Reasons for adding or updating:

• Change to section 4.2 - Posology and method of administration
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 30-Dec-2016

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 4.2- changes to sub-heading fro renal impairment, hepatic impairement and elderly to be aligned with QRD template.

Section 10- change to revision date

Reasons for adding or updating:

• Change to section 4.1 - Therapeutic indications
• Change to section 4.2 - Posology and method of administration
• Change to section 2 - Qualitative and quantitative composition
• Change to section 4.4 - Special warnings and precautions for use
• Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
• Change to section 4.6 - Fertility, pregnancy and lactation
• Change to section 4.7 - Effects on ability to drive and use machines
• Change to section 4.8 - Undesirable effects - how to report a side effect
• Change to section 5.1 - Pharmacodynamic properties
• Change to section 5.2 - Pharmacokinetic properties
• Change to section 6.2 - Incompatibilities
• Change to section 6.3 - Shelf life
• Change to section 6.6 - Special precautions for disposal and other handling
• Change to section 9 - Date of first authorisation/renewal of the authorisation
• Change to section 10 - Date of revision of the text
• Change to section 4.3 - Contraindications

Date of revision of text on the SPC: 02-Sep-2014

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



-Section 2 updated in line with QRD template

- Section 4.1 updated in line with QRD template

- Section 4.2 updated in line with QRD template

- Section 4.3 updated in line with QRD template

- Section 4.4 updated in line with QRD template

- Section 4.5 updated in line with QRD template

- Section 4.6 updated in line with QRD template, addition of following: ‘In general, beta-blockers reduce placental perfusion, which has been associated with intrauterine death, abortion and early labour. It is therefore suggested that appropriate maternofoetal monitoring be performed in pregnant women treated with Betaloc I.V. Injection’

- Section 4.7 updated in line with QRD template

-section 4.8 updated in line with QRD template

-secyion 5.1 updated in line with QRD template

-section 5.2 updated in line with QRD template

-section 6.2 updated in line with QRD template

-section 6.3 updated in line with QRD template

- section 6.6 updated in line with QRD template

-section 9 updated in line with QRD template
-section 10 updated revision date

Reasons for adding or updating:

• Change to section 4.3 - Contraindications
• Change to section 4.8 - Undesirable effects
• Change to section 4.8 - Undesirable effects - how to report a side effect
• Change to section 4.9 - Overdose
• Change to section 10 - Date of revision of the text

Date of revision of text on the SPC: 20-Dec-2013

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 4.3: Contradindications: addition of ‘unless a permanent pacemaker is in place’ text and editorial changes

Section 4.8: formatting changes and addition of adverse event reporting statement

Section 4.9: Amendment of text in overdose section

Section 10 – Update to "Date of Revision"

Reasons for adding or updating:

• Change to section 4.4 - Special warnings and precautions for Use
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 01-Sep-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 4.4

Changed text  - 2^nd bullet point

• must be reported to the anaesthetist prior to general anaesthesia. It is not generally recommended to stop Betaloc 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 non-cardiac 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.

Section 10

Revised date of text: 1st September 2010

Reasons for adding or updating:

• Change to section 4.2 - Posology and method of administration
• Change to section 4.9 - Overdose
• Change to section 5.1 - Pharmacodynamic Properties
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 17-Sep-2008

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 4.2

Myocardial infarction:
Early intervention. Intravenous Betaloc should be initiated in a coronary care or similar unit when the patient’s haemodynamic condition has stabilised.  To achieve optimal benefits from intravenous Betaloc, suitable patients should present within 12 hours of the onset of chest pain.  Such treatment should be initiated in a coronary care or similar unit immediately after the patients 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.

Section 4.9

The symptoms of overdose may include bradycardia, hypotension, acute cardiac insufficiency and bronchospasm.

General treatment should include:

Close supervision, treatment in an intensive care ward and the use of plasma or plasma substitutes to treat hypotension and shock.

Excessive bradycardia can be countered with atropine 1-2 mg intravenously and/or a cardiac pacemaker.  If necessary, this may be followed by a bolus dose of glucagon 10 mg intravenously.  If required, this may be repeated or followed by an intravenous infusion of glucagon 1-10 mg/hour depending on response.  If no response to glucagon occurs or if glucagon is unavailable, a beta adrenoceptor stimulant such as dobutamine 2.5 to 10 micrograms/kg/minute by intravenous infusion may be given. 

