Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use
Abrupt cessation of therapy with a beta-blocker should be avoided especially in patients with ischaemic heart disease. When possible, metoprolol should be withdrawn gradually over a period of 10 days, the doses diminishing to 25mg for the last 6 days. If necessary, at the same time, initiating replacement therapy, to prevent exacerbation of angina pectoris. In addition, hypertension and arrhythmias may develop. When it has been decided to interrupt a betablockade in preparation for surgery, therapy should be discontinued for at least 24 hours. Continuation of betablockade reduces the risk of arrhythmias during induction and intubation, however the risk of hypertension may be increased as well. If treatment is continued, caution should be observed with the use of certain anaesthetic drugs.
The patient may be protected against vagal reactions by intravenous administration of atropine. During its withdrawal the patient should be kept under close surveillance.

Although cardioselective beta-blockers may have less effect on lung function than non selective beta-blockers these should be avoided in patients with reversible obstructive airways disease unless there are compelling clinical reasons for their use. Although metoprolol has proved safe in a large number of asthmatic patients, it is advisable to exercise care in the treatment of patients with chronic obstructive pulmonary disease. Therapy with a beta2- stimulant may become necessary or current therapy require adjustment.
Therefore, non-selective beta-blockers should not be used for these patients, and beta-1 selective blockers only with the utmost care.

Discontinuation of the drug should be considered if any such reaction is not otherwise explicable. Cessation of therapy with a beta-blocker should be gradual.

Neobloc tablets may not be administered to patients with untreated congestive heart failure. The congestive heart failure needs to be brought under control first of all. If concomitant digoxin treatment is taking place, it must be borne in mind that both medicinal products slow AV conduction and that there is therefore a risk of AV dissociation. In addition, mild cardiovascular complications may occur, manifesting as dizziness, bradycardia, and a tendency to collapse.

When a beta blocker is being taken, a serious, sometimes even life-threatening deterioration in cardiac function can occur, in particular in patients in whom the action of the heart is dependent on the presence of sympathetic system support.
This is due less to an excessive beta-blocking effect and more to the fact that patients with marginal heart function tolerate poorly a reduction in sympathetic nervous system activity, even where this reduction is slight. This causes contractility to become weaker and the heart rate to reduce and slows
down AV conduction. The consequence of this can be pulmonary oedema, AV block, and shock. Occasionally, an existing AV conduction disturbance can deteriorate, which can lead to AV block.

In patients with a phaeochromocytoma, an alpha blocker should be given concomitantly.
Before a patient undergoes an operation, the anaesthetist must be informed that metoprolol is being taken. Acute initiation of high-dose metoprolol to patients undergoing non-cardiac surgery should be avoided, since it has been associated with bradycardia, hypotension and stroke including fatal outcome in patients with cardiovascular risk factors.

Beta-blockers mask some of the clinical signs of thyrotoxicosis. Therefore, Metoprolol should be administered with caution to patients having, or suspected of developing, thyrotoxicosis, and both thyroid and cardiac function should be monitored closely.

Simultaneous administration of adrenaline (epinephrine), noradrenaline (norepinephrine) and β blockers may lead to an increase of blood pressure and bradycardia.

Metoprolol may induce or aggravate bradycardia, symptoms of peripheral arterial circulatory disorders and anaphylactic shock. If the pulse rate decreases to less than 50 to 55 beats/min at rest and the patient experiences symptoms related to bradycardia, the dosage should be reduced.
Metoprolol 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 may reduce the effect of diabetes treatment and mask the symptoms of hypoglycaemia. The risk of a carbohydrate metabolism disorder or masking of the symptoms of hypoglycaemia is lower when using metoprolol prolonged-release tablets than when using regular tablet forms for beta1 selective beta blockers and significantly lower than when using non- selective beta blockers. In labile and insulin-dependent diabetes, it may be necessary to adjust the hypoglycaemic therapy.

In case of unstable or insulin-dependent diabetes mellitus, it may be necessary to adjust the hypoglycaemic treatment (because of the likelihood of severe hypoglycaemic conditions).

In patients with significant hepatic dysfunction it may be necessary to adjust the dosage because metoprolol undergoes biotransformation in the liver.
Patients with hepatic or renal insufficiency may need a lower dosage, and metoprolol is contraindicated in patients with hepatic or renal disease/failure (see section 4.3). The elderly should be treated with caution, starting with a lower dosage but tolerance is usually good in the elderly. It may be necessary to use a lower strength formulation in elderly patients and patients with hepatic or renal impairment and an alternative product should be prescribed.
Patients with anamnestically known psoriasis should take beta-blockers only after careful consideration as the medicine may cause aggravation of psoriasis.
Beta-blockers may increase both the sensitivity towards allergens and the seriousness of anaphylactic reactions. Adrenaline (epinephrine) treatment does not always give the desired therapeutic effect in individuals receiving beta blockers (see also section 4.5).

Beta-blockers may unmask myasthenia gravis.
In the presence of liver cirrhosis, the bioavailability of metoprolol may be increased, and dosage should be adjusted accordingly.

Important information regarding the ingredients in this medicine
Lactose: This medicinal product contains lactose (35 mg per tablet). Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Sodium: This medicine contains less than 1mmol sodium (20 mg) per tablet, that is to say essentially (sodium-free).

Dry eyes either alone or, occasionally, with skin rashes has occurred. In most cases the symptoms cleared when metoprolol treatment was withdrawn. Patients should be observed carefully for potential ocular effects. If such effects occur, discontinuation of metoprolol should be considered.

Effects on Driving

4.7   Effects on ability to drive and use machines
As with all beta-blockers, metoprolol may affect patients' ability to drive and operate machinery because of dizziness and fatigue. Patients should be warned accordingly. These effects may possibly be enhanced in case of concomitant ingestion of alcohol or after changing to another medicinal product.