| Composition |
| Each ampoule 5 ml contains: 5 mg Metoprolol Tartrate. |
| Excipients |
| Sodium chloride, Water for Injection |
| Pharmacodynamics |
Mechanism of action:
Metoprolol is a competitive beta-adrenoceptor antagonist. It acts preferentially to inhibit beta-adrenoceptors (conferring some cardioselectivity), is devoid of intrinsic sympathomimetic activity (partial agonist activity) and possesses beta-adrenoceptor blocking activity comparable in potency with propranolol.
Pharmacodynamic effects:
A negative chronotropic effect on the heart is a consistent feature of Metoprolol administration. Thus, cardiac output and systolic blood pressure rapidly decrease following acute administration. |
| Indications |
Control of tachyarrhythmias, especially supraventricular tachyarrhythmias.
Early intervention with Metobloc in acute myocardial infarction reduces infarct size and the incidence of ventricular fibrillation. Pain relief may also decrease the need for opiate analgesics.
Metobloc has been shown to reduce mortality when administered to patients with acute myocardial infarction. |
| Dosage |
The dose must always be adjusted to the individual requirements of the patient. The following are guidelines:
Cardiac arrhythmias:
Initially up to 5 mg injected intravenously at a rate of 1-2 mg per minute. The injection can be repeated at 5 minute intervals until a satisfactory response has been obtained. A total dose of 10-15 mg generally proves sufficient.
Because of the risk of a pronounced drop of blood pressure, the I.V. administration of Metoprolol to patients with a systolic blood pressure below 100 mmHg should only be given with special care.
During Anaesthesia:
2-4 mg injected slowly I.V. at induction is usually sufficient to prevent the development of arrhythmias during anaesthesia. The same dosage can also be used to control arrhythmias developing during anaesthesia. Further injections of 2 mg may be given as required to a maximum overall dose of 10 mg.
Myocardial infarction:
Metoprolol should be initiated in a coronary care or similar unit when the patient’s haemodynamic condition has stabilised.
Therapy should commence with 5 mg I.V. every 2 minutes to a maximum of 15 mg total as determined by blood pressure and heart rate. The second or third dose should not be given if the systolic blood pressure is <90 mmHg, the heart rate is <40 beats/min and the P-Q time is >0.26 seconds, or if there is any aggravation of dyspnoea or cold sweating. Oral therapy should commence 15 minutes after the last injection with 50 mg every 6 hours for 48 hours. Patients who fail to tolerate the full intravenous dose should be given half the suggested oral dose.
Renal impairment:
Dose adjustment is generally not needed in patients with impaired renal function.
Hepatic Impairment:
Dose adjustment is normally not needed in patients suffering from liver cirrhosis because Metoprolol has a low protein binding (5 – 10 %). However, in patients with severe hepatic dysfunction a reduction in dosage may be necessary.
Elderly:
Several studies indicate that age related physiological changes have negligible effects on the pharmacokinetics of Metoprolol . Dose adjustment is not needed in the elderly, but careful dose titration is important in all patients.
Paediatric population:
The safety and efficacy of Metoprolol in children has not been established. |
| Contraindications |
Metoprolol, as with other beta blockers, should not be used in patients with any of the following:
- Hypersensitivity to the active substance, or to any of the excipients.
- Hypotension.
- AV block of second- or third-degree.
- Decompensated cardiac failure (pulmonary oedema, hypoperfusion or hypotension).
- Continuous or intermittent inotropic therapy acting through betareceptor 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.
Metoprolol is also contra-indicated when suspected acute myocardial infarction is complicated by bradycardia (<45 bpm), firstdegree heart block or systolic blood pressure <100 mmHg and/or severe heart failure. |
| Warnings and Precautions |
When treating patients with suspected or definite myocardial infarction the haemodynamic status of the patient should be carefully monitored after each of the three 5 mg intravenous doses. The second or third dose should not be given if the heart rate is <40 beats/min, the systolic blood pressure is <90 mmHg and the P-Q time is >0.26 sec, or if there is any aggravation of dyspnoea or cold sweating.
Metoprolol , as with other beta blockers:
- Should not be withdrawn abruptly during oral treatment. When possible, Metoprolol IV injection should be withdrawn gradually over a period of 10 – 14 days, in diminishing doses to 25 mg daily for the last 6 days. During its withdrawal patients should be kept under close surveillance, especially those with known ischaemic heart disease. The risk for coronary events, including sudden death, may increase during the withdrawal of betablockade.
- Must be reported to the anaesthetist prior to general anaesthesia.
It is not generally recommended to stop Metoprolol treatment in patients undergoing surgery. If withdrawal of Metoprolol is considered desirable, this should, if possible, be completed at least 48 hours before general anaesthesia. Routine initiation of high-dose Metoprolol to patients undergoing noncardiac surgery should be avoided, since it has been associated with bradycardia, hypotension ,stroke and increased mortality in patients with cardiovascular risk factors. However in some patients it may be desirable to employ a beta-blocker as premedication. In such cases an anaesthetic with little negative inotropic activity should be selected to minimise the risk of myocardial depression.
- Although contra-indicated in severe peripheral arterial circulatory disturbances, may also aggravate less severe peripheral arterial circulatory disorders.
- May be administered when heart failure has been controlled.
Digitalisation and/or diuretic therapy should also be considered for patients with a history of heart failure, or patients known to have a poor cardiac reserve. Metoprolol should be used with caution in patients where cardiac reserve is poor.
- May cause patients to develop increasing bradycardia, in such cases the Metoprolol dosage should be reduced or gradually withdrawn.
