Beta-Adrenergic Receptor Blocking Agent
Action And Clinical Pharmacology: Metoprolol is a b-adrenergic receptor-blocking agent. In vitro and in vivo animal studies have shown that it has a preferential effect on the b1-adrenoreceptors, chiefly located in cardiac muscle. This preferential effect is not absolute, however, and at higher doses, metoprolol also inhibits b2-adrenoreceptors, chiefly located in the bronchial and vascular musculature. Metoprolol has no membrane-stabilizing or partial agonism (intrinsic sympathomimetic activities). It is used in the treatment of hypertension, angina pectoris and to reduce mortality in patients with myocardial infarction.
The mechanism of the antihypertensive effect has not been established. Among the factors that may be involved are: a) competitive ability to antagonize catecholamine-induced tachycardia at the b-receptor sites in the heart, thus decreasing heart rate, cardiac contractility and cardiac output; b) inhibition of renin release by the kidneys; c) inhibition of the vasomotor centres.
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, b-adrenergic receptor blockade may increase oxygen requirements by increasing left ventricular fiber length and end-diastolic pressure (preload).
The mechanisms involved in reducing mortality in patients with acute myocardial infarction are not fully understood.
Pharmacokinetics: In humans, absorption of metoprolol is rapid and complete. Plasma levels following oral administration, however, approximate 50% of levels following i.v. administration, indicating about 50% first-pass metabolism.
Intersubject plasma levels achieved are highly variable after oral administration, although they show good reproducibility within each individual. Peak plasma concentrations are attained after approximately 1.5 to 2 hours with conventional metoprolol formulations, and after approximately 4 to 5 hours with slow-release formulations. Upon repeated oral administration, the percentage of the dose systemically available is higher than after a single dose and also increases dose dependently. Ingestion with food may raise the systemic availability of an oral dose by approximately 20 to 40%. Only a small fraction of the drug (about 12%) is bound to human serum albumin. Elimination is mainly by biotransformation in the liver, and the plasma half-life averages 3.5 hours (range: 1 to 9 hours). The total clearance rate of an i.v. dose is approximately 1 L/min and the protein binding rate is approximately 10%. 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; however metabolite excretion is impaired. Since the resulting metabolite accumulation has no effect on the b-blocking effects, no reduction in dosage is usually needed in patients with chronic renal failure.
Liver impairment may increase metoprolol bioavailability and reduce total clearance.
Pharmacodynamics: Significant beta-blocking effect (as measured by reduction of exercise heart rate) occurs within 1 hour after oral administration, and its duration is dose-related. For example, a 50% reduction of the maximum effect after single oral doses of 20, 50, and 100 mg occurred at 3.3, 5.0 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.
Pharmacokinetic and Pharmacodynamic Relationship: Following i.v. administration of metoprolol, the half-life of the distribution phase is approximately 12 minutes; the urinary recovery of unchanged drug is approximately 10%. When the drug was infused over a 10-minute period, in normal volunteers, maximum b-blockade was achieved at approximately 20 minutes. Doses of 5 mg and 15 mg yielded a maximal reduction in exercise-induced heart rate of approximately 10% and 15%, respectively. The effect on exercise heart rate decreased linearly with time at the same rate for both doses, and disappeared at approximately 5 hours and 8 hours for the 5 mg and 15 mg doses, respectively.
Equivalent maximal b-blocking effect is achieved with oral and i.v. 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, i.v. 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.
The SR formulation produced lower peak metoprolol plasma concentrations than the regular tablets in studies with volunteers. Between 4 to 6 hours both concentration curves were similar. During the 8- to 24-hour period concentrations were higher after the SR tablets.
Indications And Clinical Uses: Hypertension: Metoprolol is indicated for mild or moderate hypertension. Usually combined with other antihypertensive agents (thiazide diuretics), it may be tried alone when the physician judges that a beta-blocker rather than a diuretic, should be the initial treatment.