Dobutamine, because of its positive inotropic effect could also be used to treat hypotension and acute cardiac insufficiency. It is likely that these doses would be inadequate to reverse the cardiac effects of beta blockade if a large overdose has been taken.  The dose of dobutamine should therefore be increased if necessary to achieve the required response according to the clinical condition of the patient.

Administration of calcium ions may also be considered. Bronchospasm can usually be reversed by bronchodilators.Symptoms
Poisoning due to an overdose of Betaloc Injection 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, barbiturates or other drugs and combinations of drugs that might negatively affect the circulatory system and/or the central nervous system, may aggravate the patient’s condition.

Management
Treatment should include close monitoring of cardiovascular, respiratory and renal function, and blood glucose and electrolytes.  Cardiovascular complications should be treated symptomatically. In the presence of severe hypotension, bradycardia, and impending heart failure, administer a beta₁-agonist until the desired effect is achieved. Where a selective beta₁-agonist is not available, dopamine may be used; or atropine sulphate i.v. may be used in order to block the vagus nerve. If a satisfactory effect is not achieved, other sympathomimetic agents (e.g. noradrenaline [norepinephrine], metaraminol) or inotropic agents, (e.g. dobutamine) may be used. Temporary pacing may be required for AV block.  Glucagon can reverse the effects of excessive beta-blockade, given in a dose of 1-10 mg intravenously. 

Intravenous beta₂-stimulants e.g. terbutaline may be required to relieve bronchospasm.

It should be noted that the dosages of drugs (antidotes) needed to treat overdose of beta-blockade are much higher than normally recommended therapeutic dosages. This is because the beta receptors are occupied by the beta-blocker.

Betaloc Injection cannot be effectively removed by haemodialysis.

Section 5.1

Pharmacotherapeutic group: Beta blocking agents, selective
ATC code: C07AB02

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.

A negative chronotrophic effect on the heart is a consistent feature of metoprolol administration. Thus, cardiac output and systolic blood pressure rapidly decrease following acute administration.

The intention to treat trial COMMIT included 45,852 patients admitted to hospital within 24 hours of the onset of symptoms of suspected acute myocardial infarction with supporting ECG abnormalities (i.e. ST elevation, ST depression or left bundle-branch block). Patients were randomly allocated to metoprolol (up to 15 mg intravenous then 200 mg oral) or placebo and treated until discharge or up to 4 weeks in hospital. The two co-primary outcomes were: (1) composite of death, reinfarction or cardiac arrest; and (2) death from any cause during the scheduled treatment period. Neither of the co-primary outcomes was significantly reduced by metoprolol. However, metoprolol treatment was associated with fewer people having reinfarction and ventricular fibrillation but an increased rate of cardiogenic shock during the first day after admission. There was substantial net hazard in haemodynamically unstable patients. There was moderate net benefit in those who were stable, particularly after days 0-1.

Section 10
updated to 17th September 2008

Reasons for adding or updating:

• Change to section 4.8 - Undesirable Effects
• Change to section 10 date of revision of the text

Date of revision of text on the SPC: 01-Jan-2008

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 4.8

Under the heading of Cardiac disorders:

Additional text regarding cardiogenic shock

 

* Excess frequency of 0.4 % compared with placebo in a study of 46,000 patients with acute myocardial infarction where the frequency of cardiogenic shock was 2.3 % in the metoprolol group and 1.9 % in the placebo group in the subset of patients with low shock risk index. The corresponding excess frequency for patients in Killip class I was 0.7% (metoprolol 3.5% and placebo 2.8%). The shock risk index was based on the absolute risk of shock in each individual patient derived from age, sex, time delay, Killip class, blood pressure, heart rate, ECG abnormality, and prior history of hypertension. The patient group with low shock risk index corresponds to the patients in which metoprolol is indicated for use in acute myocardial infarction.

