METOPROLOL TARTRATE

Posology The dose must always be adjusted to the individual requirements of the patient but should not exceed 400 mg/day.

The following are guidelines:

Adults: Hypertension: Initially, 100 mg daily, increased by 100 mg daily at weekly intervals to 200 mg daily if needed, in single or divided (twice daily) doses. Over the dosage range most patients may be expected to respond rapidly and satisfactorily.

A further reduction in blood pressure may be achieved if Metoprolol tablets are used in conjunction with an antihypertensive diuretic or other hypotensive agent. Metoprolol tablets may be administered with benefit both to previously untreated patients with hypertension and to those in whom the response to previous therapy is inadequate.

In the latter type of patient the previous therapy may be continued and Metoprolol tablets added into the regime with adjustment of the previous therapy if necessary. Angina Pectoris: 50-100 mg two or three times daily. In general a significant improvement in exercise tolerance and reduction of anginal attacks may be expected with a dose of 50-100 mg twice daily.

Cardiac Arrhythmias: 50 mg two or three times daily is usually sufficient. If necessary the dose can be increased up to 300 mg daily in divided doses. Migraine Prophylaxis: 100-200 mg daily in divided doses (morning and evening). Hyperthyroidism: 50 mg four times daily.

The dose should be progressively reduced as the euthyroid state is slowly achieved.

Myocardial Infarction:

Early intervention: 50 mg every six hours for 48 hours, commencing 15 minutes after the last intravenous dose of metoprolol, and preferably within 12 hours of the onset of chest pain. Maintenance: 100 mg twice daily as a maintenance dose.

The treatment should be continued for at least 3 months. Patients who do not tolerate the full intravenous dose of metoprolol should be given half the suggested oral dose.

Paediatric population:

Not recommended.

Older people:

The optimum dose should be individually determined according to clinical response. There is no evidence to suggest that dosage requirements are different in otherwise healthy older patients. However, caution is indicated in older patients as an excessively pronounced decrease in blood pressure or pulse rate may cause the blood supply to vital organs to fall to inadequate levels.

Hepatic Disease:

In patients with significant hepatic dysfunction dosage reduction may be advised. Method of administration Metoprolol tablets should be administered orally and swallowed unchewed.

Frequency estimates: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data). g. g. hypoacusis or deafness) Cardiac disorders Common bradycardia Rare heart failure, cardiac arrhythmias, palpitation Very rare disturbances of cardiac conduction, precordial pain Vascular disorders Common orthostatic hypotension (occasionally with syncope) Rare oedema, Raynaud’s phenomenon Not known hypotension Very rare gangrene in patients with pre-existing severe peripheral circulatory disorders Respiratory, thoracic and mediastinal disorders Common exertional dyspnoea Rare bronchospasm (which may occur in patients without a history of obstructive lung disease) Very rare rhinitis Gastrointestinal disorders Common nausea and vomiting, abdominal pain Rare diarrhoea or constipation Very rare dryness of the mouth Not known retroperitoneal fibrosis (relationship to metoprolol has not definitely been established) Hepatobiliary disorders Not known hepatitis Skin and subcutaneous tissue disorders Rare skin rash (in the form of urticaria, psoriasiform and dystrophic skin lesions) Very rare photosensitivity, increased sweating, loss of hair, worsening of psoriasis Musculoskeletal and connective tissue disorders Rare muscle cramps Very rare arthritis Reproductive system and breast disorders Very rare disturbances of libido and potency Not known Peyronie’s disease (relationship to metoprolol has not been definitely established) General disorders and administration site conditions Common fatigue Investigations Very rare weight gain, liver function test abnormalities Not known positive anti-nuclear antibodies Post Marketing Experience The following adverse reactions have been reported during post-approval use of metoprolol: 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. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard.

Sudden withdrawal of beta-adrenoceptor blocking drugs should be avoided, especially in patients with ischaemic heart disease as it may result in anginal attacks of increased frequency or severity. Therefore, withdrawal of metoprolol should be gradual over 10 days, reducing the dose to 25 mg daily for the last 6 days.

