Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/1993
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Metoprolol Tartrate (Tablet, Film Coated)
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Hypertension: The dosage of metoprolol tartrate tablets should be individualized. Metoprolol tartrate tablets should be taken with or immediately following meals. The usual initial dosage is 100 mg daily in single or divided doses, whether used alone or added to a diuretic. The dosage may be increased 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 one week of therapy. The effective dosage range is 100 mg to 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. Betaselectivity diminishes as the dose of metoprolol is increased.<br/>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 is 100 mg daily, given in two divided doses. The dosage may be gradually increased at weekly intervals until optimum clinical response has been obtained or there is pronounced slowing of the heart rate. The effective dosage range is 100 mg to 400 mg per day. Dosages above 400 mg per day have not been studied. If treatment is to be discontinued, the dosage should be reduced gradually over a period of 1 to 2 weeks.<br/>Myocardial Infarction:<br/>Early Treatment: During the early phase of definite or suspected acute myocardial infarction, treatment with metoprolol tartrate tablets can be initiated 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. Treatment in this early phase should begin with the intravenous administration of three bolus injections of 5 mg of metoprolol tartrate each; the injections should be given at approximately 2 minute intervals. During the intravenous administration of metoprolol, blood pressure, heart rate, and electrocardiogram should be carefully monitored. In patients who tolerate the full intravenous dose (15 mg), metoprolol tartrate tablets, 50 mg every 6 hours, should be initiated 15 minutes after the last intravenous dose and continued for 48 hours. Thereafter, patients should receive a maintenance dosage of 100 mg twice daily (see Late Treatment below). Patients who appear not to tolerate the full intravenous dose should be started 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, treatment with metoprolol should be discontinued .<br/>Late Treatment: Patients with contraindications to treatment during the early phase of suspected or definite myocardial infarction, patients who appear not to tolerate the full early treatment, and patients in whom the physician wishes to delay therapy for any other reason should be started on metoprolol tartrate tablets, 100 mg twice daily, as soon as their clinical condition allows. Therapy should be continued for at least 3 months. Although the efficacy of metoprolol beyond 3 months has not been conclusively established, data from studies with other beta-blockers suggest that treatment should be continued for 1 to 3 years.
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| dailymed-instance:descripti... |
Metoprolol tartrate, USP is a selective beta-adrenoreceptor blocking agent, available as 25 mg, 50 mg and 100 mg tablets for oral administration. Metoprolol tartrate is (��)-1-(isopropylamino)-3-[p-2-methoxyethyl)phenoxy]-2-propanol (2:1) dextro-tartrate salt. Its structural formula is: Metoprolol tartrate 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. Each tablet for oral administration contains 25 mg, 50 mg or 100 mg of metoprolol tartrate and the following inactive ingredients: anhydrous lactose, colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, povidone, sodium lauryl sulfate, titanium dioxide and triacetin. In addition, the 50 mg product contains FD&C Blue No. 2 Aluminum Lake, D&C Red No. 27 Aluminum Lake and FD&C Red No. 40 Aluminum Lake and the 100 mg product contains FD&C Blue No. 2 Aluminum Lake as coloring agents.