Section 10

New revision date of text: 10 January 2008

Reasons for adding or updating:

• Correction of spelling/typing errors

Reasons for adding or updating:

• Change to section 4.2 - Posology and method of administration
• Change to section 4.3 - Contraindications
• Change to section 4.4 - Special warnings and precautions for Use
• Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
• Change to section 4.6 - Pregnancy and Lactation
• Change to section 4.8 - Undesirable Effects
• Change to section 4.9 - Overdose
• Change to section 5.2 - Pharmacokinetic Properties
• Change to section 10 date of revision of the text
• Change from BAN to rINN

Date of revision of text on the SPC: 01-Mar-2007

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 4.2

Text added to 1st paragraph of section 4.2

The dose must always be adjusted to the individual requirements of the patient. The following are guidelines:

 

Control of Tachyarrhythmias changed to Cardiac arrhythmias.

I.V changed to intravenously             

 

Text added to 5th paragraph of section 4.2

Such treatment should be initiated in a coronary care or similar unit immediately after the patients haemodynamic condition has stabilised

           

 

Text added to 6^th paragraph of section 4.2

Impaired Renal Function: Dose adjustment is generally not needed in patients with impaired renal function.

 

Significant dysfunction changed to Impaired Hepatic Function

 

 

Existing text

A reduction in dosage may be necessary.

New text

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,

 

Text removed

according to the severity of hepatic impairment.

Existing text

Initially the lowest possible dose should be used, especially in the elderly

New text

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.

 

Existing text

There is limited experience with metoprolol treatment in children.

New text

The safety and efficacy of metoprolol in children has not been established.

 

 

 

 

Section 4.3

New text added

Betaloc Injection, as with other beta‑blockers, should not be used in patients with any of the following:

-         Hypotension,

-         AV block of second- or third‑degree,

Existing text

-         Uncontrolled heart failure Unstable

New text

-          Decompensated cardiac failure (pulmonary oedema, hypoperfusion or hypotension),

-         Continuous or intermittent inotropic therapy acting through beta‑receptor agonism,

 

 

Exisitng text

b-blockers or to any of the constituents of Betaloc i.v.

New text

any component of Betaloc Injection or other beta‑blockers

 

 

Section 4.4

Text removed

If patients develop increasing bradycardia, Betaloc i.v. should be given in lower doses or gradually withdrawn. Symptoms of peripheral arterial circulatory disorders may be aggravated by Betaloc.

 

In cases where the systolic blood pressure is below 100mmHg, Betaloc should only be given intravenously if special precautions are observed, because there is a risk that administration of the drug by this route may cause a further fall in blood pressure (i.e. in patients with cardiac arrhythmias).

 

Text added

When treating patients with suspected or definite myocardial infarction the haemodynamic status of the patient should be carefully monitored after each of the three 5mg intravenous doses. The second or third dose should not be given if the heart rate is <40 beats/min, the systolic blood pressure is <90mmHg and the P‑Q time is >0.26 sec, or if there is any aggravation of dyspnoea or cold sweating.

 

Betaloc, as with other beta‑blockers:

 

 

Text removed

Abrupt interruption of b-blockers is to be avoided.

Text added

should not be withdrawn abruptly during oral treatment. When possible, Betaloc should be withdrawn gradually over a period of 10‑14 days, in diminishing doses to 25mg daily for the last 6 days.

The risk for coronary events, including sudden death, may increase during the withdrawal of beta‑blockade.

 

New text added

It is not generally recommended to stop Betaloc 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.  However, in some patients it may be desirable to employ a beta-blocker as premedication.  By shielding the heart against the effects of stress, the beta-blocker may prevent excessive sympathetic stimulation provoking cardiac arrhythmias or acute coronary insufficiency.  If a beta-blocker is given for this purpose, 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 (see Section 4.3), may also aggravate less severe peripheral arterial circulatory disorders.

 

Betaloc should be used with caution in patients where cardiac reserve is poor.

 

may cause patients to develop increasing bradycardia, in such cases the Betaloc Injection dosage should be reduced or gradually withdrawn.

 

Existing text

may aggravate pre‑existing conduction time disorders of moderate degree, which may lead to AV block, and

New text

due to the negative effect on conduction time, should only be given with caution to patients with first-degree heart block.

 

 

Existing text

In patients with Prinzmetal’s angina b₁ selective agents should be used with care.

New text

may increase the number and duration of angina attacks in patients with Prinzmetal’s angina, due to unopposed alpha‑receptor mediated coronary artery vasoconstriction. Betaloc Injection is a beta₁‑selective beta‑blocker; consequently, its use may be considered although utmost caution must be exercised.

