Metoprolol Tartrate Injection USP

5 mg/5 ml


For the use of a Registered Medical Practitioner or a Hospital or a Institution only. 

Metoprolol Tartrate Injection USP

Metoprolol  Tartrate  Injection  USP (Metoprolol Tartrate) is a cardioselective beta blocker. Chemically, Metoprolol Tartrate is (±)-1-(Isopropylamino)-3-[p-(2-methoxyethyl)phenoxy]-2-propanol l-(+)-tartrate (2:1) (salt). The molecular formula is (C15H25NO3 )2 · C4H6O6 and molecular weight is 684.81.


Its structural formula is :



Metoprolol  Tartrate  Injection  USP is a sterile, clear, colourless solution filled in ampoule of suitable size.

Each ml contains :
Metoprolol Tartrate USP                1 mg
Sodium Chloride USP                   9 mg
Water for Injection USP                   q.s.
Contains no preservatives.

Metoprolol is a beta1-selective (cardioselective) adrenergic receptor blocker. This preferential effect is not absolute, however, and at higher plasma concentrations, metoprolol 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,  reduction of systolic blood pressure upon exercise, inhibition of isoproterenol-induced tachycardia, and 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 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 in patients with suspected or definite myocardial infarction is not known.

Metoprolol is readily and completely absorbed from the gastrointestinal tract but is subject to considerable first-pass metabolism, with a bioavailability of about 50 %. Peak plasma concentrations vary widely and occur about 1.5 to 2 hours after a single oral dose. It is moderately lipid-soluble. Metoprolol is widely distributed; it crosses the blood-brain barrier and the placenta, and is distributed into breast milk. It is about 12 % bound to plasma protein. It is extensively metabolised in the liver, mainly by the cytochrome P450 isoenzyme CYP2D6, and undergoes oxidative deamination, O-dealkylation followed by oxidation, and aliphatic hydroxylation. The metabolites are excreted in the urine with only small amounts of unchanged metoprolol. The rate of metabolism by CYP2D6 is determined by genetic polymorphism; the half-life of metoprolol in fast hydroxylators is stated to be 3 to 4 hours, whereas in poor hydroxylators it is about 7 hours.

METOPROLOL  TARTRATE  INJECTION  USP is used to control arrhythmias. In surgery at induction or to control arrhythmias developing during anaesthesia. Early intervention within 12 hours of infarction.


Administration :

Method of administration :
Parenteral administration of Metoprolol  Tartrate  Injection  USP should be done in a setting with intensive monitoring.

The ampoule used in this product is equipped with O.P.C. (One Point Cut) opening system. No ampoule file is needed to open the ampoule. The neck of the ampoule is prescored at the point of constriction. A coloured dot on the ampoule head helps to orientate the ampoule. Take the ampoule and face the coloured dot. Let the solution at the head of the ampoule to flow down by shaking or a gentle stroke. The ampoule opens easily by placing the thumb on the coloured dot and gently pressing downwards as shown.

Dosage :
Arrhythmias :
By intravenous injection, dose up to 5 mg at rate 1 - 2 mg/minute, repeated after 5 minutes if necessary, total dose 10 - 15 mg. Note : Excessive bradycardia can be countered with intravenous injection of atropine sulphate 0.6 - 2.4 mg in divided doses of 600 micrograms.

In surgery :
By slow intravenous injection, dose of 2 - 4 mg at induction or to control arrhythmias developing during anaesthesia; 2 mg doses may be repeated to a maximum of 10 mg.

Early intervention within 12 hours of infarction :
By intravenous injection, dose of 5 mg every 2 minutes to a maximum of 15 mg, followed after 15 minutes by 50 mg by mouth every 6 hours for 48 hours; maintenance 200 mg daily in divided doses.

Hepatic impairment :
Reduce dose in severe impairment.

METOPROLOL  TARTRATE  INJECTION  USP as with other beta blockers, should not be used in patients with any of the following :

  • Hypotension.
  • AV block of second- or third-degree.
  • Decompensated cardiac failure (pulmonary oedema, hypoperfusion or hypotension).
  • Continuous or intermittent inotropic therapy acting through beta-receptor agonism.
  • Bradycardia (< 45 bpm).
  • Sick sinus syndrome (unless a permanent pacemaker is in place).
  • Cardiogenic shock.
  • Severe peripheral arterial circulatory disorder.
  • Untreated phaeochromocytoma.
  • Metabolic acidosis.

Known hypersensitivity to any component of METOPROLOL  TARTRATE  INJECTION  USP or other beta-blockers. METOPROLOL  TARTRATE  INJECTION  USP is also contra-indicated when suspected acute myocardial infarction is complicated by bradycardia (< 45 bpm), first-degree heart block or systolic blood pressure < 100 mmHg and/or severe heart failure.


Heart Failure :
Beta-blockers, like metoprolol, can cause depression of myocardial contractility and may precipitate heart failure and cardiogenic shock. If signs or symptoms of heart failure develop, treat the patient according to recommended guidelines. It may be necessary to lower the dose of metoprolol or to discontinue it.

Ischaemic Heart Disease :
Do not abruptly discontinue METOPROLOL  TARTRATE  INJECTION  USP therapy in patients with coronary artery disease. Severe exacerbation of angina, myocardial infarction and ventricular arrhythmias have been reported in patients with coronary artery disease following the abrupt discontinuation of therapy with beta-blockers. When discontinuing chronically administered METOPROLOL  TARTRATE  INJECTION  USP, particularly in patients with coronary artery disease, the dosage should be gradually reduced over a period of 1 to 2 weeks and the patient should be carefully monitored. If angina markedly worsens or acute coronary insufficiency develops, METOPROLOL  TARTRATE  INJECTION  USP administration should be reinstated promptly, at least temporarily, and other measures appropriate for the management of unstable angina should be taken. Patients should be warned against interruption or discontinuation of therapy without the physician’s advice. Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue METOPROLOL  TARTRATE  INJECTION  USP therapy abruptly even in patients treated only for hypertension.