Combining metoprolol with a diuretic or peripheral vasodilator has been found to be compatible and generally more effective than metoprolol alone. Limited experience with other antihypertensive agents has not shown evidence of incompatibility with metoprolol.
Metoprolol is not recommended for the emergency treatment of hypertensive crises.
Angina Pectoris: Metoprolol is indicated for the long-term treatment of angina pectoris due to ischemic heart disease.
Myocardial Infarction: Metoprolol is indicated in the treatment of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality.
Treatment with i.v. metoprolol can be initiated as soon as the patient’s clinical condition allows (see Dosage, Contraindications and Warnings).
Alternatively, in patients with proven myocardial infarction, oral treatment can begin within 3 to 10 days of the acute event (see Dosage). Data are not available as to whether benefit would ensue if the treatment is initiated later.
Clinical trials have shown that patients with unconfirmed myocardial infarction received no benefit from early drug therapy.
Contra-Indications: Metoprolol should not be used in the presence of: known hypersensitivity to metoprolol and derivatives, Lopresor components; sinus bradycardia; sick sinus syndrome; second and third degree A-V block; right ventricular failure secondary to pulmonary hypertension; overt heart failure; cardiogenic shock; severe peripheral arterial circulatory disorders; anesthesia with agents that produce myocardial depression (e.g., ether); the i.v. form is also contraindicated in the presence of asthma and other obstructive respiratory diseases (for oral treatment, see Precautions, Bronchospastic Diseases).
Manufacturers’ Warnings In Clinical States: Cardiac Failure: Special caution should be exercised when administering metoprolol to patients with a history of heart failure. Sympathetic stimulation is a vital component supporting circulatory function in congestive heart failure, and inhibition with b-blockade always carries the potential hazard of further depressing myocardial contractility and precipitating cardiac failure. The positive inotropic action of digitalis may be reduced by the negative inotropic effect of metoprolol when the two drugs are used concomitantly. The effects of b-blockers and digitalis are additive in depressing A-V conduction. This also applies to combinations with calcium-antagonists of the verapamil type or some antiarrhythmics (see Drug Interactions).
In patients without a history of cardiac failure, continued depression of the myocardium over a period of time can, in some cases, lead to cardiac failure and/or hypotension (systolic blood pressure 90 mmHg). Therefore, at the first sign or symptom of impending cardiac failure, patients should be fully digitalized and/or given a diuretic and the response observed closely. If cardiac failure continues, despite adequate digitalization and diuretic therapy, metoprolol therapy should be reduced or withdrawn.
Abrupt Cessation of Therapy: Patients with angina should be warned against abrupt discontinuation of metoprolol. There have been no reports of severe exacerbation of angina and of myocardial infarction or ventricular arrhythmias in patients with angina pectoris, following abrupt discontinuation of beta-blocker therapy. The last 2 complications may occur with or without preceding exacerbation of angina pectoris. Therefore, when discontinuation of metoprolol is planned in patients with angina pectoris or previous myocardial infarction, the dosage should be reduced gradually over a period of about 2 weeks. The patient should be carefully observed. The same frequency of administration should be maintained. In situations of greater urgency, metoprolol therapy should be discontinued stepwise and with closer observation. If angina markedly worsens or acute coronary insufficiency develops, it is recommended that treatment with metoprolol be reinstituted promptly, at least temporarily.
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 is prudent not to discontinue metoprolol therapy abruptly even in patients treated only for hypertension.
Oculomucocutaneous Syndrome: Various skin rashes and conjunctival xerosis have been reported with b-blockers, including metoprolol. Oculomucocutaneous syndrome, a severe syndrome whose signs include conjunctivitis sicca and psoriasiform rashes, otitis, and sclerosing serositis, has occurred with the chronic use of one b-adrenergic receptor-blocking agent (practolol). This syndrome has not been observed with metoprolol or any other such agent. However, physicians should be alert to the possibility of such reactions and should discontinue treatment in the event they occur.
