Metoprolol tartrate, USP, is a selective β1-adrenoceptor blocker available in 25, 50 and 100 mg tablets for oral administration. Metoprolol tartrate is (±)-1-(isopropylamino)-3-[p-(2-methoxyethyl)phenoxy]-2-propanol (2:1) dextrotartrate.
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, chloroform and alcohol. sparingly soluble in acetone. and insoluble in ether.
Inactive ingredients. Tablets contain colloidal silicon dioxide, hydroxypropylmethylcellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate, povidone, sodium starch glycollate, talc and titanium dioxide.
Mechanism of action:
Metoprolol tartrate is a beta-selective (cardioselective) adrenergic receptor blocker. However, this preferential effect is not absolute and, at higher plasma concentrations, metoprolol tartrate also inhibits β2-adrenergic receptors located mainly in bronchial and vascular muscles.
Clinical pharmacological studies have demonstrated the beta-blocking effect of metoprolol, as demonstrated by (1) reduction in heart rate and cardiac output at rest and during exercise, (2) reduction in systolic blood pressure during exercise, (3) inhibition of tachycardia and (4) reduction of postural reflex tachycardia.
hypertension
The mechanism of the antihypertensive effect of beta-blockers is not fully understood. However, several possible mechanisms have been proposed: (1) competitive antagonism of catecholamines at peripheral (particularly cardiac) sites of adrenergic neurons, resulting in decreased cardiac output; (2) a central effect leading to decreased sympathetic outflow to the periphery; and (3) suppression of renin activity.
angina pectoris
By inhibiting catecholamine-induced increases in heart rate, the rate and extent of myocardial contraction, and blood pressure, metoprolol tartrate reduces the oxygen demand of the heart at any level of exercise, making it useful in the long-term treatment of angina pectoris.
Heart attack
The exact mechanism of action of metoprolol tartrate in patients with confirmed or suspected myocardial infarction is unknown.
Pharmacodynamics
The relative beta1 selectivity is evidenced by the following: (1) In healthy subjects, metoprolol tartrate is unable to reverse the beta2-mediated vasodilatory effects of epinephrine. This contrasts with the effects of non-selective beta-blockers (beta 1 plus beta 2), which completely reverse the vasodilator effects of adrenaline. (2) In asthmatic patients, metoprolol tartrate reduces FEV1 and FVC significantly less than a non-selective β-blocker, propranolol, at equivalent doses of β1 receptor blockade. Metoprolol tartrate does not have intrinsic sympathomimetic activity and its membrane stabilizing effect is only detectable at doses well above those required for the beta-blocker. Animal and human studies indicate that metoprolol tartrate decreases venous rhythm and decreases AV conduction.
A significant beta-blocking effect (measured by the reduction in heart rate during exercise) occurs within one hour of oral administration and its duration is dose-dependent. For example, in normal subjects, a single oral dose of 20, 50, and 100 mg had a 50 percent reduction in peak effect at 3.3, 5.0, and 6.4 hours, respectively. After repeated oral administration of 100 mg twice daily, a significant reduction in systolic blood pressure was evident after 12 hours. When the drug was infused over a period of 10 minutes, peak beta-blockade was reached in about 20 minutes in normal volunteers. The maximum equivalent beta-blocking effect is obtained with oral and intravenous doses in a ratio of approximately 2.5:1.
There is a linear relationship between logarithmic plasma levels and heart rate reduction during exercise. However, the antihypertensive effect does not seem to be related to plasma levels. Due to the variable plasma levels achieved with a given dose and the lack of a consistent dose relationship of antihypertensive effect, selection of the appropriate dose requires individual titration.
In several studies in patients with acute myocardial infarction, intravenous administration followed by oral metoprolol tartrate resulted in decreases in heart rate, systolic blood pressure and cardiac output. Stroke volume, diastolic blood pressure and end-diastolic pressure in the pulmonary artery remained unchanged.
