Mechanism of Action

Metoprolol Tartrate Tablets USP is a beta1-selective (cardioselective) adrenergic receptor blocker. This preferential effect is not absolute, however, and at higher plasma concentrations, Metoprolol Tartrate Tablets USP also inhibits beta2-adrenoreceptors, chiefly located in the bronchial and vascular musculature.

Clinical pharmacology studies have demonstrated the beta-blocking activity of metoprolol, 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.

Hypertension

The mechanism of the antihypertensive effects of beta-blocking agents has not been fully 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.

Angina Pectoris

By blocking catecholamine-induced increases in heart rate, in velocity and extent of myocardial contraction and in blood pressure, Metoprolol Tartrate Tablets USP 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.

Myocardial Infarction

The precise mechanism of action of Metoprolol Tartrate Tablets USP in patients with suspected or definite myocardial infarction is not known.

Pharmacodynamics

Relative beta1 selectivity is demonstrated by the following: (1) In healthy subjects, Metoprolol Tartrate Tablets USP is unable to reverse the beta2-mediated vasodilating effects of epinephrine. This contrasts with the effect of nonselective (beta1 plus beta2) beta-blockers, which completely reverse the vasodilating effects of epinephrine. (2) In asthmatic patients, Metoprolol Tartrate Tablets USP reduces FEV1 and FVC significantly less than a nonselective beta-blocker, propranolol, at equivalent beta1-receptor blocking doses.

Metoprolol Tartrate Tablets USP has no intrinsic sympathomimetic activity, and membrane-stabilizing activity is detectable only at doses much greater than required for beta blockade. Animal and human experiments indicate that Metoprolol Tartrate Tablets USP slows the sinus rate and decreases AV nodal conduction.

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 effect after single oral doses of 20 mg, 50 mg and 100 mg occurred at 3.3 hours, 5.0 hours 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. When the drug was infused over a 10-minute period, in normal volunteers, maximum beta blockade was achieved at approximately 20 minutes. 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 Tartrate Tablets USP 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.

Absorption
The estimated oral bioavailability of immediate-release metoprolol is about 50% be- cause of pre-systemic metabolism which is saturable leading to non-proportionate increase in the exposure with increased dose.

Distribution
Metoprolol is extensively distributed with a reported volume of distribution of 3.2 to 5.6 L/kg. About 10% of metoprolol in plasma 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 following oral administration and CSF concentrations close to that observed in plasma have been reported. Metoprolol is not a significant P-glycoprotein substrate.

Metabolism
Metoprolol Tartrate Tablets USP is primarily metabolized by CYP2D6. Metoprolol is a racemic mixture of R- and S-enantiomers, and when administered orally, it exhibits stereoselective metabolism that is dependent on oxidation phenotype. CYP2D6 is absent (poor metabolizers) in about 8% of Caucasians and about 2% of most other populations. Poor CYP2D6 metabolizers exhibit several-fold higher plasma concentrations of Metoprolol Tartrate Tablets USP than extensive metabolizers with normal CYP2D6 activity thereby decreasing Metoprolol Tartrate Tablets USP’s cardioselectivity.

Elimination
Elimination of Metoprolol Tartrate Tablets USP is mainly by biotransformation in the liver. The mean elimination half-life of metoprolol is 3 to 4 hours; in poor CYP2D6 metabolizers the half-life may be 7 to 9 hours. Approximately 95% of the dose can be recovered in urine. In most subjects (extensive metabolizers), less than 5% of an oral dose and less than 10% of an intravenous dose are excreted as unchanged drug in the urine. In poor metabolizers, up to 30% or 40% of oral or intravenous doses, respectively, may be excreted unchanged; the rest is excreted by the kidneys as metabolites that appear to have no beta blocking activity. The renal clearance of the stereoisomers does not exhibit stereo-selectivity in renal excretion.

Geriatric Patients
The geriatric population may show slightly higher plasma concentrations of metoprolol as a combined result of a decreased metabolism of the drug in elderly population and a decreased hepatic blood flow. However, this increase is not clinically significant or therapeutically relevant.

Renal Impairment
The systemic availability and half-life of Metoprolol Tartrate Tablets USP in patients with renal failure do not differ to a clinically significant degree from those in normal subjects.

