Betaloc

Betaloc

metoprolol

Manufacturer:

AstraZeneca

Distributor:

Zuellig
/
Four Star
Full Prescribing Info
Contents
Metoprolol tartrate.
Description
Each tablet also contains lactose, magnesium stearate, microcrystalline cellulose, polyvinylpyrrolidone, silicon dioxide and sodium starch glycolate as excipients.
Action
Metoprolol is a β1-selective β-blocker ie, it blocks β1-receptors at doses much lower than those needed to block β2-receptors.
Metoprolol has an insignificant membrane-stabilising effect and does not display partial agonistic activity.
Metoprolol reduces or inhibits the agonistic effect on the heart of catecholamines (which are released during physical and mental stress). This means that the usual increase in heart rate, cardiac output, cardiac contractility and blood pressure, produced by the acute increase in catecholamines, is reduced by metoprolol. During high endogen adrenaline levels metoprolol interferes much less with blood pressure control than non-selective β-blockers.
When mandatory, Betaloc, in combination with a β2-agonist, may be given to patients with symptoms of obstructive pulmonary disease. When given together with a β2-agonist, Betaloc in therapeutic doses interferes less than non-selective β-blockers with the β2-mediated bronchodilation caused by the β2-agonist.
Metoprolol interferes less with insulin release and carbohydrate metabolism than do non-selective β-blockers.
Short-term studies have shown that metoprolol may cause a slight increase in triglycerides and a decrease in free fatty acids in the blood. In some cases, a small decrease in the high-density lipoproteins (HDL) fraction has been observed, although to a lesser extent than that following non-selective β-blockers. However, a significant reduction in total serum cholesterol levels has been demonstrated after metoprolol treatment in 1 study conducted over several years.
Quality of life is maintained uncompromised or improved during treatment with Betaloc.
An improvement in quality of life has been observed after metoprolol treatment in patients after myocardial infarction.
Pharmacokinetics: Absorption and Distribution: Betaloc is completely absorbed after oral administration. Within the therapeutic dosage range, the plasma concentrations rise linearly in relation to the size of the dose. Peak plasma concentrations are attained after approximately 1.5-2 hrs. Although the plasma profiles exhibit wide intersubject variability, they show good reproducibility within each individual. Administration of metoprolol in durules results in a successive release of active substance which means that the peak plasma levels are reduced. Compared to ordinary tablets the absorption phase is prolonged and the duration of effect extended. These factors may lead to more convenient dosage and an improved degree of β1-selectivity.
Owing to an extensive first-pass effect, the systemic bioavailability of metoprolol from a single oral dose is approximately 50%. Upon repeated administration, the systemically available portion of the dose increases to approximately 70%. Ingestion together with food may raise the systemic availability of an oral dose by approximately 30-40%. The plasma protein-binding of metoprolol is low, approximately 5-10%.
Metabolism and Elimination: Metoprolol undergoes oxidative metabolism in the liver. Three main metabolites have been identified, though none of them have a β-blocking effect of clinical importance.
As a rule, over 95% of an oral dose can be recovered in the urine. About 5% of the given dose is excreted in the urine in unchanged form, this figure rising up to 30% in isolated cases. The elimination half-life of metoprolol in plasma averages 3.5 hrs (extremes: 1 and 9 hrs). The total clearance rate is approximately 1 L/min.
Elderly show no significant changes in the pharmacokinetics of metoprolol as compared with young persons. The systemic bioavailability and elimination of metoprolol is unchanged in patients with a glomerulus filtration rate (GFR) of <5 mL/min. This accumulation of metabolites, however, does not increase the β-blockade.
Due to its low protein-binding, the pharmacokinetics of metoprolol is little affected by decreased liver function. However, in patients with severe liver cirrhosis and a portacava shunt, the bioavailability of metoprolol may increase and the total clearance may be reduced. Patients with a portacaval anastomosis had a total clearance of approximately 0.3 L/min and area under the plasma concentration-time curve (AUC) values up to 6 times higher than in healthy subjects.
Toxicology: Preclinical Safety Data: There is no toxicity data that would indicate that metoprolol tartrate is unsafe for use in the indications given. Signs in rats and dogs indicate that metoprolol can exert a cadiopressive action at high plasma levels.
Indications/Uses
Hypertension: To reduce blood pressure and to reduce the risk of cardiovascular and coronary mortality (including sudden death), and morbidity.
Angina pectoris and prophylaxis of migraine.
Disturbances of cardiac rhythm, including especially supraventricular tachycardia. Maintenance treatment after myocardial infarction. Functional heart disorders with palpitations. Hyperthyroidism.
Dosage/Direction for Use
The tablets should be taken on an empty stomach.
Hypertension: Recommended Dosage: 100-200 mg daily given as a single dose in the morning or in divided doses (morning and evening) or durule 200 mg given once daily. If needed, the dose may be increased or other antihypertensive agents added.