In patients with angina pectoris, the plasma concentration measured after one hour is linearly related to the oral dose in the range of 50-400 mg. Exercise heart rate and systolic blood pressure decrease in relation to the logarithm of the oral dose of metoprolol. Increases in exercise capacity and reductions in left ventricular ischemia were also significantly related to the logarithm of the oral dose.
pharmacokinetics
Absorption: The estimated oral bioavailability of immediate-release metoprolol is approximately 50%, as presystemic metabolism is saturated, resulting in a disproportionate increase in exposure with increasing dose.
Distribution: Metoprolol is widely distributed with a reported volume of distribution of 3.2 to 5.6 L/kg. About 10% of plasma metoprolol is bound to serum albumin. Metoprolol is known to cross the placenta and is found in breast milk. Metoprolol is also known to cross the blood-brain barrier after oral administration and CSF concentrations approaching plasma concentrations have been reported. Metoprolol is not an important P-glycoprotein substrate.
Metabolism: Metoprolol tartrate is primarily metabolized by CYP2D6. Metoprolol is a racemic mixture of R and S enantiomers and when administered orally it exhibits a stereoselective metabolism dependent on the oxidation phenotype. CYP2D6 (poor metabolisers) is absent in about 8% of Caucasians and about 2% in most other populations. CYP2D6 poor metabolisers have plasma concentrations of metoprolol tartrate several times higher than extensive metabolisers with normal CYP2D6 activity, thus reducing the cardioselectivity of metoprolol tartrate.
Elimination: Metoprolol tartrate is eliminated primarily by biotransformation in the liver. The mean elimination half-life of metoprolol is 3 to 4 hours. in CYP2D6 poor metabolisers, the half-life can be 7 to 9 hours. About 95% of the dose can be recovered in the urine. In most individuals (extensive metabolisers), less than 5% of an oral dose and less than 10% of an intravenous dose is excreted in the urine as unchanged drug. In patients with impaired metabolism, up to 30% and 40% of oral and intravenous doses, respectively, may be excreted unchanged. The remainder is excreted by the kidneys as metabolites that do not appear to have beta-blocking activity. Renal clearance of stereoisomers does not show stereoselectivity in renal elimination.
special populations
Geriatric Patients: Slightly higher plasma concentrations of metoprolol may occur in the geriatric population due to reduced drug metabolism in the elderly and reduced hepatic perfusion. However, this increase is neither clinically significant nor therapeutically relevant.
Renal Impairment: Systemic exposure and half-life of metoprolol tartrate in patients with renal impairment do not differ clinically significantly from those in healthy subjects.
Hepatic impairment: As the drug is primarily eliminated by hepatic metabolism, hepatic impairment may affect the pharmacokinetics of metoprolol. Depending on the severity, the half-life of metoprolol is significantly prolonged (up to 7.2 hours).
Clinical studies:
hypertension
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 in doses ranging from 100 to 450 mg per day. In comparative controlled clinical studies, metoprolol tartrate has been shown to be as effective an antihypertensive agent as propranolol, methyldopa, and thiazide-type diuretics, and is equally effective in the supine and standing positions.
angina pectoris
In controlled clinical trials, metoprolol tartrate, given twice or four times a day, has been shown to be an effective antianginal agent, reducing the number of angina attacks and increasing exercise tolerance. The dose used in these studies ranged from 100 to 400 mg per day. A comparative controlled clinical study showed that metoprolol tartrate was indistinguishable from propranolol in the treatment of angina pectoris.
Heart attack
In a large (1,395 patients randomized), double-blind, placebo-controlled clinical trial, metoprolol tartrate 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 at the hospital, after stabilization of the clinical picture and careful assessment of the hemodynamic state. Subjects were ineligible if they had hypotension, bradycardia, peripheral evidence of shock, and/or background noise greater than the minimum as evidence of heart failure. Initial treatment consisted of intravenous administration followed by oral administration of metoprolol tartrate or placebo in a coronary ward or equivalent unit. Maintenance oral therapy with metoprolol tartrate or placebo was continued for 3 months. After this double-blind period, all patients received metoprolol tartrate and were followed for up to one year.
The median delay from symptom onset to treatment initiation was 8 hours in both metoprolol tartrate and placebo treated groups. In patients treated with metoprolol tartrate, there was a comparable reduction in 3-month mortality in patients treated early (≤ 8 hours) and later. Significant reductions in the incidence of ventricular fibrillation and chest pain after initial IV therapy were also seen with metoprolol tartrate and were independent of the time between symptom onset and initiation of therapy.