Hepatic Impairment
Since the drug is primarily eliminated by hepatic metabolism, hepatic impairment may impact the pharmacokinetics of metoprolol. The elimination half-life of metoprolol is considerably prolonged, depending on severity (up to 7.2 h).

Hypertension
In controlled clinical studies, Metoprolol Tartrate Tablets USP 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 Tartrate Tablets USP has been shown to be as effective an antihypertensive agent as propranolol, methyldopa and thiazide-type diuretics, to be equally effective in supine and standing positions.

Angina Pectoris
In controlled clinical trials, Metoprolol Tartrate Tablets USP, administered two or four times daily, has been shown to be an effective antianginal agent, reducing the number of angina attacks and increasing exercise tolerance. The dosage used in these studies ranged from 100 mg to 400 mg daily. A controlled, comparative, clinical trial showed that Metoprolol Tartrate Tablets USP was indistinguishable from propranolol in the treatment of angina pectoris.

Myocardial Infarction
In a large (1,395 patients randomized), double-blind, placebo-controlled clinical study, Metoprolol Tartrate Tablets USP 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 Tablets USP or placebo, given in a coronary care or comparable unit. Oral maintenance therapy with Metoprolol Tartrate Tablets USP or placebo was then continued for 3 months. After this double-blind period, all patients were given Metoprolol Tartrate Tablets USP 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 Tartrate Tablets USP and placebo treatment groups. Among patients treated with Metoprolol Tartrate Tablets USP, there were comparable reductions in 3-month mortality for those treated early (no more than 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 Tartrate Tablets USP and were independent of the interval between onset of symptoms and initiation of therapy.

In this study, patients treated with metoprolol received the drug both very early (intra-venously) 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.

Hypertension
Metoprolol Tartrate Tablets USP are indicated for the treatment of hypertension. They may be used alone or in combination with other antihypertensive agents.

Angina Pectoris
Metoprolol Tartrate Tablets USP are indicated in the long-term treatment of angina pectoris.

Myocardial Infarction
Metoprolol Tartrate Tablets USP are indicated in the treatment of hemodynamically stable patients with definite or suspected acute myocardial infarction to reduce cardiovascular mortality when used alone or in conjunction with intravenous Metoprolol Tartrate Tablets USP. Oral Metoprolol Tartrate Tablets USP therapy can be initiated after intravenous Metoprolol Tartrate Tablets USP therapy or, alternatively, oral treatment can begin within 3 to 10 days of the acute event (seeDOSAGE AND ADMINISTRATION ,CONTRAINDICATIONS and WARNINGS).

Hypertension and Angina
Metoprolol Tartrate Tablets USP are contraindicated in sinus bradycardia, heart block greater than first degree, cardiogenic shock, and overt cardiac failure (see WARNINGS).

Hypersensitivity to Metoprolol Tartrate Tablets USP and related derivatives, or to any of the excipients; hypersensitivity to other beta-blockers (cross-sensitivity between beta blockers can occur).

Sick-sinus syndrome.

Severe peripheral arterial circulatory disorders.

Myocardial Infarction
Metoprolol Tartrate Tablets USP is contraindicated in patients with a heart rate of less than 45 beats/min; second- and third-degree heart block; significant first-degree heart block (P-R interval no less than 0.24 sec); systolic blood pressure less than 100 mmHg; or moderate to severe cardiac failure (see WARNINGS).

Drug Interactions

Catecholamine-Depleting Drugs
Catecholamine-depleting drugs (e.g., reserpine) may have an additive effect when given with beta-blocking agents or monoamine oxidase (MAO) inhibitors. Observe patients treated with Metoprolol Tartrate Tablets USP plus a catecholamine depletor for evidence of hypotension or marked bradycardia, which may produce vertigo, syncope, or postural hypotension. In addition, possibly significant hypertension may theoretically occur up to 14 days following discontinuation of the concomitant administration with an irreversible MAO inhibitor.

Digitalis Glycosides and Beta-Blockers
Both digitalis glycosides and beta blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia. Monitor heart rate and PR interval.