 

Exisiting text

As with other b-blockers, Betaloc i.v. may mask the symptoms of thyrotoxicosis and the early signs of acute hypoglycaemia in patients with diabetes mellitus. However, the risk of this occurring is less than with non-selective b-blockers.

New text

may mask the early signs of acute hypoglycaemia, in particular tachycardia. During treatment with Betaloc Injection, the risk of interfering with carbohydrate metabolism or masking hypoglycaemia is less than with non‑selective beta‑blockers.

 

New text added

may mask the symptoms of thyrotoxicosis.

 

 

New text added (bold)

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 Betaloc Injection is commenced.

 

Text removed

The elderly should be treated with caution, starting with a lower dose.

 

The administration of adrenaline to patients undergoing b-blockade can result in an increase in blood pressure and bradycardia although this is less likely to occur with b1-selective drugs.

 

 

Section 4.5

New text added

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.

 

Existing text

Plasma levels of metoprolol may be raised by co‑administration of compounds metabolised by CYP2D6, e.g. 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.

New text

Enzyme inducing agents (e.g. rifampicin) may reduce plasma concentrations of Betaloc i.v., whereas enzyme inhibitors (e.g. cimetidine, alcohol and hydralazine) may increase plasma concentrations.

 

 

Existing text

Care should also be exercised when b-blockers are given in combination with sympathomimetic ganglion blocking agents, other b-blockers (i.e. eye drops) or MAO inhibitors.

New text

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.

 

 

 

 

 

 

 

 

 

 

Exisiting text

Like all other b-blockers, Betaloc i.v.  should not be given in combination with verapamil, diltiazem or digitalis glycosides. A watch should be kept for possible negative effects when metoprolol is given in combination with calcium antagonists, since this may cause bradycardia, hypotension and asystole. 

New text

Increased negative inotropic and chronotropic effects may occur when Betaloc 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.

 

 

Text removed

Betaloc i.v. Injection can reduce myocardial contractility and impair intracardiac conduction.  Care should be exercised when drugs with similar activity, e.g. antiarrhythmic agents (of the quinidine type and amiodarone) or general anaesthetics, are given concurrently.

 

New text added

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.

 

The administration of adrenaline (epinephrine) to patients undergoing beta‑blockade can result in an increase in blood pressure and bradycardia although this is less likely to occur with beta₁‑selective drugs.

 

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.

 

 

New text

when combining with other antihypertensive drugs or drugs that might reduce blood pressure

Text removed

to avoid hypotension ould be the result of concomitant administration with dihydropyridine derivatives,

 

 

 

 

 

 

 

Section 4.6

 

Pregnancy added to beginning of section and metoprolol changed to Betaloc Injection.

 

text removed

Use during

 

 

Section 4.8

Text removed

Metoprolol is usually well tolerated and adverse reactions have generally been mild and reversible.

A relationship to treatment with metoprolol has not always been established.

 

 

New text added

As in the case of other b-blockers, a marked fall in blood pressure may sometimes occur following intravenous injection of Betaloc. Other side effects are usually mild and infrequent.  The most common appear to be lassitude, GI disturbances (nausea, vomiting or abdominal pain) and disturbances of sleep pattern.  In many cases these effects have been transient or have disappeared after a reduction in dosage.

 

 

Text removed

Effects related to the CNS which have been reported occasionally are dizziness and headache and rarely paraesthesia, muscle cramps, depression, decreased mental alertness.  There have also been isolated reports of personality disorders like amnesia, memory impairment, confusion, hallucination, nervousness and anxiety.

 

Cardiovascular effects which have been reported occasionally are bradycardia, postural hypotension and rarely, heart failure, increased existing AV block, palpitations, cardiac arrhythmias, Raynauds phenomenon, peripheral oedema and precordial pain.  There have also been isolated reports of cardiac conduction abnormalities, gangrene in patients with pre-existing severe peripheral circulatory disorders and increase of pre-existing intermittent claudication.

 

New text added

Common gastro-intestinal disturbances have been described above but rarely diarrhoea or constipation also occur and there have been isolated cases of dry mouth and abnormal liver function.

 

 

Text removed

Skin rashes (urticaria, psoriasiform, dystrophic skin lesions) and positive anti-nuclear antibodies (not associated with SLE) occur rarely.  Isolated cases of photosensitivity, psoriasis exacerbation,  increased sweating and alopecia have been reported.  Respiratory effects include occasional reports of dyspnoea on exertion and rare reports of bronchospasm and isolated cases of rhinitis.