In this study, metoprolol-treated patients received the drug early (intravenously) and during a 3-month follow-up period, while placebo patients did not receive beta-blocker treatment during this period. Thus, the study was able to demonstrate the benefit of the entire metoprolol regimen, but it cannot separate the benefit of very early intravenous therapy from the benefit of later beta-blocker therapy. However, as the overall regimen showed a clear positive effect on survival and there was no evidence of an early adverse effect on survival, the precise dosing regimen used in the study is an acceptable dosing regimen. However, as the specific benefit of early treatment remains unclear, it also makes sense to administer the drug orally to patients later on, as is recommended for some other beta-blockers.
hypertension
Metoprolol tartrate tablets are indicated for the treatment of hypertension. They can be used alone or in combination with other antihypertensive medications.
angina pectoris
Metoprolol tartrate tablets are indicated for the long-term treatment of angina pectoris.
Heart attack
Metoprolol tartrate injections and tablets are indicated for the treatment of hemodynamically stable patients with established or suspected acute myocardial infarction to reduce cardiovascular mortality. Treatment with intravenous metoprolol tartrate can be started as soon as the patient's clinical condition allows (see DOSAGE AND ADMINISTRATION, CONTRAINDICATIONS and WARNINGS). Alternatively, treatment can be started within 3 to 10 days of the acute event (see DOSAGE AND ADMINISTRATION).
hypertension and angina pectoris
Metoprolol tartrate is contraindicated in sinus bradycardia, heart block greater than first degree, cardiogenic shock and overt heart failure (see WARNINGS).
Hypersensitivity to metoprolol and related derivatives or to any of the excipients. Hypersensitivity to other beta-blockers (cross-sensitivity between beta-blockers may occur);
Sick-Sinus-Syndrom.
Serious disorders of peripheral arterial circulation.
Heart attack
Metoprolol is contraindicated in patients with a heart rate < 45 beats/minute. 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 heart failure (see WARNINGS).
hypertension and angina pectoris
Heart failure: Sympathetic stimulation is an important component of supporting circulatory function in heart failure, and the beta-blocker carries the potential risk of further reducing myocardial contractility and causing more severe failure
In patients without a history of heart failure: Prolonged myocardial depression with beta-blockers may in some cases lead to heart failure. At the first sign or symptom of impending heart failure, the patient should be completely scanned and/or given a diuretic. The reaction must be carefully monitored. If heart failure persists despite adequate digitalization and diuretic therapy, metoprolol should be discontinued.
Ischemic heart disease: Exacerbations of angina and, in some cases, myocardial infarction have occurred after abrupt withdrawal of certain beta-blockers. When stopping chronic metoprolol therapy, especially in patients with ischemic heart disease, the dose should be reduced over 1 to 2 weeks and the patient carefully monitored. If angina pectoris significantly worsens or acute coronary insufficiency develops, treatment with metoprolol should be resumed immediately, at least temporarily, and other appropriate measures to treat unstable angina pectoris should be instituted. Patients should be warned against interrupting or discontinuing treatment without medical advice. As coronary artery disease is common and may go unrecognized, it may be advisable not to stop metoprolol abruptly, even in patients treated for hypertension alone.
Bronchospastic Diseases: PATIENTS WITH BRONCHOSPASTICS DISEASES GENERALLY SHOULD NOT USE BETA-BLOCKERS, including metoprolol tartrate. However, due to its relative beta1 selectivity, metoprolol may be used with caution in patients with bronchospastic disease who are unresponsive or intolerant of other antihypertensive therapies. As beta1 selectivity is not absolute, a beta2 stimulating agent should be administered concurrently and the lowest possible dose of metoprolol tartrate should be used. In such cases, it would be advisable to start metoprolol at lower doses three times daily rather than larger doses twice daily to avoid the higher plasma levels associated with the longer dosing interval (see DOSAGE AND ADMINISTRATION).
Major Surgery: Chronic beta-blocker therapy should not be routinely discontinued prior to major surgery. However, the heart's reduced ability to respond to reflex adrenergic stimuli may increase the risk of general anesthesia and surgical procedures.