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| dailymed-instance:clinicalP... |
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 betaadrenoreceptors, chiefly located in cardiac muscle. This preferential effect is not absolute, however, and at higher doses, metoprolol also inhibits betaadrenoreceptors, 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 betaselectivity has been confirmed by the following: (1) In normal subjects, metoprolol is unable to reverse the beta-mediated vasodilating effects of epinephrine. This contrasts with the effect of nonselective (betaplus beta) beta-blockers, which completely reverse the vasodilating effects of epinephrine. (2) In asthmatic patients, metoprolol reduces FEVand FVC significantly less than a nonselective beta-blocker, propranolol, at equivalent beta-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 mg to 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 blockade 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-blockade may prevent the necessary facilitating effect of sympathetic activity on conduction. Beta-adrenergic blockade 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 2 or 4 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 one 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.<br/>Pharmacokinetics: In man, absorption of metoprolol is rapid and complete. Plasma levels following oral administration, however, approximate 50% of levels following intravenous administration, indicating about 50% first-pass metabolism. Plasma levels achieved are highly variable after oral administration. Only a small fraction of the drug (about 12%) is bound to human serum albumin. Metoprolol is a racemic mixture of R- and S-enantiomers. Less than 5% of an oral dose of metoprolol is recovered unchanged in the urine; the rest is excreted by the kidneys as metabolites that appear to have no clinical significance. The systemic availability and half-life of metoprolol in patients with renal failure do not differ to a clinically significant degree from those in normal subjects. Consequently, no reduction in dosage is usually needed in patients with chronic renal failure. Metoprolol is extensively metabolized by the cytochrome P450 enzyme system in the liver. The oxidative metabolism of metoprolol is under genetic control with a major contribution of the polymorphic cytochrome P450 isoform 2D6 (CYP2D6). There are marked ethnic differences in the prevalence of the poor metabolizers (PM) phenotype. Approximately 7% of Caucasians and less than 1% Asian are poor metabolizers. Poor CYP2D6 metabolizers exhibit several-fold higher plasma concentrations of metoprolol than extensive metabolizers with normal CYP2D6 activity. The elimination half-life of metoprolol is about 7.5 hours in poor metabolizers and 2.8 hours in extensive metabolizers. However, the CYP2D6 dependent metabolism of metoprolol seems to have little or no effect on safety or tolerability of the drug. None of the metabolites of metoprolol contribute significantly to its beta-blocking effect. Significant beta-blocking effect (as measured by reduction of exercise heart rate) occurs within one hour after oral administration, and its duration is dose related. For example, a 50% reduction of the maximum registered effect after single oral doses of 20 mg, 50 mg and 100 mg occurred at 3.3, 5 and 6.4 hours, respectively, in normal subjects. After repeated oral dosages of 100 mg twice daily, a significant reduction in exercise systolic blood pressure was evident at 12 hours. Equivalent maximal beta-blocking effect is achieved with oral and intravenous doses in the ratio of approximately 2.5:1. There is a linear relationship between the log of plasma levels and reduction of exercise heart rate. However, antihypertensive activity does not appear to be related to plasma levels. Because of variable plasma levels attained with a given dose and lack of a consistent relationship of antihypertensive activity to dose, selection of proper dosage requires individual titration. In several studies of patients with acute myocardial infarction, intravenous followed by oral administration of metoprolol caused a reduction in heart rate, systolic blood pressure, and cardiac output. Stroke volume, diastolic blood pressure, and pulmonary artery end diastolic pressure remained unchanged. In patients with angina pectoris, plasma concentration measured at one hour is linearly related to the oral dose within the range of 50 mg to 400 mg. Exercise heart rate and systolic blood pressure are reduced in relation to the logarithm of the oral dose of metoprolol. The increase in exercise capacity and the reduction in left ventricular ischemia are also significantly related to the logarithm of the oral dose. In elderly subjects with clinically normal renal and hepatic function, there are no significant differences in metoprolol pharmacokinetics compared to young subjects.
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Metoprolol Tartrate Tablets, USP are available containing 25 mg, 50 mg or 100 mg of metoprolol tartrate, USP. The 25 mg tablets are white film-coated, round, scored tablets debossed with M over 18 on one side of the tablet and scored on the other side. They are available as follows: NDC 0378-0018-01bottles of 100 tabletsNDC 0378-0018-05bottles of 500 tablets The 50 mg tablets are pink film-coated, round, scored tablets debossed with M over 32 on one side of the tablet and scored on the other side. They are available as follows: NDC 0378-0032-01bottles of 100 tabletsNDC 0378-0032-10bottles of 1000 tablets The 100 mg tablets are light blue film-coated, round, scored tablets debossed with M over 47 on one side of the tablet and scored on the other side. They are available as follows: NDC 0378-0047-01bottles of 100 tabletsNDC 0378-0047-10bottles of 1000 tablets Store at 20��to 25��C (68��to 77��F). [See USP for Controlled Room Temperature.] Protect from moisture. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
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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, 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 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.<br/>Bronchospastic Diseases: PATIENTS WITH BRONCHOSPASTIC DISEASES SHOULD, IN GENERAL, NOT RECEIVE BETA-BLOCKERS. Because of its relative betaselectivity, however, metoprolol may be used with caution in patients with bronchospastic disease who do not respond to, or cannot tolerate, other antihypertensive treatment. Since betaselectivity is not absolute, a beta-stimulating agent should be administered concomitantly, and the lowest possible dose of metoprolol tartrate should be used. In these circumstances it would be prudent initially to administer 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.<br/>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, 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.<br/>Diabetes and Hypoglycemia: Metoprolol 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.<br/>Pheochromocytoma: In patients known to have, or suspected of having, a pheochromocytoma, metoprolol is contraindicated . If metoprolol is required, 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.<br/>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.