Calcium Channel Blockers
Concomitant administration of a beta-adrenergic antagonist with a calcium channel blocker may produce an additive reduction in myocardial contractility because of negative chronotropic and inotropic effects.

CYP2D6 Inhibitors
Potent inhibitors of the CYP2D6 enzyme may increase the plasma concentration of Metoprolol Tartrate Tablets USP which would mimic the pharmacokinetics of CYP2D6 poor metabolizer (see PHARMACOKINETICS section). Increase in plasma concentrations of metoprolol would decrease the cardioselectivity of metoprolol. Known clinically significant potent 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; antiretrovirals such as ritonavir; antihistamines such as diphenhydramine; antimalarials such as hydroxychloroquine or quinidine; antifungals such as terbinafine.

Hydralazine
Concomitant administration of hydralazine may inhibit presystemic metabolism of metoprolol leading to increased concentrations of metoprolol.

Alpha-Adrenergic Agents
Antihypertensive effect of alpha-adrenergic blockers such as guanethidine, betanidine, reserpine, alpha-methyldopa or clonidine may be potentiated by beta-blockers including Metoprolol Tartrate Tablets USP. Beta-adrenergic blockers may also potentiate the postural hypotensive effect of the first dose of prazosin, probably by preventing reflex tachycardia. On the contrary, beta adrenergic blockers may also potentiate the hypertensive response to withdrawal of clonidine in patients receiving concomitant clonidine and beta-adrenergic blocker. If a patient is treated with clonidine and Metoprolol Tartrate Tablets USP concurrently, and clonidine treatment is to be discontinued, stop Metoprolol Tartrate Tablets USP several days before clonidine is withdrawn. Rebound hypertension that can follow withdrawal of clonidine may be increased in patients receiving concurrent beta-blocker treatment.

Ergot Alkaloid
Concomitant administration with beta-blockers may enhance the vasoconstrictive action of ergot alkaloids.

Dipyridamole
In general, administration of a beta-blocker should be withheld before dipyridamole testing, with careful monitoring of heart rate following the dipyridamole injection.

Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term studies in animals have been conducted to evaluate carcinogenic potential. In a 2-year study in rats at three oral dosage levels of up to 800 mg/kg per day, there was no increase in the development of spontaneously occurring benign or malignant neoplasms of any type. The only histologic changes that appeared to be drug related were an increased incidence of generally mild focal accumulation of foamy macrophages in pulmonary alveoli and a slight increase in biliary hyperplasia. In a 21-month study in Swiss albino mice at three oral dosage levels of up to 750 mg/kg per day, benign lung tumors (small adenomas) occurred more frequently in female mice receiving the highest dose than in untreated control animals. There was no increase in malignant or total (benign plus malignant) lung tumors, or in the overall incidence of tumors or malignant tumors. 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 mutagenicity tests performed (a dominant lethal study in mice, chromosome studies in somatic cells, a Salmonella/mammalian-microsome mutagenicity test, and a nucleus anomaly test in somatic interphase nuclei) were negative.

Reproduction toxicity studies in mice, rats and rabbits did not indicate teratogenic potential for metoprolol tartrate. Embryotoxicity and/or fetotoxicity in rats and rabbits were noted starting at doses of 50 mg/kg in rats and 25 mg/kg in rabbits, as demonstrated by increases in preimplantation loss, decreases in the number of viable fetuses per dose, and/or decreases in neonatal survival. High doses were associated with some maternal toxicity, and growth delay of the offspring in utero, which was reflected in minimally lower weights at birth. The oral NOAELs for embryo-fetal development in mice, rats and rabbits were considered to be 25, 200, and 12.5 mg/kg. This corresponds to dose levels that are approximately 0.3 times, 4 times, and 0.5 times, respectively, when based on surface area, 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 dose levels of 3.5 mg/kg in rats (a dose that is only 0.1 times the human dose, when based on surface area), although other studies have shown no effect of metoprolol tartrate on reproductive performance in male rats.

Pregnancy Category C

Upon confirming the diagnosis of pregnancy, women should immediately inform the doctor.