- Due to the negative effect on conduction time, should only be given with caution to patients with first-degree heart block.
- May increase the number and duration of angina attacks in patients with Prinzmetal’s angina, due to unopposed alphareceptor mediated coronary artery vasoconstriction. Metoprolol is a beta1-selective beta-blocker; consequently, its use may be considered although utmost caution must be exercised.
- May mask the early signs of acute hypoglycaemia, in particular tachycardia. During treatment with Metoprolol , the risk of interfering with carbohydrate metabolism or masking hypoglycaemia is less than with non-selective beta-blockers.
- May mask the symptoms of thyrotoxicosis.
- May increase both the sensitivity towards allergens and the seriousness of anaphylactic reactions.
Although cardioselective beta-blockers may have less effect on lung function than non-selective beta-blockers, as with all beta-blockers, these should be avoided in patients with reversible obstructive airways disease unless there are compelling clinical reasons for their use. When administration is necessary, these patients should be kept under close surveillance. The use of a beta2-bronchodilator (e.g. terbutaline) may be advisable in some patients. The dosage of the beta2-agonist may require an increase when treatment with Metoprolol is commenced.
Like all beta-blockers, careful consideration should be given to patients with psoriasis before Metoprolol is administered.
In patients with a phaeochromocytoma, an alpha-blocker should be given concomitantly.
In labile and insulin-dependent diabetes it may be necessary to adjust the hypoglycaemic therapy.
Intravenous administration of calcium antagonists of the verapamil type should not be given to patients treated with beta-blockers. |
| Drugs Interaction |
Metoprolol is a metabolic substrate for the Cytochrome P450 isoenzyme CYP2D6. Drugs that act as enzyme-inducing and enzyme-inhibiting substances may exert an influence on the plasma level of Metoprolol .
Enzyme inducing agents (e.g. rifampicin) may reduce plasma concentrations of METOPROLOL whereas enzyme inhibitors (e.g. cimetidine, alcohol and hydralazine) may increase plasma concentrations.
Patients receiving concomitant treatment with sympathetic ganglion blocking agents, other beta blockers (i.e. eye drops), or Mono Amine Oxidase (MAO) inhibitors should be kept under close surveillance.
If concomitant treatment with clonidine is to be discontinued, METOPROLOL should be withdrawn several days before clonidine.
Increased negative inotropic and chronotropic effects may occur when Metoprolol is given together with calcium antagonists of the verapamil and diltiazem type. In patients treated with beta-blockers intravenous administration of calcium antagonists of the verapamil-type should not be given.
Beta-blockers may enhance the negative inotropic and negative dromotropic effect of antiarrhythmic agents (of the quinidine type and amiodarone).
Digitalis glycosides, in association with beta-blockers, may increase atrioventricular conduction time and may induce bradycardia.
In patients receiving beta-blocker therapy, inhalation anaesthetics enhance the cardiodepressant effect.
Concomitant treatment with indometacin and other prostaglandin synthetase inhibiting drugs may reduce the antihypertensive effect of betablockers.
The administration of adrenaline (epinephrine) to patients undergoing betablockade can result in an increase in blood pressure and bradycardia although this is less likely to occur with beta1-selective drugs.
Metoprolol will antagonise the beta1-effects of sympathomimetic agents but should have little influence on the bronchodilator effects of beta2-agonists at normal therapeutic doses.
Metoprolol may impair the elimination of lidocaine.
As with other beta-blockers, concomitant therapy with dihydropyridines e.g. nifedipine, may increase the risk of hypotension, and cardiac failure may occur in patients with latent cardiac insufficiency.
The dosages of oral antidiabetic agents and also of insulin may have to be readjusted in patients receiving beta-blockers.
As beta-blockers may affect the peripheral circulation, care should be exercised when drugs with similar activity e.g. ergotamine are given concurrently.
The effects of Metoprolol and other drugs with an antihypertensive effect on blood pressure are usually additive. Care should be taken when combining with other antihypertensive drugs or drugs that might reduce blood pressure such as tricyclic antidepressants, barbiturates and phenothiazines. However, combinations of antihypertensive drugs may often be used with benefit to improve control of hypertension. |
| Pregnancy & lactations |
Metoprolol should not be used in pregnancy or nursing mothers unless the physician considers that the benefit outweighs the possible hazard to the fetus/infant.
Breast-feeding is not recommended. The amount of Metoprolol ingested via breast milk should not produce significant beta-blocking effects in the neonate if the mother is treated with normal therapeutic doses. |
| Overdosage |
Symptoms:
Symptoms of overdose may include hypotension, cardiac insufficiency, bradycardia and bradyarrhythmia, cardiac conduction disturbances and bronchospasm.
Management:
Care should be provided at a facility that can provide appropriate supporting measures, monitoring and supervision.
Atropine, adrenostimulating drugs or pacemaker to treat bradycardia and conduction disorders.
Hypotension, acute cardiac failure, and shock to be treated with suitable volume expansion, injection of glucagon (if necessary, followed by an intravenous infusion of glucagon), intravenous administration of adrenostimulating drugs such as dobutamine, with α1 receptor agonistic drugs added in presence of vasodilation. Intravenous use of Ca2+ can also be considered.
Bronchospasm can usually be reversed by bronchodilators. |
| Storage & Packaging |
Storage Conditions:
Store below 25⁰C, Protect from light
Packaging:
Metobloc: Carton box of 5 glass ampoules each contains 5 ml inside plastic tray with a leaflet.
Metobloc: Carton box of 50 glass ampoules of 5 ml with a leaflet, each 5 ampoulrs inside plastic tray. |
