This information is intended for employ by health professionals

Metoprolol Tartrate 100 mg tablets

Each tablet contains Metoprolol tartrate 100 mg

For a total list of excipients, see section 6.1.

Tablet

White to off-white, approximately 10 mm round, biconvex tablet marked on one side and a scoreline on the other side.

The tablet can be divided into equal halves.

In the management of:

• Hypertension

• Angina pectoris

• Cardiac arrhythmias(in particular supraventricular tachycardias)

• As an adjunctive treatment of thyrotoxicosis.

• Early on intervention of metoprolol tartrate in acute myocardial infarction reduces infarct size and the incidence of ventricular fibrillation. Pain relief may too decrease the need for opiate analgesics.

• long-term prophylaxis afterwards recovery from acute myocardial infarction.

• Prophylaxis of migraine

Metoprolol tartrate has been shown to reduce mortality when administered to patients with astute myocardial infarction.

Metoprolol is indicated in adults.

Posology

The following dosage regimes are intended only as a guideline and should always be adjusted to the private requirements of the patient but should not exceed 400 mg/twenty-four hour period.

Adults

Hypertension

Initially 100mg daily. This may exist increased, if necessary, to 200mg daily in unmarried or divided doses. Combination therapy with a diuretic or vasodilator may also be considered to further reduce blood pressure.

Metoprolol may exist 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 added in to the regime with aligning of the previous therapy if necessary.

Angina pectoris

Usually l-100 mg two or three times daily. In general a significant improvement in exercise tolerance and reduction of angina attacks may be expected with a dose of 50-100mg twice daily.

Cardiac arrhythmias

50mg ii or three times daily is usually sufficient. If necessary the dose may exist increased to 300mg daily in divided doses.

Post-obit the treatment of an acute arrhythmia with metoprolol tartrate injection, continuation therapy with metoprolol tablets should exist initiated 4-6 hours later. The initial oral dose should not exceed 50mg twice daily.

Myocardial infarctions

Early intervention

Orally, therapy should commence 15 minutes after the last intravenous injection with 50mg every 6 hours for 48 hours and preferably within 12 hours of the onset of chest pain. Patients who neglect to tolerate the full i.v. dose should be given half the suggested oral dose.

Maintenance

The usual maintenance dose is 200 mg daily given in divided doses. The handling should be continued for at to the lowest degree 3 months.

Thyrotoxicosis

50mg four times daily. Dose should be reduced progressively as euthyroid country is achieved.

Prophylaxis of migraine

100 - 200 mg daily in divided doses (forenoon and evening).

Elderly

The optimum dose should be individually determined co-ordinate to clinical response. There is no show to suggest that dosage requirements are different in otherwise salubrious elderly patients. However, caution is indicated in elderly patients as an excessive decrease in blood pressure level or pulse charge per unit may crusade the claret supply to vital organs to fall to inadequate levels. Dosage should exist reduced in the elderly where there is impairment of hepatic function.

Paediatric population

The safety and efficacy of Metoprolol in children has non been established. Metoprolol tartrate is not recommended in children.

Hepatic impairment

In patients with significant hepatic dysfunction dosage reduction may be brash.

Renal impairment

Dose adjustment is non warranted in renal impairment.

Method of Administration

For oral administration.

• Known hypersensitivity to metoprolol, related derivatives, any other β-blockers or to whatever of the excipients listed in department 6.1.

• Second-or third-caste atrioventricular cake

• Uncontrolled centre failure

• Clinically relevant sinus bradycardia (< 45-50 bpm)

• Sick sinus syndrome(unless a pacemaker is in situ).

• Prinzmetal's angina

• Myocardial infarction complicated by significant bradycardia, first degree centre block, systolic hypotension (less than 100mmHg) and/or severe heart failure and cardiogenic shock

• Astringent peripheral arterial disease

• Asthma and history of bronchospasm

• Untreated phaeochromocytoma

• Metabolic acidosis

• Concomitant intravenous administration of calcium blockers of the type verapamil or diltiazem or other antiarrhythmics (such as disopyramide) is contraindicated (exception: intensive intendance unit).

• Hypotension

• Diabetes if associated with frequent episodes of hypoglycaemia

• Chronic obstructive pulmonary disease

Abrupt cessation of therapy with a beta-blocker should be avoided especially in patients with ischaemic centre affliction. 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 aforementioned fourth dimension, initiating replacement therapy, to preclude exacerbation of angina pectoris. In addition, hypertension and arrhythmias may develop. When it has been decided to interrupt a beta-blockade in grooming for surgery, therapy should be discontinued for at to the lowest degree 24 hours. Continuation of beta-occludent reduces the risk of arrhythmias during induction and intubation, withal the gamble 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 confronting vagal reactions by intravenous assistants of atropine. During its withdrawal the patient should be kept nether shut surveillance.