Metoprolol Tartrate Tablets USP has been shown to increase postimplantation loss and decrease neonatal survival in rats at doses up to 11 times the maximum daily human dose of 450 mg, when based on surface area. Distribution studies in mice confirm exposure of the fetus when Metoprolol Tartrate Tablets USP is administered to the pregnant animal. These limited animal studies do not indicate direct or indirect harmful effects with respect to teratogenicity (see CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY).

There are no adequate and well-controlled studies in pregnant women. The amount of data on the use of metoprolol in pregnant women is limited. The risk to the fetus/ mother is unknown. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Metoprolol Tartrate Tablets USP is excreted in breast milk in a very small quantity. An infant consuming 1 liter of breast milk daily would receive a dose of less than 1 mg of the drug.

Fertility

The effects of Metoprolol Tartrate Tablets USP on the fertility of human have not been studied.

Metoprolol Tartrate Tablets USP showed effects on spermatogenesis in male rats at a therapeutic dose level, but had no effect on rates of conception at higher doses in animal fertility studies (see CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY).

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical trials of Metoprolol Tartrate Tablets USP in hypertension did not include sufficient numbers of elderly patients to determine whether patients over 65 years of age differ from younger subjects in their response to Metoprolol Tartrate Tablets USP. Other reported clinical experience in elderly hypertensive patients has not identified any difference in response from younger patients.

In worldwide clinical trials of Metoprolol Tartrate Tablets USP in myocardial infarction, where approximately 478 patients were over 65 years of age (0 over 75 years of age), no age-related differences in safety and effectiveness were found. Other reported clinical experience in myocardial infarction has not identified differences in response between the elderly and younger patients. However, greater sensitivity of some elderly individuals taking Metoprolol Tartrate Tablets USP cannot be categorically ruled out. Therefore, in general, it is recommended that dosing proceed with caution in this population.

Hypertension and Angina

Most adverse effects have been mild and transient.

Central Nervous System
Tiredness and dizziness have occurred in about 10 of 100 patients. Depression has been reported in about 5 of 100 patients. Mental confusion and short-term memory loss have been reported. Headache, nightmares, and insomnia have also been reported.

Cardiovascular
Shortness of breath and bradycardia have occurred in approximately 3 of 100 patients. Cold extremities; arterial insufficiency, usually of the Raynaud type; palpitations; congestive heart failure; peripheral edema; and hypotension have been reported in about 1 of 100 patients. Gangrene in patients with preexisting severe peripheral circulatory disorders has also been reported very rarely (see CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS).

Respiratory
Wheezing (bronchospasm) and dyspnea have been reported in about 1 of 100 patients (see WARNINGS). Rhinitis has also been reported.

Gastrointestinal
Diarrhea has occurred in about 5 of 100 patients. Nausea, dry mouth, gastric pain, constipation, flatulence, and heartburn have been reported in about 1 of 100 patients. Vomiting was a common occurrence. 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.

Hypersensitive Reactions
Pruritus or rash have occurred in about 5 of 100 patients. Very rarely, photosensitivity and worsening of psoriasis has been reported.

Miscellaneous
Peyronie’s disease has been reported in fewer than 1 of 100,000 patients. Musculoskeletal pain, blurred vision, and tinnitus have also been reported.

There have been rare reports of reversible alopecia, agranulocytosis, and dry eyes. Discontinuation of the drug should be considered if any such reaction is not otherwise explicable. There have been very rare reports of weight gain, arthritis, and retroperitoneal fibrosis (relationship to Metoprolol Tartrate Tablets USP has not been definitely established).

The oculomucocutaneous syndrome associated with the beta-blocker practolol has not been reported with Metoprolol Tartrate Tablets USP.

Central Nervous System
Tiredness has been reported in about 1 of 100 patients. Vertigo, sleep disturbances, hallucinations, headache, dizziness, visual disturbances, confusion, and reduced libido have also been reported, but a drug relationship is not clear.

Cardiovascular
In the randomized comparison of Metoprolol Tartrate Tablets USP and placebo described in the CLINICAL PHARMACOLOGY section, the following adverse reactions were reported:

Respiratory
Dyspnea of pulmonary origin has been reported in fewer than 1 of 100 patients

Gastrointestinal
Nausea and abdominal pain have been reported in fewer than 1 of 100 patients.