Long-term antihypertensive treatment with Betaloc in daily doses of 100-200 mg has been shown to reduce total mortality, including sudden cardiovascular death, stroke and coronary events in hypertensive patients.
Angina Pectoris: Recommended Dosage: 100-200 mg daily given in divided doses (morning and evening). If needed, the dose may be increased further or other antianginal agents added.
Cardiac Arrhythmias: Recommended Dosage: 100-200 mg daily given in divided doses (morning and evening). If needed, the dose may be increased further or other antiarrhythmic agents added.
Maintenance Treatment After Myocardial Infarction: Long-term oral treatment with Betaloc metoprolol in doses of 200 mg daily, given in divided doses (morning and evening) or as a durule 200 mg once daily has been shown to reduce the risk of death (including sudden death), and to reduce the risk of reinfarction (also in patients with diabetes mellitus).
Functional Heart Disorders with Palpitations: Recommended Dosage: 100 mg once daily, given as a single dose in the morning.
Migraine Prophylaxis: Recommended Dosage: 100-200 mg daily, given in divided doses (morning or evening) or durule 200 mg given once daily.
Hyperthyroidism: Recommended Dosage: 150-200 mg/day in 3-4 divided doses.
Impaired Renal Function: Dose adjustment is not needed in patients with impaired renal function.
Impaired Hepatic Function: Dose adjustment is normally not needed in patients suffering from liver cirrhosis because metoprolol has a low protein-binding (5-10%). When there are signs of serious impairment of liver function (eg, shunt-operated patients) a dose reduction should be considered.
Elderly: Dosage adjustment is not needed in the elderly.
Children: There is limited experience with Betaloc treatment in children.
Overdosage
Symptoms: Overdosage of Betaloc may lead to severe hypotension, sinus bradycardia, atrioventricular block, heart failure, cardiogenic shock, cardiac arrest, bronchospasm, impairment of consciousness/coma, nausea, vomiting, cyanosis, hypoglycaemia, and occasionally, hyperkalaemia.
Concomitant ingestion of alcohol, antihypertensives, quinidine or barbiturates may aggravate the patient's condition.
The first manifestations of overdosage may be observed 20 min to 2 hrs after the drug's ingestion.
Treatment: Activated charcoal, if necessary gastric lavage. In the presence of severe hypotension, bradycardia and impending heart failure, administer a β1-agonist (eg, prenalterol) IV at 2- to 5-min intervals or as a continuous infusion until the desired effect is achieved. Where a selective β1-agonist is not available, dopamine may be used; or atropine sulfate IV may be used in order to block the vagus nerve.
If a satisfactory effect is not achieved, other sympathomimetic agents eg, dobutamine may be used or adrenaline may be given. Glucagon in a dose of 1-10 mg can also be administered. Pacemaker may be necessary. To combat bronchospasm, a β2-agonist can be given IV.
Metoprolol cannot be effectively removed by haemodialysis.
Observe that the dosages of drugs (antidotes) needed to treat overdose of β-blockade are much higher than recommended therapeutic dosages. This is because β-receptors are occupied by the β-blocker.
Contraindications
Atrioventricular block of 2nd or 3rd degree, patients with unstable decompensated cardiac heart failure (pulmonary oedema, hypoperfusion or hypotension), and patients with continuous or intermittent inotropic therapy acting through β-receptor agonism; marked clinically relevant sinus bradycardia, sick-sinus syndrome, cardiogenic shock, severe peripheral arterial circulatory disorder.
Betaloc should not be given to patients with suspected acute myocardial infarction as long as the heart rate is <45 bpm, the P-Q interval is >0.24 sec or the systolic blood pressure is <100 mmHg.
Patients who have shown hypersensitivity to any component of Betaloc or to other β-blockers.
Metabolic acidosis and untreated phaeochromocytoma.
Special Precautions
IV administration of calcium antagonists of the verapamil-type should not be given to patients treated with β-blockers.
Generally when treating patients with asthma, concomitant therapy with a β2-agonist (tablet and/or aerosol) should be administered. The dosage of β2-agonists may require adjustment (increase) when treatment with Betaloc is started.
During treatment with Betaloc, the risk of their interfering with carbohydrate metabolism or masking hypoglycaemia is less than with nonselective β-blockers.
Patients suffering from heart failure should have their decompensation treated both before and during treatment with metoprolol.
Very rarely, a preexisting AV conduction disorder of moderate degree may become aggravated (possibly leading to AV block).
If the patient develops increasing bradycardia, Betaloc should be given in lower doses or gradually withdrawn.
Betaloc may aggravate the symptoms of peripheral arterial circulatory disorders, mainly due to its blood pressure-lowering effect.
Where Betaloc is prescribed for a patient known to be suffering from a phaeochromocytoma, an α-blocker should be given concomitantly.
Prior to surgery, the anaesthetist should be informed that the patient is receiving a Betaloc. It is not recommended to stop β-blocker treatment in patients undergoing surgery. Acute initiation of high-dose metoprolol to patients undergoing noncardiac surgery should be avoided, since it has been associated with bradycardia, hypotension and stroke including fatal outcome in patients with cardiovascular risk factors.