Severe Sinus Bradycardia: Severe sinus bradycardia may occur after b1-adrenergic receptor blockade with metoprolol because of unopposed vagal activity. Very rarely a pre-existing A-V conduction disorder of moderate degree may become aggravated, possibly leading to A-V block. In such cases, dosage should be reduced or gradually withdrawn. Atropine, isoproterenol or dobutamine should be considered in patients with acute myocardial infarction.
Thyrotoxicosis: Although metoprolol has been used successfuly for the symptomatic (adjuvant) therapy of thyrotoxicosis, possible deleterious effects from long-term use of metoprolol have not been adequately appraised. Beta-blockade may mask the clinical signs of continuing hyperthyroidism or its complications, and give a false impression of improvement. Therefore, abrupt withdrawal of metoprolol may be followed by an exacerbation of the symptoms of hyperthyroidism, including thyroid storm.
Myocardial Infarction Patients – Additional Warnings: Acute Intervention: During acute intervention in myocardial infarction, i.v. metoprolol should only be used by experienced staff under circumstances where resuscitation and monitoring equipment is available.
Cardiac Failure: Depression of the myocardium with metoprolol may lead to cardiac failure (see general Warnings). Special caution should be exercised when administering metoprolol to patients with a history of cardiac failure or those with minimal cardiac reserve. Should failure occur, treatment should be as described in Warnings.
Severe Sinus Bradycardia: Severe sinus bradycardia may occur with the use of metoprolol (see general Warnings). Acute myocardial infarction (particularly inferior infarcts) may significantly decrease sinus rate. If the rate falls below 40 beats/min, especially with signs of decreased cardiac output, administer atropine (0.25 to 0.5 mg) i.v. If atropine treatment is unsuccessful, discontinue metoprolol and consider cautious administration of isoproterenol or installation of a cardiac pacemaker.
A-V Conduction: Metoprolol slows A-V conduction and may produce significant first- (PR interval ³0.24 s), second-, or third-degree heart block. Acute myocardial infarction may also produce heart block. If heart block occurs, discontinue metoprolol and administer atropine (0.25 to 0.5 mg) i.v. If atropine treatment is unsuccessful, consider cautious administration of isoproterenol or installation of a cardiac pacemaker.
Hypotension: If hypotension (systolic blood pressure Â£90 mmHg) occurs, metoprolol should be discontinued, and the hemodynamic status of the patient and the extent of myocardial damage carefully assessed. Invasive monitoring of central venous, pulmonary capillary wedge, and arterial pressures may be required. Appropriate therapy with fluids, positive inotropic agents, balloon counterpulsation, or other treatment modalities should be instituted. If hypotension is associated with sinus bradycardia or A-V block, treatment should be directed at reversing these (see above).
Precautions: Bronchospastic Diseases: Patients with bronchospastic diseases should, in general, not receive b-blockers. Because of its relative b1-selectivity, however, metoprolol may be used with caution in patients with bronchospastic disease who do not respond to, or cannot tolerate, other antihypertensive treatment. Since b1-selectivity is not absolute, a b2-stimulating agent should be administered concomitantly, and the lowest possible dose of metoprolol 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 (see Dosage).
Because it is unknown to what extent b2-stimulating agents may exacerbate myocardial ischemia and the extent of infarction, these agents should not be used prophylactically in patients with proven or suspected acute myocardial infarction. If bronchospasm not related to congestive heart failure occurs, metoprolol should be discontinued. A theophylline derivative or a b2-agonist may be administered cautiously, depending on the clinical condition of the patient. Both theophylline derivatives and b2-agonists may produce serious cardiac arrhythmias.
Diabetes and Hypoglycemia: Metoprolol should be administered cautiously to spontaneously hypoglycemic or diabetic patients (especially those with labile diabetes) who are receiving insulin or oral hypoglycemic agents. b-adrenergic receptor blockers may mask the premonitory signs and symptoms of acute hypoglycemia.