Diabetes and hypoglycemia: Beta-blockers can mask the tachycardia that occurs with hypoglycemia, but other symptoms such as dizziness and sweating may not be significantly affected.
Pheochromocytoma: When metoprolol is used in pheochromocytoma, it should be given in combination with an alpha-blocker and only after initiation of alpha-blocker treatment. Administration of beta-blockers alone in pheochromocytoma has been associated with a paradoxical increase in blood pressure due to attenuation of beta-mediated vasodilation in skeletal muscle.
Thyrotoxicosis: Beta-adrenergic blockade may mask some clinical signs (eg, tachycardia) of hyperthyroidism. Avoid abruptly discontinuing the beta-blocker, as this can lead to a thyroid storm.
Heart attack
Heart Failure: Sympathetic stimulation is an important component of supporting circulatory function, and the beta-blocker carries the potential risk of suppressing myocardial contractility and inducing or exacerbating minimal heart failure.
During treatment with metoprolol, the patient's hemodynamic status should be carefully monitored. If heart failure occurs or persists despite appropriate therapy, metoprolol should be discontinued.
Bradycardia: Metoprolol causes a slow heart rate in most patients. This reduction is greatest in patients with high baseline heart rates and lowest in patients with low baseline heart rates. Acute myocardial infarction (especially inferior infarction) can lead to a significant decrease in venous rhythm. If the atrial rate drops to < 40 beats/minute, particularly if accompanied by signs of decreased cardiac output, atropine (0.25 to 0.5 mg) should be given intravenously. If atropine therapy is unsuccessful, metoprolol should be discontinued and careful implantation of isoproterenol or a pacemaker should be considered.
AV Block: Metoprolol slows AV conduction and can cause significant first (P-R intervals ≥ 0.26 sec), second, or third degree heart block. Acute myocardial infarction also causes heart block.
If heart block occurs, metoprolol should be discontinued and atropine (0.25 to 0.5 mg) administered intravenously. If atropine treatment is unsuccessful, careful implantation of isoproterenol or a pacemaker should be considered.
Hypotension: If hypotension occurs (systolic blood pressure ≤ 90 mmHg), metoprolol should be discontinued and the patient's hemodynamic status and extent of myocardial damage should be carefully evaluated. Invasive monitoring of the central vein, pulmonary capillary cone, and blood pressure may be necessary. Appropriate fluid therapy, positive inotropic agents, antipulsatile balloon stimulation, or other methods of treatment should be used. If hypotension is associated with sinus bradycardia or atrioventricular block, treatment should aim to reverse these (see above).
Generally
Start with a low dose and slowly titrate the dose in patients with hepatic impairment.
information for patients
Patients should be instructed to take metoprolol regularly and continuously as directed, during or immediately after meals. If a dose is missed, the patient should only take the next scheduled dose (no doubling up). Patients should not discontinue metoprolol without consulting their physician.
Patients should be advised to (1) avoid driving cars, machines, or other tasks that require attention until the patient's response to metoprolol treatment is established; (2) Consult physician if breathing difficulty occurs. (3) Before any surgery, tell your doctor or dentist that you are taking metoprolol.
Interactions with other drugs
Catecholamine-depleting drugs: Catecholamine-depleting drugs (eg, reserpine) may have an additive effect when given with beta-blockers or monoamine oxidase (MAO) inhibitors. Monitor patients treated with metoprolol tartrate plus a catecholamine-lowering agent for signs of hypotension or marked bradycardia that may lead to dizziness, syncope, or orthostatic hypotension. In addition, potentially significant hypertension can theoretically occur up to 14 days after discontinuation of concomitant irreversible MAOIs.
Digitalis glycosides and beta-blockers: Both digitalis glycosides and beta-blockers slow AV conduction and lower heart rate. Concomitant use may increase the risk of bradycardia. Monitor heart rate and PR interval.
Calcium Channel Blockers: Co-administration of a beta-adrenergic antagonist with a calcium channel blocker may result in a cumulative decrease in myocardial contractility due to adverse chronotropic and inotropic effects.