Abrupt interruption of the medication is to be avoided. If treatment has to be withdrawn it should, when possible, be done gradually. Many patients can be withdrawn over a 14-day period. This can be done by cutting the daily dose in sequential steps, reaching a final dose of 25 mg once a day (half a 50 mg tablet). During this period, especially patients with known ischemic heart disease should be kept under close surveillance. The risk of coronary events, including sudden death, may increase during withdrawal of β-blockade.
In patients taking β-blockers, anaphylactic shock assumes a more severe form.
Effects on the Ability to Drive or Operate Machinery: Patients should know how they react to Betaloc before they drive or use machines because occasionally, dizziness or fatigue may occur.
Use in pregnancy & lactation: As with most drugs, Betaloc should not be given during pregnancy and lactation unless its use is considered essential. As with all antihypertensive agents, β-blockers may cause side effects eg, bradycardia, in the fetus and in the newborn and breastfed infant.
The amount of metoprolol ingested via breast milk, however, seems to be negligible as regards β-blocking effect in the infant if the mother is treated with metoprolol in doses within the normal therapeutic range.
Use In Pregnancy & Lactation
Use in pregnancy & lactation: As with most drugs, Betaloc should not be given during pregnancy and lactation unless its use is considered essential. As with all antihypertensive agents, β-blockers may cause side effects eg, bradycardia, in the fetus and in the newborn and breastfed infant.
The amount of metoprolol ingested via breast milk, however, seems to be negligible as regards β-blocking effect in the infant if the mother is treated with metoprolol in doses within the normal therapeutic range.
Adverse Reactions
Betaloc is well tolerated and adverse reactions have generally been mild and reversible. The following events have been reported as adverse events in clinical trials or reported from routine use. In many cases, a relationship to treatment with Betaloc has not been established. The following definitions of frequencies are used: Very common (≥10%), common (1-9.9%), uncommon (0.1-0.9%), rare (0.01-0.09%) and very rare (<0.01%).
Cardiovascular System: Common: Bradycardia, postural disorders (very rarely with syncope), cold hands and feet, palpitations.
Uncommon: Transient deterioration of heart failure symptoms, cardiogenic shock in patients with acute myocardial infarction, AV-block I, oedema, precordial pain.
Rare: Disturbances of cardiac conduction, cardiac arrhythmias.
Very Rare: Gangrene in patients with preexisting severe peripheral circulatory disorders.
Central Nervous System: Very Common: Fatigue.
Common: Dizziness, headache.
Uncommon: Paraesthesiae, muscle cramps.
Gastrointestinal: Common: Nausea, abdominal pain, diarrhoea, constipation.
Uncommon: Vomiting.
Rare: Dry mouth.
Haematologic: Very Rare: Thrombocytopenia.
Hepatic: Rare: Liver function test abnormalities. Very Rare: Hepatitis.
Metabolism: Uncommon: Weight gain.
Psychiatric: Uncommon: Depression, impaired concentration, somnolence or insomnia, nightmares.
Rare: Nervousness, anxiety, impotence/sexual dysfunction.
Very Rare: Amnesia/memory impairment, confusion, hallucinations.
Respiratory: Common: Dyspnoea on exertion.
Uncommon: Bronchospasm.
Rare: Rhinitis.
Skin: Uncommon: Rash (in the form of urticaria, psoriasiform and dystrophic skin lesions), increased sweating.
Rare: Loss of hair.
Very Rare: Photosensitivity reactions, aggravated psoriasis.
Drug Interactions
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. Plasma levels of metoprolol may be raised by co-administration of compounds metabolised by CYP2D6, eg, antiarrhythmics, antihistamines, histamine-2-receptor antagonists, antidepressants, antipsychotics, and COX-2 inhibitors. The plasma concentration of metoprolol is lowered by rifampicin and may be raised by alcohol and hydralazine.
Patients receiving concomitant treatment with sympathetic ganglion-blocking agents, other β-blockers (ie, eye drops) or monoamine oxidase (MAO) inhibitors should be kept under close surveillance.
If concomitant treatment with clonidine is to be discontinued, the β-blocker medication should be withdrawn several days before clonidine.
A watch should be kept for possible negative inotropic and chronotropic effects when metoprolol is given together with calcium antagonists of the verapamil and diltiazem type and/or antiarrhythmic agents. In patients treated with β-blockers, IV 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 β-blockers, may increase atrioventricular conduction time and may induce bradycardia.
In patients receiving β-blocker therapy, inhalation anaesthetics enhance the cardiodepressant effect.
Concomitant treatment with indomethacin or other prostaglandin synthetase-inhibiting drugs may decrease the antihypertensive effect of β-blockers.
Under certain conditions, when adrenaline is administered to patients treated with β-blockers, cardioselective β-blockers interfere much less with blood pressure control than nonselective β-blockers.
The dosages of oral antidiabetics may have to be readjusted in patients receiving β-blockers.
MIMS Class
ATC Classification
C07AB02 - metoprolol ; Belongs to the class of selective beta-blocking agents. Used in the treatment of cardiovascular diseases.
Presentation/Packing
Tab 50 mg (white to off-white, circular, scored and marked
Click on icon to see table/diagram/image
on one side) x 100's. 100 mg (white to off-white, circular, scored and marked
Click on icon to see table/diagram/image
on one side) x 100's.
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