Liver Function: Metoprolol should be used with caution in patients with impaired liver function. Liver function tests should be performed at regular intervals during long-term treatment (see Pharmacology, Pharmacokinetics).
Allergen Immunotherapy: There may be increased difficulty in treating an allergic type reaction in patients on b-blockers. In these patients, the reaction may be more severe due to pharmacologic effects of the b-blockers and problems with fluid changes. Epinephrine should be administered with caution since it may not have its usual effects in the treatment of anaphylaxis. On the one hand, larger doses of epinephrine may be needed to overcome the bronchospasm, while on the other, these doses can be associated with excessive alpha-adrenergic stimulation with consequent hypertension, reflex bradycardia and heart block and possible potentiation of bronchospasm. Alternatives to the use of large doses of epinephrine include vigorous supportive care such as fluids and the use of b-agonists including parenteral salbutamol or isoproterenol, to overcome bronchospasm and norepinephrine to overcome hypotension.
Patients Undergoing Surgery: Angina patients should be gradually withdrawn from metoprolol prior to elective surgery. Beta-blockade impairs cardiac response to b-andrenergically-mediated reflex stimuli. Protracted severe hypotension during anesthesia, and difficulty in restarting and maintaining the heartbeat in patients receiving b-blocking drugs, have been reported.
Follow the recommendations under Warnings, Abrupt Cessation of Therapy to avoid severe complications associated with abrupt withdrawal. All clinical and pharmacological effects should disappear within 48 hours of the last dose.
Since metoprolol is a competitive b-adrenergic receptor agonist inhibitor, its effects may be reversed, if necessary, by sufficient doses of agonists such as isoproterenol or dobutamine.
Peripheral Artery Disorders: Metoprolol may aggravate the symptoms of peripheral arterial circulatory disorders, mainly due to its blood pressure lowering effect.
Pheochromocytoma: Where a b-blocker is prescribed for a patient known to be suffering from a pheochromocytoma, an alpha-blocker should be given concomitantly.
Occupational Hazards, Reaction Time: b-blockers may adversely affect the patient’s reaction time. Patients should be advised to avoid operating automobiles and machinery or engaging in other tasks requiring alertness until the patient’s response to metoprolol therapy has been determined.
Pregnancy: Metoprolol crosses the placental barrier. Since metoprolol has not been studied in human pregnancy, the drug should not be given to pregnant women. The use of any drug in patients of child-bearing potential requires that the anticipated benefit be weighed against the possible hazards.
Lactation: Metoprolol is excreted in breast milk. If drug use is essential, patients should stop nursing.
Children: The safety and efficacy of metoprolol in children has not been established.
Geriatrics: Caution is indicated when using metoprolol in elderly patients. An excessively pronounced decrease in blood pressure or pulse rate may cause the blood supply to vital organs to fall to inadequate levels.
Drug Interactions: Antihypertensives: Metoprolol dosage should be adjusted to the individual requirements of the patient especially when used concomitantly with other antihypertensive agents (see Dosage).
MAO Inhibitors and Adrenergic Neuron-Blockers: Closely monitor patients receiving MAO inhibitors or catecholamine-depleting drugs (such as reserpine or guanethidine). The added b-adrenergic-blockade of metoprolol may excessively reduce sympathetic activity. Metoprolol should not be combined with other b-blockers.
Calcium Channel Blockers: As with other b-blockers, metoprolol should not be given together with verapamil type calcium-antagonists. However, in exceptional cases, when the physician considers concomitant use essential, such use should be instituted gradually in a hospital setting under careful supervision. Negative inotropic, dromotropic and chronotropic effects may occur when metoprolol is given together with calcium antagonists. Verapamil and diltiazem reduce metoprolol clearance.