Although cardioselective beta blockers may have less effect on lung function than not 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, information technology is advisable to exercise care in the treatment of patients with chronic obstructive pulmonary disease. Therapy with a betatwo-stimulant may go necessary or current therapy require aligning. Therefore, non selective beta blockers should non exist used for these patients, and betai-selective blockers only with the utmost care.

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

Metoprolol Tartrate tablets may non be administered to patients with untreated congestive heart failure. The congestive centre 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 at that place is therefore a risk of AV dissociation. In addition, balmy cardiovascular complications may occur, manifesting as dizziness, bradycardia, and a tendency to plummet.

When a beta blocker is existence taken, a serious, sometimes even life-threatening deterioration in cardiac office can occur, in particular in patients in whom the activeness of the eye is dependent on the presence of sympathetic arrangement support. This is due less to an excessive beta-blocking effect and more to the fact that patients with marginal centre function tolerate poorly a reduction in sympathetic nervous system action, even where this reduction is slight. This causes contractility to get weaker and the heart charge per unit to reduce and slows downward AV conduction. The consequence of this can exist pulmonary oedema, AV block, and daze. Occasionally, an existing AV conduction disturbance tin can deteriorate, which can pb to AV cake.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 information technology 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 circumspection to patients having, or suspected of developing, thyrotoxicosis, and both thyroid and cardiac function should exist monitored closely

Simultaneous assistants of adrenaline (epinephrine), noradrenaline (norepinephrine) and β blockers may lead to increment in blood pressure level and bradycardia.

Metoprolol may induce or aggravate bradycardia, symptoms of peripheral arterial circulatory disorders and anaphylactic stupor. If the pulse rate decreases to less than l-55 beats per minute at rest and the patient experiences symptoms related to the bradycardia, the dosage should be reduced.

Metoprolol may be administered when middle failure has been controlled. Digitalisation and/or diuretic therapy should also exist 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 sugar 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 nonselective beta blockers. In labile and insulin-dependent diabetes, information technology may be necessary to accommodate the hypoglycaemic therapy.

In case of unstable or insulindependent 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 information technology may be necessary to adjust the dosage because metoprolol undergoes biotransformation in the liver. Patients with hepatic or renal insufficiency may demand a lower dosage, and metoprolol is contraindicated in patients with hepatic or renal disease/failure (encounter section 4.iii). The elderly should exist treated with caution, starting with a lower dosage simply tolerance is usually good in the elderly. Information technology may exist necessary to employ a lower strength formulation in elderly patients and patients with hepatic or renal impairment and an culling production should exist prescribed.

Patients with anamnestically known psoriasis should have beta-blockers merely after careful consideration every bit the medicine may cause aggravation of psoriasis.

Beta blockers may increase both the sensitivity towards allergens and the seriousness of anaphylactic reactions. Adrenaline (epinephrine) handling does not always give the desired therapeutic issue 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 adapted accordingly.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose galactose mal-assimilation should not take this medicine.

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

- Anaesthetic drugs may attenuate reflex tachycardia and increase the risk of hypotension. Metoprolol therapy should be reported to the anaesthetist before the administration of a general anaesthetic. If possible, withdrawal of metoprolol should exist completed at least 48 hours before amazement. Yet, for some patients undergoing elective surgery, it may exist desirable to employ a beta-blocker as premedication. By shielding the center against the effect of stress, metoprolol may prevent excessive sympathetic stimulation which is liable to provoke such cardiac disturbance as arrhythmias or astute coronary insufficiency during induction and intubation. Anaesthetic agents causing myocardial low, such every bit cyclopropane and trichlorethylene, are best avoided. In a patient under beta-blockade an anaesthetic with as piddling negative inotropic activity as possible (halothane/nitrous oxide) should be selected.

- It may be necessary to conform the dose of the hypoglycaemic amanuensis in labile or insulin-dependent diabetes. Beta-adrenergic occludent may prevent the appearance of signs of hypo-glycaemia (tachycardia).

- Like all beta-blockers, metoprolol should not exist given in combination with calcium aqueduct blockers i.eastward. verapamil and to a bottom extent diltiazem since this may cause bradycardia, hypotension, heart failure and asystole and may increase auriculoventricular conduction fourth dimension. Nevertheless, combinations of antihypertensive drugs may often be used with do good to improve control of hypertension. Calcium blockers of the verapamil blazon should non be administered intravenously to patients receiving beta blockers (see section iv.iii).

- Intendance should also be taken when beta-blockers are given in combination with sympathetic ganglion blocking agents, other beta blockers or MAO inhibitors. Concomitant administration of tricyclic antidepressants, barbiturates and phenothiazines as well as other antihypertensive agents may increase the claret pressure lowering effect.