 

New text added

Rarely impotence/sexual dysfunction.  Isolated cases of weight gain, thrombocytopenia, disturbances of vision, conjunctivitis, tinnitus, dry or irritated eyes, taste disturbance and arthralgia have also been reported.

 

Very common (>10%), common (1‑9.9%), uncommon (0.1‑0.9%), rare (0.01‑0.09%) and very rare (<0.01%).

 

Infections and infestations

Very rare:         Gangrene in patients with pre‑existing severe peripheral circulatory disorders.

 

Blood and lymphatic system disorders

Very rare:         Thrombocytopenia.

 

Psychiatric disorders

Uncommon:      Depression, insomnia, nightmares.

Rare:                Nervousness, anxiety.

Very rare:         Confusion, hallucinations.

 

Nervous system disorders

Common:         Dizziness, headache.

Uncommon:      Concentration impairment, somnolence, paraesthesiae.

Very rare:         Amnesia/memory impairment, taste disturbances.

 

Ear and labyrinth disorders

Very rare:         Tinnitus.

 

Cardiac disorders

Common:         Bradycardia, palpitations.

Uncommon:      Deterioration of heart failure symptoms, first‑degree heart block.

Rare:                Disturbances of cardiac conduction, cardiac arrhythmias, increased existing AV block.

 

Vascular disorders

Common:         Postural disorders (very rarely with syncope).

Rare:    Raynauds phenomenon.

Very rare:         Increase of pre-existing intermittent claudication.

 

Respiratory, thoracic and mediastinal disorders

Common:         Dyspnoea on exertion.

 

 

Gastrointestinal disorders

Common:         Nausea, abdominal pain, diarrhoea, constipation.

Uncommon:      Vomiting.

Rare:                Dry mouth.

 

Hepato-biliary disorders

Very rare:         Hepatitis.

 

Skin and subcutaneous tissue disorders

Uncommon:      Rash (in the form of psoriasiform urticaria and dystrophic skin lesions), increased sweating.

Rare:                Loss of hair.

Very rare:         Photosensitivity reactions, aggravated psoriasis.

 

Musculoskeletal and connective tissue disorders

Very rare:         Arthralgia.

Uncommon:      Muscle cramps.

 

Reproductive system and breast disorders

Rare:                Impotence/sexual dysfunction.

 

General disorders and administration site disorders

Very common: Fatigue.

Common:         Cold hands and feet.

Uncommon:      Precordial pain, oedema.

 

Investigations

Uncommon:      Weight gain.

Rare:                Liver function test abnormalities, positive anti-nuclear antibodies (not associated with SLE).

 

 

Section 4.9

 

Symptoms added to beginning of section 4.9

           

Text removed

Concomitant ingestion of alcohol, antihypertensives, quinidine, or barbiturates or other drugs and combinations of drugs that might negatively affect the circulatory system and/or the central nervous system, may aggravate the patient’s condition.

 

Text added

In the presence of severe hypotension, bradycardia, and impending heart failure, administer a beta₁‑agonist until the desired effect is achieved. Where a selective beta₁‑agonist is not available, dopamine may be used; or atropine sulphate i.v. may be used in order to block the vagus nerve. If a satisfactory effect is not achieved, other

Text removed

It should be noted that the dosages of drugs (antidotes) needed to treat overdose of beta‑blockade are much higher than normally recommended therapeutic dosages. This is because the beta‑receptors are occupied by the beta‑blocker.

 

Existing text

The use of haemodialysis or haemoperfusion may be considered.

New text

Betaloc Injection cannot be effectively removed by haemodialysis.

 

 

 

 

Section 5.2

New Text added

Metoprolol undergoes oxidative metabolism in the liver primarily by the CYP2D6 isoenzyme.

 

 

Section 10

Change date to 21^st March 2007

Reasons for adding or updating:

• Change to section 7 - Marketing Authorisation Holder
• Change to section 8 - MA number
• Change to section 9 - Date of Renewal of Authorisation

Reasons for adding or updating:

• Change to section 7 - Marketing Authorisation Holder

Reasons for adding or updating:

• No reasons supplied

Reasons for adding or updating:

• No reasons supplied

Reasons for adding or updating:

• No reasons supplied