Antiarrhythmic Agents: b-blockers may enhance the negative inotropic and negative dromotropic effect of antiarrhythmic agents such as quinidine and amiodarone.
Clonidine Withdrawal Syndrome: The hypertensive crisis which may follow clonidine withdrawal may be accentuated in the presence of b-blockade. Withdrawing the b-blocker several days before the clonidine may reduce the danger of rebound effects.
Oral Antidiabetics: The dosage of oral antidiabetics may have to be readjusted in patients receiving b-blockers (see Precautions).
NSAIDs: Concurrent treatment with indomethacin may decrease the antihypertensive effect of b-blockers.
Hepatic Enzyme-Inducers and Enzyme-Inhibitors: Hepatic enzyme-inducing and enzyme-inhibiting substances may exert an influence on the plasma level of metoprolol. The plasma concentration of metoprolol is lowered by rifampicin, and may be raised by cimetidine, ranitidine and propafenone.
Lidocaine: Metoprolol may reduce the clearance of lidocaine.
a-Adrenergic Stimulants (Cold Remedies, Nasal Drops): Exaggerated hypertensive responses can be produced when b-blockers are combined with a-adrenergic agonists.
Inhalation Anesthetics: b-blockers enhance the cardiodepression produced by certain anesthetics (see Precautions, Patients Undergoing Surgery).
Alcohol: Metoprolol may modify the pharmacokinetics (decrease the elimination rate) of alcohol.
Adverse Reactions: The most common adverse events reported are exertional tiredness, gastrointestinal disorders, and disturbances of sleep patterns. The most serious adverse events reported are congestive heart failure, bronchospasm and hypotension.
Reported adverse effects according to organ systems are:
Cardiovascular: secondary effects of decreased cardiac output which include: syncope, vertigo, light-headedness and postural hypotension; second and third degree A-V block (see Contraindications); congestive heart failure (see Warnings); severe bradycardia; lengthening of PR interval; sinus arrest; cardiac arrhythmias; palpitations; chest pains; hot flushes; edema; cold extremities; Raynaud’s phenomenon; claudication; gangrene in patients with pre-existing severe peripheral circulatory disorders.
In a placebo-controlled study in patients with acute myocardial infarction the incidence of the following cardiovascular reactions were as shown in Table I.
CNS: headache, dizziness, mental depression, light-headedness, vivid dreams/nightmares, vertigo, anxiety, decreased mental alertness, weakness, fatigue, sedation, somnolence or insomnia, hallucination, paresthesia, personality disorder.
Gastrointestinal: diarrhea, constipation, flatulence, nausea and vomiting, abdominal pain, heartburn, dryness of mouth, hepatitis.
Respiratory: shortness of breath, bronchospasm, status asthmaticus, wheezing, rhinitis.
Allergic/Dermatological (see Warnings): skin rash (exanthema, urticaria, psoriasiform and dystrophic skin lesions), sweating, pruritus, photosensitivity.
Ear, Eye, Nose and Throat (EENT): tinnitus, hearing difficulties when doses exceed those recommended, dry and/or itchy eyes, conjunctivitis, blurred vision and nonspecific visual disturbances.
Miscellaneous: muscle cramps, exertional tiredness, weight gain, loss of hair, decreased libido, Peyronie’s disease, arthritis.
Clinical Laboratory: The following laboratory parameters have been elevated on rare occasions: transaminases, BUN, alkaline phosphatase and bilirubin.
Hematology: Isolated cases of thrombocytopenia and leukopenia.
Symptoms And Treatment Of Overdose: Symptoms: The most common signs to be expected with overdosage of a b-adrenoreceptor agent are hypotension, bradycardia, congestive heart failure, bronchospasm and hypoglycemia. Atrioventricular block, cardiogenic shock and cardiac arrest may develop. In addition, impairment of consciousness (or even coma), nausea, vomiting and cyanosis may occur.
