FDA label d7f5af35-4b80-484e-a0eb-98fb14d1fd3a

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 DUTOPROL, particularly in patients with ischemic heart disease, gradually reduce the dosage over a period of 1–2 weeks and monitor the patient. If angina markedly worsens or acute coronary ischemia develops, promptly reinstate DUTOPROL, and take measures appropriate for the management of unstable angina. Warn patients not to interrupt therapy without the physician’s advice. Because coronary artery disease is common and may be unrecognized, avoid abruptly discontinuing DUTOPROL in patients treated only for hypertension.

WARNINGS Metoprolol succinate extended release 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 DUTOPROL, particularly in patients with ischemic heart disease, gradually reduce the dosage over a period of 1–2 weeks and monitor the patient. If angina markedly worsens or acute coronary ischemia develops, promptly reinstate DUTOPROL, and take measures appropriate for the management of unstable angina. Warn patients not to interrupt therapy without the physician’s advice. Because coronary artery disease is common and may be unrecognized, avoid abruptly discontinuing DUTOPROL in patients treated only for hypertension. Bronchospastic Disease: PATIENTS WITH BRONCHOSPASTIC DISEASES SHOULD, IN GENERAL, NOT RECEIVE BETA-BLOCKERS. Because of its relative beta 1 cardio-selectivity, however, metoprolol succinate extended release/hydrochlorothiazide 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 DUTOPROL. Bronchodilators, including beta 2 —agonists, should be readily available or administered concomitantly (see DOSAGE AND ADMINISTRATION ). Pheochromocytoma: If DUTOPROL 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. Major Surgery: Avoid initiation of high-dose regimen of extended— release metoprolol in patients undergoing non-cardiac surgery, since such use in patients with cardiovascular risk factors has been associated with bradycardia, hypotension, stroke and death. 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. Diabetes and Hypoglycemia: Beta-blockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be significantly affected. (See PRECAUTIONS, General, Hydrochlorothiazide ). Thyrotoxicosis: Beta-adrenergic blockade may mask certain clinical signs of hyperthyroidism, such as tachycardia. 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. 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 Metoprolol succinate extended release/hydrochlorothiazide The metoprolol succinate extended release and hydrochlorothiazide combination was evaluated for safety in 891 patients treated for hypertension in clinical trials. In a placebo-controlled trial, 843 patients were treated with various combinations of metoprolol succinate (doses of 25 to 200 mg) and hydrochlorothiazide (doses of 6.25 to 25 mg). Overall, the incidence of adverse experiences reported with the combination was comparable to placebo. Adverse events, whether or not attributed to treatment, occurring in greater than 1% of patients treated with DUTOPROL and at a rate equal to or greater than with placebo were: nasopharyngitis (3.4% vs 1.3%), fatigue (2.6% vs 0.7%), dizziness (2.6% vs 2.6%), back pain (1.7% vs 1.3%), and nausea (1.4% vs 0.7%). Adverse experiences were usually mild and transient in nature and infrequently required discontinuation of therapy (2.7% vs 2.6% with placebo). Metoprolol 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 _Refwilliamsonbk1170269683944 , 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 DUTOPROL. 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. Post-Marketing Experience In addition, the following adverse reactions have been reported with metoprolol succinate in worldwide post-marketing use, regardless of causality: Cardiovascular: 2 nd and 3 rd degree heart block. 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. Hydrochlorothiazide Other adverse experiences that have been reported with hydrochlorothiazide, without regard to causality, are listed below: Body As A Whole: weakness; Cardiovascular: hypotension including orthostatic hypotension (may be aggravated by alcohol, barbiturates, narcotics or antihypertensive drugs); Digestive: pancreatitis, jaundice (intrahepatic cholestatic jaundice), diarrhea, vomiting, sialadenitis, cramping, constipation, gastric irritation, nausea, anorexia; Hematologic: aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia; Hypersensitivity: anaphylactic reactions, necrotizing angiitis (vasculitis and cutaneous vasculitis), respiratory distress including pneumonitis and pulmonary edema, photosensitivity, fever, urticaria, rash, purpura; Metabolic: electrolyte imbalance, glycosuria; Musculoskeletal: muscle spasm; Nervous System/Psychiatric: Vertigo, paresthesias, dizziness, headache, restlessness; Renal: renal failure, renal dysfunction, interstitial nephritis; Skin: erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis, alopecia; Special Senses: transient blurred vision, xanthopsia; Urogenital: impotence. LABORATORY TEST FINDINGS In controlled clinical trials, clinically important changes in standard laboratory parameters were infrequently associated with the administration of DUTOPROL. The laboratory test findings with metoprolol or hydrochlorothiazide or their combination may include: Creatinine, Blood Urea Nitrogen —Minor increases in blood urea nitrogen (BUN) . (See WARNINGS, Renal Disease .) Serum Electrolytes —Declines in serum potassium, sodium, chloride, magnesium. Increases in serum calcium and uric acid. (See PRECAUTIONS ). Glucose —Increase in serum or blood glucose. (See PRECAUTIONS, General, Hydrochlorothiazide .) Lipids —Increase in serum total cholesterol, triglycerides. Decreases in high density lipoprotein (HDL). Liver Function Tests —Increases in liver enzymes and/or serum bilirubin.