Metoprolol Tartrate Tablets USP, Revised: December 2008, Rx only, 174366

/Metoprolol Tartrate Tablets USP, Revised: December 2008, Rx only, 174366
Metoprolol Tartrate Tablets USP, Revised: December 2008, Rx only, 1743662018-09-06T09:12:40+00:00

Prescription Drug Name:

Metoprolol Tartrate Tablets USP, Revised: December 2008, Rx only, 174366

ID:

6e2fc3d3-a1c8-4f0b-a65d-441ed623fc3d

Code:

34391-3

DESCRIPTION


id: cbeda4c1-2e27-4141-8506-66037166c76c
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Metoprolol tartrate USP, is a selective beta1-adrenoreceptor blocking agent, available as 50 mg and 100 mg tablets for oral administration. Metoprolol tartrate USP is (±)-1-(Isopropylamino)-3-[p-(2-methoxyethyl)phenoxy]-2-propanol L-(+)-tartrate (2:1) salt, and its structural formula is: (C15H25NO3)2•C4H606 Metoprolol tartrate USP is a white, practically odorless, crystalline powder with a molecular weight of 684.82. It is very soluble in water; freely soluble in methylene chloride, in chloroform, and in alcohol; slightly soluble in acetone; and insoluble in ether. Inactive Ingredients: Tablets contain lactose anhydrous, microcrystalline cellulose, sodium starch glycolate, talc, povidone, magnesium stearate, hydroxypropyl methylcellulose, titanium dioxide, polyethylene glycol, and polysorbate 80. The 50 mg dosage strength also contains D&C Red No. 30 aluminum lake and the 100 mg dosage strength also contains FD&C Blue No. 2 aluminum lake.

CLINICAL PHARMACOLOGY


id: 644b531c-50c1-4a50-918b-2aaeceb3a22c
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1