During its withdrawal, the patient should be kept under close surveillance and replacement therapy should be initiated where required. Beta-blockers may increase the number and duration of angina attacks in patients with Prinzmetal’s angina (variant angina pectoris).

However, relatively selective beta1-receptor blockers, such as metoprolol, can be used in such patients, but only with the utmost care. Particular care is required with patients whose cardiac reserve is poor. Beta-adrenoceptor blocking drugs should be avoided in overt heart failure, although they may be used when cardiac failure has been controlled.

Digitalisation and/or diuretic therapy should be considered in patients with a history of heart failure. Cardiac failure due to thyrotoxicosis may respond to metoprolol alone, but if other adverse factors are also present it is important to control signs of failure with cardiac glycosides and diuretics.

3). In patients with a phaeochromocytoma, an alpha-blocker should be given concomitantly. A reduction in heart rate is a pharmacological effect of metoprolol. In rare cases where symptoms may be attributable to the slow heart rate (less than 50 to 55 beats/min), the dose should be reduced or gradually withdrawn.

Metoprolol modifies the tachycardia of hypoglycaemia by inhibition of sympathetic nerve functions and it may prolong the hypoglycaemic response to insulin. Patients should be warned accordingly. Care should be exercised during concomitant use of metoprolol and hypoglycaemic therapy in patients with diabetes mellitus.

In labile and insulin-dependent diabetes it may be necessary to adjust the hypoglycaemic therapy. Beta-blockers could further increase the risk of severe hypoglycaemia when used concurrently with sulfonylureas. 5). Beta-blockers should be used with great caution in patients with peripheral circulatory disorders (Raynaud’s disease/syndrome, intermittent claudication), and bradycardia, as they may aggravate such disorders.

Beta-blockers may increase both the sensitivity towards allergens and the seriousness of anaphylactic reactions which may be resistant to normal doses of adrenaline. Whenever possible, beta-blockers, including metoprolol, should be avoided for patients who are at increased risk of anaphylaxis.

While cardioselective beta-blockers such as metoprolol may have less effect on pulmonary function than non-selective ones, they should be avoided in patients with reversible obstructive airways disease, a history of asthma and/or bronchospasm unless absolutely necessary.

When administration of metoprolol is required, the use of a beta2-bronchodilator such as terbutaline may be advisable or current therapy may require adjustment in some cases. When beta-blockers are used in patients with a history of bronchial asthma, the possibility of bronchospasm must be considered.

The label will state “Do not take this medicine if you have a history of wheezing or asthma”. Care is required when transferring patients from clonidine to a beta-adrenoceptor blocking drug. If the two drugs are given concurrently, clonidine should not be discontinued until several days after the withdrawal of the beta-adrenoceptor blocking drug.

Beta-adrenoceptor blocking drugs should be used with caution in combination with verapamil where ventricular function is impaired. The combination should not be given to patients with conduction abnormalities, nor should either drug be administered intravenously within 48 hours of discontinuing the other.

5). Care is required when administering anaesthetic agents to patients receiving metoprolol. The anaesthetist should always be informed of the use of a beta-adrenoceptor blocking drug. The risks and benefits of continued beta-blocking therapy in the peri-operative period should be carefully evaluated.

If a beta-blocker is withdrawn prior to surgery it should be discontinued for at least 24 hours. Continuation of beta-blockade reduces the risk of arrhythmias during induction and intubation. However, the risk of hypertension may be increased.

If treatment is continued, caution should be observed with the use of certain anaesthetic drugs. In a patient under beta-blockade, the anaesthetic selected should be one exhibiting as little negative inotropic activity as possible (halothane/nitrous oxide).

The patient may be protected against vagal reactions by intravenous administration of atropine. Patients with anamnestically known psoriasis should take beta-blockers only after careful consideration. In patients with significant hepatic dysfunction it may be necessary to adjust the dosage because metoprolol undergoes biotransformation in the liver.

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.

The full oculomucocutaneous syndrome, as described elsewhere […]

g. in some diabetics). Metoprolol is also contraindicated when myocardial infarction is complicated by significant bradycardia, first degree heart block, systolic hypotension (less than 100 mmHg) and/or severe heart failure.