinate Extended-Release Tablets N=1990 % of patients </td> <td align="center" valign="top" styleCode="Toprule Botrule Rrule">Placebo N=2001 % of patients </td> </tr> <tr> <td align="left" valign="top" styleCode="Lrule Rrule">Dizziness/vertigo </td> <td align="center" valign="top">1.8 </td> <td align="center" valign="top" styleCode="Rrule">1.0 </td> </tr> <tr> <td align="left" valign="top" styleCode="Lrule Rrule">Bradycardia </td> <td align="center" valign="top">1.5 </td> <td align="center" valign="top" styleCode="Rrule">0.4 </td> </tr> <tr> <td align="left" valign="top" styleCode="Botrule Lrule Rrule">Accident and/or injury </td> <td align="center" valign="top" styleCode="Botrule">1.4 </td> <td align="center" valign="top" styleCode="Botrule Rrule">0.8 </td> </tr> </tbody> </table>