Dermatologic
Rash and worsened psoriasis have been reported, but a drug relationship is not clear.

Miscellaneous
Unstable diabetes and claudication have been reported, but a drug relationship is not clear.

Potential Adverse Reactions
A variety of adverse reactions not listed above have been reported with other beta-adrenergic blocking agents and should be considered potential adverse reactions to Metoprolol Tartrate Tablets USP.

Central Nervous System
Reversible mental depression progressing to catatonia; an acute reversible syndrome characterized by disorientation for time and place, short-term memory loss, emo- tional lability, slightly clouded sensorium, and decreased performance on neuropsy- chometrics.

Cardiovascular
Intensification of AV block (see CONTRAINDICATIONS).

Hematologic
Agranulocytosis, nonthrombocytopenic purpura and thrombocytopenic purpura.

Hypersensitive Reactions
Fever combined with aching and sore throat, laryngospasm and respiratory distress.

Post-Marketing Experience
The following adverse reactions have been reported during post-approval use of Metoprolol Tartrate Tablets USP: confusional state, an increase in blood triglycerides and a decrease in High Density Lipoprotein (HDL). Because these reports are from a population of uncertain size and are subject to confounding factors, it is not possible to reliably estimate their frequency.

Acute Toxicity

Several cases of overdosage have been reported, some leading to death.

Oral LD50’s (mg/kg): mice, 1,158 to 2,460; rats, 3,090 to 4,670.

Signs and Symptoms

Potential signs and symptoms associated with overdosage with Metoprolol Tartrate Tablets USP are bradycardia, hypotension, bronchospasm, myocardial infarction, cardiac failure and death.

Management
There is no specific antidote.

In general, patients with acute or recent myocardial infarction may be more hemodynamically unstable than other patients and should be treated accordingly (see WARNINGS, MYOCARDIAL INFARCTION).

On the basis of the pharmacologic actions of Metoprolol Tartrate Tablets USP, the following general measures should be employed:

Elimination of the Drug

Gastric lavage should be performed.

Other clinical manifestations of overdose should be managed symptomatically based on modern methods of intensive care.

Hypotension

Administer a vasopressor, e.g., levarterenol or dopamine.

Bronchospasm

Administer a beta2-stimulating agent and/or a theophylline derivative.

Cardiac Failure

Administer digitalis glycoside and diuretic. In shock resulting from inadequate cardiac contractility, consider administration of dobutamine, isoproterenol or glucagon.

Hypertension
Individualize the dosage of Metoprolol Tartrate Tablets USP. Metoprolol Tartrate Tablets USP should be taken with or immediately following meals.

The usual initial dosage of Metoprolol Tartrate Tablets USP is 100 mg daily in single or divided doses, whether used alone or added to a diuretic. Increase the dosage at weekly (or longer) intervals until optimum blood pressure reduction is achieved. In general, the maximum effect of any given dosage level will be apparent after one week of therapy. The effective dosage range of Metoprolol Tartrate Tablets USP 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. Beta1 selectivity diminishes as the dose of Metoprolol Tartrate Tablets USP is increased.

Angina Pectoris

The dosage of Metoprolol Tartrate Tablets USP should be individualized. Metoprolol Tartrate Tablets USP should be taken with or immediately following meals.

The usual initial dosage of Metoprolol Tartrate Tablets USP is 100 mg daily, given in two divided doses. Gradually increase the dosage at weekly intervals until optimum clinical response has been obtained or there is pronounced slowing of the heart rate. The effective dosage range of Metoprolol Tartrate Tablets USP is 100 mg to 400 mg per day. Dosages above 400 mg per day have not been studied. If treatment is to be discontinued, gradually decrease the dosage over a period of 1 to 2 weeks (see WARNINGS).

Myocardial Infarction

Special Populations

Method of Administration

For oral treatment, the tablets should be swallowed unchewed with a glass of water. Metoprolol Tartrate Tablets USP should always be taken in standardized relation with meals. If the physician asks the patient to take Metoprolol Tartrate Tablets USP either before breakfast or with breakfast, then the patient should continue taking Metoprolol Tartrate Tablets USP with the same schedule during the course of therapy.