Metoprolol Tartrate Tablets,USP

DESCRIPTION

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displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Metoprolol tartrate, USP is a selective beta₁-adrenoreceptor blocking agent, available as 25, 50 and 100 mg tablets for oral administration. Metoprolol tartrate is (±)-1-(isopropylamino)-3-[p-(2-methoxyethyl)phenoxy]-2-propanol (2:1) dextro-tartrate salt, and its structural formula is Metoprolol tartrate, USP is a white, practically odorless, crystalline powder with a molecular weight of 684.81. It is very soluble in water; freely soluble in methylene chloride, in chloroform, and in alcohol; slightly soluble in acetone; and insoluble in ether. Each tablet for oral administration contains 25 mg, 50 mg or 100 mg of metoprolol tartrate USP and the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hypromellose, lactose anhydrous, magnesium stearate, microcrystalline cellulose, sodium starch glycolate, polyethylene glycol, pregelatinized starch, titanium dioxide. In addition the 25 mg and 100 mg tablet contain propylene glycol and sodium lauryl sulfate; the 50 mg tablet contains D&C Red #30 and talc.

INDICATIONS AND USAGE

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displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

Hypertension Metoprolol tartrate tablets are indicated for the treatment of hypertension. They may be used alone or in combination with other antihypertensive agents. Angina Pectoris Metoprolol tartrate is indicated in the long-term treatment of angina pectoris. Myocardial Infarction Metoprolol tartrate tablets are indicated in the treatment of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality when used alone or in conjunction with intravenous metoprolol tartrate. Oral metoprolol tartrate therapy can be initiated after intravenous metoprolol tartrate therapy or, alternatively, oral treatment can begin within 3 to 10 days of the acute event (see DOSAGE AND ADMINISTRATION, CONTRAINDICATIONS, and WARNINGS).

CONTRAINDICATIONS

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displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

Hypertension and Angina Metoprolol tartrate is contraindicated in sinus bradycardia, heart block greater than first degree, cardiogenic shock, and overt cardiac failure (see WARNINGS). Hypersensitivity to metoprolol tartrate and related derivatives, or to any of the excipients; hypersensitivity to other beta blockers (cross sensitivity between beta blockers can occur). Sick-sinus syndrome. Severe peripheral arterial circulatory disorders. Myocardial Infarction Metoprolol tartrate is contraindicated in patients with a heart rate <45 beats/min; second-and third-degree heart block; significant first-degree heart block (P-R interval ≥0.24 sec); systolic blood pressure <100 mmHg; or moderate-to-severe cardiac failure (see WARNINGS).

ADVERSE REACTIONS

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displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

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 pre-existing 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. Postmarketing experience reveals very rare reports of hepatitis, jaundice and non-specific 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 has 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 tartrate has not been definitely established). The oculomucocutaneous syndrome associated with the beta blocker practolol has not been reported with metoprolol tartrate. 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 tartrate and placebo described in the CLINICAL PHARMACOLOGY section, the following adverse reactions were reported:

	Metoprolol  Tartrate	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 tartrate.
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 throat, laryngospasm and respiratory distress. Postmarketing Experience The following adverse reactions have been reported during postapproval use of metoprolol tartrate: confusional state, an increase in blood triglycerides and a decrease in High Density Lipoprotein (HDL). Because these reports are from a population of uncertain size and are subject to confounding factors, it is not possible to reliably estimate their frequency.