Concomitant ingestion of alcohol, antihypertensives, quinidine, or barbiturates aggravate the signs and symptoms.
The first manifestations of overdosage set in 20 minutes to 2 hours after drug administration.
Treatment: If overdosage occurs, in all cases therapy with metoprolol should be discontinued, the patient hospitalized and observed closely. Remove any drug remaining in the stomach by induction of emesis or gastric lavage. In addition, if required, the following therapeutic measures are suggested. 1. Bradycardia and Hypotension: Atropine 1 to 2 mg initially should be given i.v. If a satisfactory effect is not achieved, norepinephrine or dopamine may be administered after preceding treatment with atropine. (See Precautions concerning the use of epinephrine in patients.) In cases of hypoglycemia b-blocked glucagon (1 to 10 mg) can be administered. 2. Heart block (second or third degree): Isoproterenol or transvenous cardiac pacemaker. 3. Congestive heart failure: Conventional therapy. 4. Bronchospasm: I.V. aminophylline or a b2-agonist. 5. Hypoglycemia: I.V. glucose.
It should be remembered that metoprolol is a competitive antagonist of isoproterenol and hence large doses of isoproterenol can be expected to reverse many of the effects of excessive doses of metoprolol. However, the complications of excess isoproterenol, e.g. hypotension and tachycardia, should not be overlooked.
Dosage And Administration: Hypertension: Metoprolol is usually used in conjunction with other antihypertensive agents, particularly a thiazide diuretic, but may be used alone (see Indications).
The dose must always be adjusted to the individual requirements of the patient, in accordance with the following guidelines.
Metoprolol treatment should be initiated with doses of 50 mg b.i.d. If an adequate response is not seen after 1 week, dosage should be increased to 100 mg b.i.d. In some cases the daily dosage may need to be increased by further 100 mg increments at intervals of not less than 2 weeks up to a maximum of 200 mg b.i.d., which should not be exceeded. The usual maintenance dose is within the range of 100 to 200 mg daily.
When metoprolol is combined with another antihypertensive agent which is already being administered, metoprolol should be added initially at a dose of 50 mg b.i.d. After 1 or 2 weeks the daily dosage may be increased if required, in increments of 100 mg, at intervals of not less than 2 weeks, until adequate blood pressure control is obtained.
Angina Pectoris: The recommended dosage range is 100 to 400 mg/day in divided doses. Initiate treatment with 50 mg b.i.d. for the first week. If response is not adequate, the daily dosage should be increased by 100 mg for the next week. The usual maintenance dose is 200 mg/day. The need for further increases should be closely monitored at weekly intervals and the dosage increased in 100 mg increments to a maximum of 400 mg/day in 2 or 3 divided doses. A metoprolol dose of 400 mg/day should not be exceeded.
Slow-Release Tablets: Treatment must always be initiated and individual titration of dosage carried out using the regular tablets. The SR formulation may be preferred for maintenance because of the convenience of once-daily administration. Lopresor SR tablets should be taken in the morning and swallowed whole.
Lopresor SR 100 mg is intended for maintenance dosing in those patients requiring 100 mg metoprolol/day.
Lopresor SR 200 mg is intended for maintenance dosing in those patients requiring doses of 200 mg/day.
Tablet Residue in Feces: After the active substance has diffused out of the insoluble core of the Lopresor SR Tablet, the tablet residue is excreted in a softened form and may be found in the feces.
Therapy should be discontinued in patients if the heart rate drops below 45 or the systolic blood pressure drops below 100 mmHg.
Early Treatment: During the early phase of definite or suspected acute myocardial infarction, treatment with metoprolol 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 i.v. administration of 3 bolus injections of 5 mg each. The injections should be given at approximately 2-minute intervals. During the i.v. administration, blood pressure, heart rate, and ECG should be carefully monitored. If any of the injections are associated with adverse cardiovascular effects, i.v. administration should be stopped immediately and the patient should be observed carefully and appropriate therapy instituted.