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dailymed-ingredient:anhydrous_lactose,
dailymed-ingredient:colloidal_silicon_dioxide,
dailymed-ingredient:croscarmellose_sodium,
dailymed-ingredient:hypromellose,
dailymed-ingredient:magnesium_stearate,
dailymed-ingredient:microcrystalline_cellulose,
dailymed-ingredient:polydextrose,
dailymed-ingredient:polyethylene_glycol,
dailymed-ingredient:povidone,
dailymed-ingredient:sodium_lauryl_sulfate,
dailymed-ingredient:titanium_dioxide,
dailymed-ingredient:triacetin
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Acute Toxicity: Several cases of overdosage have been reported, some leading to death. Oral LD's (mg/kg): mice, 1,158 to 2,460; rats, 3,090 to 4,670.<br/>Signs and Symptoms: Potential signs and symptoms associated with overdosage with metoprolol are bradycardia, hypotension, bronchospasm, and cardiac failure.<br/>Treatment: 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 . On the basis of the pharmacologic actions of metoprolol, the following general measures should be employed:<br/>Elimination of the Drug: Gastric lavage should be performed.<br/>Bradycardia: Atropine should be administered. If there is no response to vagal blockade, isoproterenol should be administered cautiously.<br/>Hypotension: A vasopressor should be administered, e.g., norepinephrine or dopamine.<br/>Bronchospasm: A beta-stimulating agent and/or a theophylline derivative should be administered.<br/>Cardiac Failure: A digitalis glycoside and diuretic should be administered. In shock resulting from inadequate cardiac contractility, administration of dobutamine, isoproterenol, or glucagon may be considered.
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Metoprolol Tartrate
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Metoprolol Tartrate (Tablet, Film Coated)
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Hypertension and Angina: Most adverse effects have been mild and transient.<br/>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.<br/>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.<br/>Respiratory: Wheezing (bronchospasm) and dyspnea have been reported in about 1 of 100 patients. Rhinitis has also been reported.<br/>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.<br/>Hypersensitive Reactions: Pruritus or rash have occurred in about 5 of 100 patients. Very rarely, photosensitivity and worsening of psoriasis have been reported.<br/>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.<br/>Myocardial Infarction:<br/>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.<br/>Cardiovascular: In the randomized comparison of metoprolol and placebo described in the CLINICAL PHARMACOLOGY section, the following adverse reactions were reported:<br/>Respiratory: Dyspnea of pulmonary origin has been reported in fewer than 1 of 100 patients.<br/>Gastrointestinal: Nausea and abdominal pain have been reported in fewer than 1 of 100 patients.<br/>Dermatologic: Rash and worsened psoriasis have been reported, but a drug relationship is not clear.<br/>Miscellaneous: Unstable diabetes and claudication have been reported, but a drug relationship is not clear.<br/>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.<br/>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.<br/>Cardiovascular: Intensification of AV block .<br/>Hematologic: Agranulocytosis, nonthrombocytopenic purpura, thrombocytopenic purpura.<br/>Hypersensitive Reactions: Fever combined with aching and sore throat, laryngospasm, and respiratory distress.
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Hypertension: Metoprolol tartrate tablets are indicated for the treatment of hypertension. They may be used alone or in combination with other antihypertensive agents.<br/>Angina Pectoris: Metoprolol tartrate tablets are indicated in the long-term treatment of angina pectoris.<br/>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. Treatment with intravenous metoprolol can be initiated as soon as the patient's clinical condition allows . Alternatively, treatment can begin within 3 to 10 days of the acute event.
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Metoprolol Tartrate
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