Use During Major Surgery :
Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anaesthesia and surgical procedures.

Bradycardia :
Bradycardia, including sinus pause, heart block, and cardiac arrest have occurred with the use of metoprolol. Patients with first-degree atrioventricular block, sinus node dysfunction, or conduction disorders may be at increased risk. Monitor heart rate and rhythm in patients receiving metoprolol. If severe bradycardia develops, reduce or stop metoprolol.

Exacerbation of Bronchospastic Disease :
Patients with bronchospastic disease, should, in general, not receive beta-blockers, including metoprolol. Because of its relative beta1 selectivity, however, metoprolol may be used in patients with bronchospastic disease who do not respond to, or cannot tolerate, other antihypertensive treatment. Because beta1 selectivity is not absolute use the lowest possible dose of metoprolol and consider administering metoprolol in smaller doses three times daily, instead of larger doses two times daily, to avoid the higher plasma levels associated with the longer dosing interval. Bronchodilators, including beta2 agonists, should be readily available or administered concomitantly.

Diabetes and Hypoglycaemia :
Beta-blockers may mask tachycardia occurring with hypoglycaemia, but other manifestations such as dizziness and sweating may not be significantly affected.

Pheochromocytoma :

If metoprolol tartrate is used in the setting of pheochromocytoma, it should be given in combination with an alpha blocker, and only after the alpha blocker has been initiated. Administration of beta-blockers alone in the setting of pheochromocytoma has been associated with a paradoxical increase in blood pressure due to the attenuation of beta-mediated vasodilatation in skeletal muscle.

Thyrotoxicosis :
Metoprolol may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Avoid abrupt withdrawal of beta-blockade, which might precipitate a thyroid storm.

Risk of Anaphylactic Reactions :
While taking beta-blockers, patients with a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated challenge, either accidental, diagnostic, or therapeutic. Such patients may be unresponsive to the usual doses of epinephrine used to treat allergic reaction.



Pregnancy : Category C
Metoprolol - increased postimplantation loss and decrease neonatal survival in rats at doses up to 55.5 times the maximum daily human dose of 450 mg. No evidence of teratogenicity was seen in animal studies.

Nursing mothers : 
Metoprolol is distributed into breast milk. Although the risk appears to be small, breast-fed infants should be monitored for signs of beta-adrenergic blockade, especially bradycardia, hypotension, respiratory distress, and hypoglycaemia.

Paediatric Use : 
Safety and effectiveness in paediatric patients have not been established.

When driving vehicles or operating machines, it should be taken into account that occasionally dizziness or fatigue may occur.

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 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.

General Anaesthetics : 
Some inhalation anaesthetics may enhance the cardiodepressant effect of beta blockers.

CYP2D6 Inhibitors : 
Potent inhibitors of the CYP2D6 enzyme may increase the plasma concentration of metoprolol which would mimic the pharmacokinetics of CYP2D6 poor metabolizer. 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. 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 concurrently, and clonidine treatment is to be discontinued, stop metoprolol 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.

Cardiovascular : 
Hypotension; oedema; flushing; bradycardia. 

Central Nervous System : 
Headache; fatigue; dizziness; depression; lethargy; drowsiness; forgetfulness; sleepiness; vertigo; paresthesias. 

Dermatologic : 
Rash; facial erythema; alopecia; urticaria; pruritus. 

Eye, Ear, Nose, and Throat : 
Dry eyes; visual disturbances. 

Gastrointestinal : 
Nausea; vomiting; diarrhoea.

Genitourinary : 
Impotence; urinary retention; difficulty with urination.

Respiratory : 
Bronchospasm; dyspnoea; wheezing. 

Other : 
Increased hypoglycaemic response to insulin; may mask hypoglycaemic signs; muscle cramps; asthenia; systemic lupus erythematosus.

Advise patients :

  • To avoid operating automobiles and machinery or engaging in other tasks requiring alertness until the patient’s response to therapy with metoprolol has been determined. 
  • To contact the physician if any difficulty in breathing occurs.
  • To inform the physician or dentist before any type of surgery that he or she is taking metoprolol.

Acute Toxicity :
Several cases of overdosage have been reported, some leading to death. Oral LD50’s (mg/kg) : mice, 1158 to 2460; rats, 3090 to 4670.

Signs and Symptoms :
Potential signs and symptoms associated with overdosage with metoprolol are bradycardia, hypotension, bronchospasm, myocardial infarction, cardiac failure and death.

There is no specific antidote. In general, patients with acute or recent myocardial infarction may be more haemodynamically unstable than other patients and should be treated accordingly. On the basis of the pharmacologic actions of metoprolol, the following general measures should be employed : 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. 

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Store below 30°C (86°F), protected from light. 
Do not refrigerate.

24 months from the date of manufacture.

METOPROLOL  TARTRATE  INJECTION  USP is supplied as 5 mg of Metoprolol Tartrate USP in 5 ml aqueous solution. 
5 Ampoules of 5 ml per Box.


Disclaimer : For the use of a Registered Medical Practitioner or a Hospital or a Institution only. Also it is not intended to be used by healthcare professionals or patients for the purpose of prescribing or administering these products. Questions regarding the complete and current content of product labeling / specification / presentation should be directed to SGPharma.

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