Risk of anaphylactic reaction: When taking beta-blockers, patients with a history of severe anaphylactic reactions to various allergens may respond better to repeated exposures, whether accidental, diagnostic or therapeutic. These patients may not respond to the usual doses of adrenaline used to treat the allergic reaction.
General anesthetics: Certain inhalational anesthetics may potentiate the cardiodepressant effects of beta-blockers (see WARNINGS, Major Surgery).
CYP2D6 Inhibitors: Potent inhibitors of the CYP2D6 enzyme may increase metoprolol tartrate plasma concentrations, mimicking the pharmacokinetics of the CYP2D6 poor metaboliser (see Pharmacokinetics section). Increasing metoprolol plasma concentrations would decrease the cardioselectivity of metoprolol. Clinically important known strong inhibitors of CYP2D6 are antidepressants such as fluvoxamine, fluoxetine, paroxetine, sertraline, bupropion, clomipramine and desipramine. Antipsychotics such as chlorpromazine, fluphenazine, haloperidol and thioridazine. Antiarrhythmics such as quinidine or propafenone. antiretroviral drugs such as ritonavir. Antihistamines such as diphenhydramine. Antimalarials such as hydroxychloroquine or quinidine. Antifungal drugs such as terbinafine.
Hydralazine: Concomitant administration of hydralazine may inhibit the presystemic metabolism of metoprolol, resulting in increased concentrations of metoprolol.
Alpha-Adrenergic Agents: The antihypertensive effects of alpha-adrenergic blockers such as guanethidine, bethanidine, reserpine, alpha-methyldopa, or clonidine may be potentiated by beta-blockers, including metoprolol tartrate. Beta-blockers may also potentiate the antihypertensive effect of the first dose of prazosin, possibly by preventing reflex tachycardia. On the other hand, beta-blockers may also potentiate the hypertensive response to clonidine withdrawal in patients receiving clonidine and a beta-blocker concomitantly. If a patient is being treated concurrently with clonidine and metoprolol tartrate and clonidine therapy is discontinued, discontinue use of metoprolol tartrate a few days before discontinuing clonidine. Rebound hypertension that may occur after clonidine discontinuation may be exacerbated in patients receiving concomitant beta-blocker therapy.
Ergot alkaloid: Concomitant use with beta-blockers may potentiate the vasoconstrictive effects of ergot alkaloids
Dipyridamole: In general, the administration of a β-blocker should be withheld before the dipyridamole test and the heart rate carefully monitored after the dipyridamole injection.
Carcinogenesis, mutagenesis, impaired fertility
Long-term animal studies were performed to assess carcinogenic potential. In a 2-year study in rats with three oral doses of up to 800 mg/kg per day, there was no increase in the spontaneous development of benign or malignant neoplasms of any type. The only histologic changes considered drug-related appear to be an increased incidence of a generally mild focal accumulation of foamy macrophages in the alveoli and a slight increase in biliary hyperplasia. In a 21-month study in Swiss albino mice given three oral doses of up to 750 mg/kg daily, benign lung tumors (small adenomas) occurred in female mice given the higher dose than in untreated controls. There was no increase in malignant or total lung tumors (benign plus malignant) or in the overall incidence of tumors or malignancies. This 21-month study was repeated in CD-1 mice and no statistically or biologically significant differences were observed between treated and control mice of either sex for any type of tumor.
All mutagenesis tests performed (dominant lethal study in mice, chromosome studies in somatic cells, Salmonella/mammalian microsomal mutagenesis test, and nuclear anomaly test in interphase somatic nuclei) were negative.
Reproductive toxicity studies in mice, rats and rabbits revealed no teratogenic potential for metoprolol tartrate. Embryotoxicity and/or embryotoxicity in rats and rabbits was observed at doses of 50 mg/kg in rats and 25 mg/kg in rabbits, as shown by an increase in pre-implantation loss, a decrease in the number of viable embryos per dose and/or reduced survival rate of newborns. High doses were associated with some maternal toxicity and retardation of offspring growth in utero, reflected in somewhat lower birth weights. Oral NOAELs for fetal development in mice, rats, and rabbits were considered to be 25, 200, and 12.5 mg/kg. This corresponds to approximately 0.3, 4 and 0.5 times the dose based on the surface area of the maximum human oral dose (8 mg/kg/day) of metoprolol tartrate. Metoprolol tartrate has been associated with reversible adverse effects on spermatogenesis, starting at oral doses of 3.5 mg/kg in rats (a dose that is only 0.1 times the human dose when surface area is considered), although others studies have not demonstrated an effect of metoprolol tartrate on reproductive performance in male rats.
pregnancy category C
After confirming the diagnosis of pregnancy, the woman should inform the doctor immediately.