In patients who tolerate the full i.v. dose (15 mg), metoprolol tablets, 50 mg every 6 hours, should be initiated 15 minutes after the last i.v. dose and continued for 48 hours. Thereafter, patients should receive a maintenance dosage of 100 mg twice daily (see Late Treatment).
Patients who appear not to tolerate the full i.v. dose should be started on either 25 or 50 mg every 6 hours (depending on the degree of intolerance) 15 minutes after the last i.v. dose or as soon as their clinical condition allows. In patients with severe intolerance, treatment with metoprolol should be discontinued (see Warnings).
Late Treatment (for proven myocardial infarction patients only): Patients with contraindications to treatment during the early phase of 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 tablets, 100 mg twice daily, as soon as their clinical condition allows. Treatment can begin within 3 to 10 days of the acute event. Therapy should be continued for at least 3 months. Although the efficacy of treatment beyond 6 months has not been conclusively established data from studies with other b-blockers suggest that the treatment should be continued for 1 to 3 years.
Note: Ampuls: Metoprolol ampuls are single dose ampuls intended for i.v. injection. All parenteral drug products should be inspected for particulate matter and discoloration prior to administration whenever solution and container permit. Discard any unused portion or solution with particulate matter or discoloration.
Availability And Storage: Ampuls: Each mL of aqueous, clear, injectable solution contains: metoprolol tartrate 1 mg. Also contains sodium chloride 9 mg. Alcohol-, bisulfite-, gluten-, lactose-, parabens- and tartrazine-free. Ampuls of 5 mL. Cartons of 5.
Protect ampuls from heat (store between 2 to 30°C) and light.
Tablets: 50 mg: Each light red, film-coated, capsule-shaped tablet embossed 51/51 and scored on one side and embossed Geigy on the other, contains: metoprolol tartrate 50 mg. Nonmedicinal ingredients: carnauba wax, cellulose compounds, lactose, magnesium stearate, peridone, polyethylene glycol, silicon dioxide, sodium carboxymethyl starch and talc. Energy: 1.05 kJ (0.25 kcal). Sodium:
100 mg: Each light blue, film-coated, capsule-shaped tablet embossed 71/71 and scored on one side and embossed Geigy on the other, contains: metoprolol tartrate 100 mg. Nonmedicinal ingredients: carnauba wax, cellulose compounds, lactose, magnesium stearate, peridone, polyethylene glycol, silicon dioxide, sodium carboxymethyl starch and talc. Energy: 1.05 kJ (0.25 kcal). Sodium:
Slow-Release Tablets: 100 mg: Each round, film-coated, orange-brown tablet, embossed GEIGY on one side and engraved on the other, contains: metoprolol tartrate 100 mg in a slow-release formulation. Nonmedicinal ingredients: carnauba wax, castor oil compounds, cellulose compounds, iron oxides, magnesium stearate, phosphates polysorbate, talc and titanium dioxide. Energy: 1.05 kJ (0.26 kcal). Alcohol-, bisulfite-, gluten-, lactose-, parabens-, sodium- and tartrazine-free. Bottles of 100 and 250.
200 mg: Each round, film-coated, light yellow tablet, embossed GEIGY on one side and CDC on the other, contains: metoprolol tartrate 200 mg in a slow-release formulation. Nonmedicinal ingredients: carnauba wax, castor oil compounds, cellulose compounds, iron oxides, magnesium stearate, phosphates polysorbate, talc and titanium dioxide. Energy: 1.05 kJ (0.26 kcal). Alcohol-, bisulfite-, gluten-, lactose-, parabens-, sodium- and tartrazine-free. Bottles of 100 and 250.
Protect tablets from heat (store between 2 and 30°C), light and humidity. (Shown in Product Recognition Section)
LOPRESOR® Novartis Pharmaceuticals Metoprolol Tartrate Beta-Adrenergic Receptor Blocking Agent
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