Metoprolol tartrate is a beta-adrenergic receptor blocking agent. In vitro and in vivo animal studies have shown that it has a preferential effect on beta1 adrenoreceptors, chiefly located in cardiac muscle. This preferential effect is not absolute, however, and at higher doses, metoprolol also inhibits beta2 adrenoreceptors, chiefly located in the bronchial and vascular musculature. Clinical pharmacology studies have confirmed the beta-blocking activity of metoprolol in man, as shown by (1) reduction in heart rate and cardiac output at rest and upon exercise, (2) reduction of systolic blood pressure upon exercise, (3) inhibition of isoproterenol-induced tachycardia, and (4) reduction of reflex orthostatic tachycardia. Relative beta1 selectivity has been confirmed by the following: (1) In normal subjects, metoprolol is unable to reverse the beta2-mediated vasodilating effects of epinephrine. This contrasts with the effect of nonselective (beta1 plus beta2) beta blockers, which completely reverse the vasodilating effects of epinephrine, (2) In asthmatic patients, metoprolol reduces FEV1 and FVC significantly less than a nonselective beta blocker, propranolol, at equivalent beta1-receptor blocking doses. Metoprolol has no intrinsic sympathomimetic activity, and membrane-stabilizing activity is detectable only at doses much greater than required for beta blockade. Metoprolol crosses the blood-brain barrier and has been reported in the CSF in a concentration 78% of the simultaneous plasma concentration. Animal and human experiments indicate that metoprolol slows the sinus rate and decreases AV nodal conduction. In controlled clinical studies, metoprolol tartrate has been shown to be an effective antihypertensive agent when used alone or as concomitant therapy with thiazide-type diuretics, at dosages of 100-450 mg daily. In controlled, comparative, clinical studies, metoprolol has been shown to be as effective an antihypertensive agent as propranolol, methyldopa, and thiazide-type diuretics, and to be equally effective in supine and standing positions. The mechanism of the antihypertensive effects of beta-blocking agents has not been elucidated. However, several possible mechanisms have been proposed: (1) competitive antagonism of catecholamines at peripheral (especially cardiac) adrenergic neuron sites, leading to decreased cardiac output; (2) a central effect leading to reduced sympathetic outflow to the periphery; and (3) suppression of renin activity. By blocking catecholamine-induced increases in heart rate, in velocity and extent of myocardial contraction, and in blood pressure, metoprolol reduces the oxygen requirements of the heart at any given level of effort, thus making it useful in the long-term management of angina pectoris. However, in patients with heart failure, beta-adrenergic blockade may increase oxygen requirements by increasing left ventricular fiber length and end-diastolic pressure. Although beta-adrenergic receptor blockage is useful in the treatment of angina and hypertension, there are situations in which sympathetic stimulation is vital. In patients with severely damaged hearts, adequate ventricular function may depend on sympathetic drive. In the presence of AV block, beta blockage may prevent the necessary facilitating effect of sympathetic activity on conduction. Beta2-adrenergic blockage results in passive bronchial constriction by interfering with endogenous adrenergic bronchodilator activity in patients subject to bronchospasm and may also interfere with exogenous bronchodilators in such patients. In controlled clinical trials, metoprolol tartrate, administered two or four times daily, has been shown to be an effective antianginal agent, reducing the number of angina attacks and increasing exercise tolerance. The dosage used in these studies ranged from 100 mg to 400 mg daily. A controlled, comparative clinical trial showed that metoprolol was indistinguishable from propranolol in the treatment of angina pectoris. In a large (1,395 patients randomized), double-blind, placebo-controlled clinical study, metoprolol was shown to reduce 3-month mortality by 36% in patients with suspected or definite myocardial infarction. Patients were randomized and treated as soon as possible after their arrival in the hospital, once their clinical condition had stabilized and their hemodynamic status had been carefully evaluated. Subjects were ineligible if they had hypotension, bradycardia, peripheral signs of shock, and/or more than minimal basal rales as signs of congestive heart failure. Initial treatment consisted of intravenous followed by oral administration of metoprolol tartrate or placebo, given in a coronary care or comparable unit. Oral maintenance therapy with metoprolol or placebo was then continued for 3 months. After this double-blind period, all patients were given metoprolol and followed up to 1 year. The median delay from the onset of symptoms to the initiation of therapy was 8 hours in both the metoprolol and placebo treatment groups. Among patients treated with metoprolol, there were comparable reductions in 3-month mortality for those treated early (≤8 hours) and those in whom treatment was started later. Significant reductions in the incidence of ventricular fibrillation and in chest pain following initial intravenous therapy were also observed with metoprolol and were independent of the interval between onset of symptoms and initiation of therapy. The precise mechanism of action of metoprolol in patients with suspected or definite myocardial infarction is not known. In this study, patients treated with metoprolol received the drug both very early (intravenously) and during a subsequent 3-month period, while placebo patients received no beta-blocker treatment for this period. The study thus was able to show a benefit from the overall metoprolol regimen but cannot separate the benefit of very early intravenous treatment from the benefit of later beta-blocker therapy. Nonetheless, because the overall regimen showed a clear beneficial effect on survival without evidence of an early adverse effect on survival, one acceptable dosage regimen is the precise regimen used in the trial. Because the specific benefit of very early treatment remains to be defined however, it is also reasonable to administer the drug orally to patients at a later time as is recommended for certain other beta blockers.

HOW SUPPLIED


id: 55682a44-3892-4646-9e48-cde66f01c179
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Metoprolol Tartrate Tablets USP 50 mg—round, scored pink tablets embossed with Watson 462, supplied in bottles of 100 and 1000. Metoprolol Tartrate Tablets USP 100 mg—round, scored light blue tablets embossed with Watson 463, supplied in bottles of 100 and 1000. Store at 20°-25°C (68°-77°F). [See USP controlled room temperature.] Do not store above 30°C (86°F). Dispense in a tight, light-resistant container (USP). Protect from moisture. Manufactured By:
Watson Pharma Private Limited
Verna, Salcette Goa 403 722 INDIA
Distributed By:
Watson Pharma, Inc.

Corona, CA 92880 USA Revised: December 2008                        1208B
                                                                 174366

PACKAGE LABEL


id: f78d8309-0b76-4bf3-b7e8-fbdd8e71a37f
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

METOPROLOL 50MG LABEL IMAGE