Metoprolol has been shown to increase postimplantation loss and reduce neonatal survival in rats at doses up to 11 times the maximum human daily dose of 450 mg when administered at the surface. Distribution studies in mice confirm fetal exposure when metoprolol is administered to pregnant animals. These limited animal studies do not indicate direct or indirect harmful effects in terms of teratogenicity (see Carcinogenicity, Mutagenicity, Impairment of Fertility).
There are no adequate and well-controlled studies in pregnant women. There are limited amount of data from the use of metoprolol in pregnant women. The risk to the fetus/mother is unknown. As animal reproduction studies are not always indicative of human response, this drug should not be used during pregnancy unless clearly necessary.
nursing mother
Metoprolol passes into breast milk in very small amounts. A child who drinks 1 liter of breast milk per day receives a dose of less than 1 mg of the drug.
Fertility: The effects of metoprolol tartrate on human fertility have not been studied.
Metoprolol tartrate showed effects on spermatogenesis in male rats at therapeutic dose, but had no effect on conception rate in animal fertility studies at higher doses (see Carcinogenesis, Mutagenesis, Impairment of Fertility).
pediatric use
Safety and efficacy in pediatric patients have not been established.
geriatric use
Clinical trials of Metoprolol Tartrate USP in hypertension did not include sufficient numbers of elderly people to determine whether patients over 65 years of age differ in their response to Metoprolol Tartrate from younger subjects. Other reported clinical experiences in elderly hypertensive patients found no differences in response compared to younger patients.
In global clinical studies of metoprolol tartrate in myocardial infarction, involving approximately 478 patients over 65 years of age (0 over 75 years), no age-related differences in safety and efficacy were identified. Other reported clinical experiences in myocardial infarction have not identified differences in response between elderly and younger patients. However, increased sensitivity in some elderly people receiving metoprolol tartrate cannot be categorically excluded. Therefore, it is generally recommended that caution be exercised when administering the dose in this patient population.
hypertension and angina pectoris
Most side effects were mild and transient.
Central Nervous System: About 10 out of 100 patients experience tiredness and dizziness. Depression has been reported in about 5 out of 100 patients. Mental confusion and short-term memory loss have been reported. Headaches, nightmares and insomnia have also been reported.
Cardiovascular: Dyspnea and bradycardia occurred in about 3 of 100 patients. Cold extremities? arterial insufficiency, usually Raynaud's type. palpitations; cardiac insufficiency? peripheral edema; and hypotension have been reported in about 1 in 100 patients. Gangrene has also been reported very rarely in patients with pre-existing severe peripheral circulatory disorders. (see CONTRAINDICATIONS, WARNINGS and PRECAUTIONS.)
Respiratory System: Wheezing (bronchospasm) and shortness of breath have been reported in approximately 1 in 100 patients (see WARNINGS). Rhinitis has also been reported.
Gastrointestinal: Diarrhea has occurred in about 5 out of 100 patients. Nausea, dry mouth, stomach pain, constipation, gas and heartburn have been reported in about 1 in 100 patients. Vomiting was common. Post-marketing experience shows very rare reports of hepatitis, jaundice and non-specific liver dysfunction. There have also been isolated reports of increases in transaminases, alkaline phosphatase and lactate dehydrogenase.
Hypersensitivity reactions: Itching or rash occurred in about 5 out of 100 patients. Photosensitivity and worsening of psoriasis have been reported very rarely.
Others: Peyronie's disease has been reported in less than 1 in 100,000 patients. Musculoskeletal pain, blurred vision and tinnitus have also been reported.