OVERDOSAGE

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displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

Acute Toxicity Several cases of overdosage have been reported, some leading to death. Oral LD ₅₀‘s (mg/kg): mice, 1158-2460; rats, 3090-4670. Signs and Symptoms Potential signs and symptoms associated with overdosage with metoprolol tartrate are bradycardia, hypotension, bronchospasm, myocardial infarction, cardiac failure and death. Management There is no specific antidote. In general, patients with acute or recent myocardial infarction may be more hemodynamically unstable than other patients and should be treated accordingly (see WARNINGS, Myocardial Infarction). On the basis of the pharmacologic actions of metoprolol tartrate, the following general measures should be employed:
Elimination of the Drug:
Gastric lavage should be performed. Other clinical manifestations of overdose should be managed symptomatically based on modern methods of intensive care.
Hypotension:
Administer a vasopressor, e.g., levarterenol or dopamine.
Bronchospasm:
Administer a beta₂-stimulating agent and/or a theophylline derivative.
Cardiac Failure:
Administer digitalis glycoside and diuretic. In shock resulting from inadequate cardiac contractility, consider administration of dobutamine, isoproterenol or glucagon.

DOSAGE AND ADMINISTRATION

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displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

Hypertension Individualize the dosage of metoprolol tartrate tablets. Metoprolol tartrate tablets should be taken with or immediately following meals. The usual initial dosage of metoprolol tartrate tablets is 100 mg daily in single or divided doses, whether used alone or added to a diuretic. Increase the dosage at weekly (or longer) intervals until optimum blood pressure reduction is achieved. In general, the maximum effect of any given dosage level will be apparent after 1 week of therapy. The effective dosage range of metoprolol tartrate tablets is 100-450 mg per day. Dosages above 450 mg per day have not been studied. While once-daily dosing is effective and can maintain a reduction in blood pressure throughout the day, lower doses (especially 100 mg) may not maintain a full effect at the end of the 24-hour period, and larger or more frequent daily doses may be required. This can be evaluated by measuring blood pressure near the end of the dosing interval to determine whether satisfactory control is being maintained throughout the day. Beta₁ selectivity diminishes as the dose of metoprolol tartrate is increased. Angina Pectoris The dosage of metoprolol tartrate tablets should be individualized. Metoprolol tartrate tablets should be taken with or immediately following meals. The usual initial dosage of metoprolol tartrate tablets is 100 mg daily, given in two divided doses. Gradually increase the dosage at weekly intervals until optimum clinical response has been obtained or there is pronounced slowing of the heart rate. The effective dosage range of metoprolol tartrate tablets is 100-400 mg per day. Dosages above 400 mg per day have not been studied. If treatment is to be discontinued, gradually decrease the dosage over a period of 1-2 weeks (see WARNINGS). Myocardial Infarction
Early Treatment:
During the early phase of definite or suspected acute myocardial infarction, initiate treatment with metoprolol tartrate as soon as possible after the patient’s arrival in the hospital. Such treatment should be initiated in a coronary care or similar unit immediately after the patient’s hemodynamic condition has stabilized. Begin treatment in this early phase with the intravenous administration of three bolus injections of 5 mg of metoprolol tartrate each; give the injections at approximately 2-minute intervals. During the intravenous administration of metoprolol tartrate, monitor blood pressure, heart rate, and electrocardiogram. In patients who tolerate the full intravenous dose (15 mg), initiate metoprolol tartrate tablets, 50 mg every 6 hours, 15 minutes after the last intravenous dose and continue for 48 hours. Thereafter, the maintenance dosage is 100 mg twice daily (see Late Treatment below). Start patients who appear not to tolerate the full intravenous dose on metoprolol tartrate tablets either 25 mg or 50 mg every 6 hours (depending on the degree of intolerance) 15 minutes after the last intravenous dose or as soon as their clinical condition allows. In patients with severe intolerance, discontinue metoprolol tartrate (see WARNINGS).

HOW SUPPLIED

id: a34c52c6-797a-4429-9fc7-a892e544a498
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

NDC:50436-3155-1 60 TABLET, FILM COATED in a BOTTLE NDC:50436-3155-2 30 TABLET, FILM COATED in a BOTTLE NDC:50436-3155-4 180 TABLET, FILM COATED in a BOTTLE

METOPROLOL TARTRATE 25MG TABLET

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displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4