There have been rare reports of reversible alopecia, agranulocytosis and dry eye. Discontinuation of the drug should be considered if such a reaction cannot be otherwise explained. Very rarely, weight gain, arthritis and retroperitoneal fibrosis have been reported (relationship to metoprolol has not been definitively established).
Oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with metoprolol.
Heart attack
Central Nervous System: Fatigue has been reported in about 1 in 100 patients. Dizziness, difficulty sleeping, hallucinations, headache, dizziness, visual disturbances, confusion and decreased libido have also been reported, but the association with drugs is unclear.
Respiratory System: Dyspnoea of pulmonary origin has been reported in less than 1 in 100 patients.
Gastrointestinal: Nausea and abdominal pain have been reported in less than 1 in 100 patients.
Dermatologic: Rash and worsening of psoriasis have been reported, but the association with drugs is unclear.
Other: Unstable diabetes and claudication have been reported, but the association with drugs is unclear.
possible side effects
Several side effects not listed above have been reported with other beta-blockers and should be considered as possible side effects of metoprolol.
Central Nervous System: Reversible mental depression leading to catatonia. an acute reversible syndrome characterized by disorientation to time and place, short-term memory loss, emotional lability, mild sensory blindness, and impaired neuropsychometric performance.
Cardiovascular: increased AV block (see CONTRAINDICATIONS).
Hematologic: agranulocytosis, non-thrombocytopenic purpura, thrombocytopenic purpura.
Hypersensitivity reactions: fever associated with sore and sore throat, laryngospasm and shortness of breath.
aftermarket experience
The following side effects have been reported with post-marketing use of metoprolol tartrate: confusion, increased blood triglycerides, and decreased high-density lipoprotein (HDL). As these reports come from a population of uncertain size and are subject to confounding factors, it is not possible to reliably estimate their frequency.
acute toxicity
Several cases of overdose have been reported, some resulting in death.
Oral LD50 (mg/kg): camundongos, 1158 to 2460; moments, 3090 to 4670;
Signs and symptoms
Possible signs and symptoms of metoprolol overdose include bradycardia, hypotension, bronchospasm, myocardial infarction, heart failure, and death.
Management
There is no specific antidote.
In general, patients with a current or recent myocardial infarction may be more hemodynamically unstable than other patients and should be treated accordingly (see WARNINGS, Myocardial Infarction).
Due to the pharmacological action of metoprolol, the following general measures should be taken:
Drug elimination: Gastric lavage should be performed.
Other clinical manifestations of overdose should be treated symptomatically based on modern intensive care methods.
Hypotension: A vasopressor should be administered, e.g. B. Levaterenol or dopamine.
Bronchospasm: A β2-stimulating factor and/or a theophylline derivative should be administered.
Heart failure: digitalis glycoside and diuretic should be administered. In shock due to insufficient cardiac contractility, administration of dobutamine, isoproterenol, or glucagon may be considered.
hypertension
The dosage of metoprolol tartrate tablets should be individualized. Metoprolol tartrate tablets should be taken with or immediately after meals.
The usual starting dose of metoprolol tartrate tablets is 100 mg daily in single or divided doses, alone or in addition to a diuretic. Dosage may be increased at weekly (or longer) intervals until optimal blood pressure reduction is achieved. In general, the maximum effect of a given dose will be seen after one week of treatment. The effective dosage range of metoprolol tartrate tablets is 100 to 450 mg per day. Doses above 450 mg per day have not been studied. Although once-daily dosing is effective and may maintain blood pressure reduction throughout the day, lower doses (particularly 100 mg) may not maintain full effect beyond 24 hours and higher or more frequent daily doses may be required. This can be assessed by measuring blood pressure near the end of the dosing interval to determine whether satisfactory control is being maintained throughout the day. Beta1 selectivity decreases with increasing dose of metoprolol.
angina pectoris
The dosage of metoprolol tartrate tablets should be individualized. Metoprolol tartrate tablets should be taken with or immediately after meals.
The usual starting dose of metoprolol tartrate tablets is 100 mg per day divided into two doses. The dose may be gradually increased at weekly intervals until an optimal clinical response is achieved or a marked deceleration of heart rate occurs. The effective dosage range of metoprolol tartrate tablets is 100 to 400 mg per day. Doses above 400 mg per day have not been studied. If treatment has to be stopped, the dose should be reduced over 1 to 2 weeks (see WARNINGS).
Heart attack
early treatment
In the early phase of a confirmed or suspected acute myocardial infarction, treatment with metoprolol tartrate may be started as soon as possible after the patient's arrival at the hospital. Such treatment should be initiated in a coronary ward or similar department as soon as the patient's haemodynamic status has stabilized.
Treatment at this early stage should begin with three intravenous bolus injections of metoprolol tartrate 5 mg each. Injections should be given approximately 2 minutes apart. During intravenous administration of metoprolol, blood pressure, heart rate and electrocardiogram should be carefully monitored.
In patients who can tolerate the full intravenous dose (15 mg), metoprolol tartrate tablets 50 mg every 6 hours should be started 15 minutes after the last intravenous dose and continued for 48 hours. Thereafter, patients should receive a maintenance dose of 100 mg twice daily (see Delayed treatment below).
Patients who cannot tolerate the full intravenous dose should start taking metoprolol tartrate 25 mg or 50 mg tablets every 6 hours (depending on the degree of intolerance) 15 minutes after the last intravenous dose or as soon as their clinical condition allows. Metoprolol therapy should be discontinued in patients with severe intolerance (see WARNINGS).
delayed treatment
Patients with contraindications to treatment in the early stages of suspected or confirmed myocardial infarction, patients who apparently cannot tolerate full early treatment, and patients in whom the physician wants to delay treatment for other reasons should start taking metoprolol tartrate tablets ( 100). 2 mg twice a day as soon as your clinical condition allows. Treatment should be continued for at least 3 months. Although the efficacy of metoprolol beyond 3 months has not been conclusively demonstrated, data from studies with other beta-blockers suggest that treatment should be continued for 1 to 3 years.
special populations
Pediatric Patients: Pediatric studies have not been conducted. The safety and efficacy of metoprolol tartrate in pediatric patients have not been established.
Renal impairment: No dose adjustment of metoprolol tartrate is required in patients with renal impairment.
Hepatic Impairment: Metoprolol tartrate blood levels are likely to increase significantly in patients with hepatic impairment. Therefore, metoprolol tartrate should be started at low doses and carefully titrated gradually according to clinical response.
Geriatric Patients (> 65 years): In general, a low starting dose should be used in elderly patients, since decreased hepatic, renal, or cardiac function is more common and comorbidities or other drug therapies are present.
Administration type:
For oral treatment, the tablets should be swallowed whole with a glass of water. Metoprolol tartrate should always be taken in a standardized proportion with meals. If the doctor tells the patient to take metoprolol tartrate before breakfast or with breakfast, the patient should continue taking metoprolol tartrate at the same time throughout the treatment.
NDC: 51655-584-25
MFG: 57664-167-58
Metoprololtartrato 100 mg
60 pills
Nur Rx
Very#:
Exp. Given away:
Each tablet contains Metoprolol Tartrate, USP 100 MG
Dosage: For complete prescribing information, see
Store at 68 to 77 degrees Fahrenheit.
Store in a tight, light-resistant container. Protect from moisture.
Keep this and all medicines out of the reach of children.
Manufactured by Sun Pharma Laboratories Ltd. Dadra 396 191 India
Distributed by Caraco Pharmaceutical Laboratories, Ltd Detroit, MI 48202
Very#
Repackaged by Northwind Pharmaceuticals, Indianapolis, IN 46256
NDC: 51655-584-52
MFG: 57664-167-58
Metoprololtartrato 100 mg
30 pills
Nur Rx
Very#:
Exp. Given away:
Each tablet contains Metoprolol Tartrate, USP 100 MG
Dosage: For complete prescribing information, see
Store at 68 to 77 degrees Fahrenheit.
Store in a tight, light-resistant container. Protect from moisture.
Keep this and all medicines out of the reach of children.
Manufactured by Sun Pharma Laboratories Ltd. Dadra 396 191 India
Distributed by Caraco Pharmaceutical Laboratories, Ltd Detroit, MI 48202
Very#
Repackaged by Northwind Pharmaceuticals, Indianapolis, IN 46256