- Calcium aqueduct blockers (such as dihydropyridine derivatives due east.g. nifedipine) should not be given in combination with metoprolol because of the increased adventure of hypotension and heart failure. In patients with latent cardiac insufficiency, handling with beta-blocking agents may pb to cardiac failure. Beta-blockers used in conjunction with clonidine increment the risk of "rebound hypertension". If combination treatment with clonidine is to be discontinued, metoprolol should exist withdrawn several days earlier clonidine.

- The furnishings of metoprolol and other antihypertensive drugs on claret pressure are unremarkably additive, and care should exist taken to avoid hypotension.

- NSAIDs (especially indometacin) may reduce the antihypertensive furnishings of beta-blockers possibly past inhibiting renal prostaglandin synthesis and/or causing sodium and fluid retention.

- Digitalis Glycosides and/or diuretics should be considered for patients with a previous history of centre failure or in patients known to have a poor cardiac reserve. Digitalis glycosides in clan with beta-blockers may increase in auriculo-ventricular conduction fourth dimension.

- The administration of adrenaline (epinephrine) or noradrenaline (norepinephrine) to patients undergoing beta-blockade can result in an increase in blood force per unit area and bradycardia, although this is less probable to occur with beta1-selective drugs. As beta-blockers may bear upon the peripheral apportionment, intendance should be exercised when drugs with similar activity e.g. ergotamine are given

concurrently. Concurrent apply of moxisylyte may effect in possible severe postural hypotension.

- The effect of adrenaline (epinephrine) in the treatment of anaphylactic reactions may be weakened in patients receiving beta blockers (see likewise section 4.4).

- Metoprolol will antagonise the beta1-furnishings of sympathomimetic agents but should accept niggling influence on the bronchodilator effects of beta2-agonists at normal therapeutic doses.

- Enzyme inducing agents (due east.chiliad. rifampicin) may reduce plasma concentrations of metoprolol, whereas enzyme inhibitors (e.g. cimetidine, hydralazine and alcohol), selective serotonin reuptake inhibitors (SSRIs) as paroxetine, fluoxetine and sertraline, diphenhydramine, hydroxychloroquine, celecoxib, terbinafine may increase plasma concentrations of hepatically metabolized beta blockers.

- As with all beta-blockers detail caution is called for when metoprolol is administered together with prazosin for the first time as the co-administration of metoprolol and prazosin may produce a first dose hypotensive outcome.

- Class ane antiarrhythmic drugs, east.thousand. disopyramide, quinidine and amiodarone may have potentiating furnishings on atrialconduction time and induce negative inotropic effect. Concurrent utilize of propafenone may result in significant increases in plasma concentrations and halflife of metoprolol. Plasma propafenone concentrations are unaffected. Dosage reduction of metoprolol may be necessary.

- During concomitant ingestion of booze and metoprolol the concentration of blood booze may attain college levels and may decrease more slowly. The concomitant ingestion of alcohol may enhance hypotensive effects.

- Metoprolol may impair the emptying of lidocaine.

- Prostaglandin synthetase inhibiting drugs may decrease the hypotensive effects of beta-blockers.

- Concurrent apply of oestrogens may decrease the antihypertensive issue of beta-blockers because oestrogeninduced fluid retention may lead to increased blood pressure.

- Concurrent use of xanthines, specially aminophylline or theophylline, may event in mutual inhibition of therapeutic furnishings.

- Xanthine clearance may also be decreased especially in patients with increased theophylline clearance induced by smoking.

- Concurrent use requires careful monitoring.

- Concurrent utilise of aldesleukin may issue in an enhanced hypotensive result.

- Concurrent employ of alprostadil may consequence in an enhanced hypotensive effect.

- There is an increased hazard of bradycardia following concomitant utilise of mefloquine with metoprolol.

- Concomitant use with anxiolytics and hypnotics may result in an enhanced hypotensive issue.

- Concomitant use with corticosteroids may result in animosity of the hypotensive effect.

- The manufacturer of tropisetron advises caution in concomitant administration due to the risk of ventricular arrhythmias.

Pregnancy

It is recommended that metoprolol should not exist administered during pregnancy or lactation unless information technology is considered that the benefit outweighs the possible take a chance to the foetus/baby. Should therapy with metoprolol exist employed, special attention should be paid to the foetus, neonate and breast fed infant for any undesirable effects such equally slowing of the center rate.

Metoprolol has, however, been used in pregnancy associated hypertension under shut supervision later 20 weeks gestation. Although the drug crosses the placental barrier and is present in string blood no testify of foetal abnormalities has been reported. Even so, there is an increased take a chance of cardiac and pulmonary complications in the neonate in the postnatal period.

Beta blockers reduce placental perfusion and may crusade foetal death and premature birth. Intrauterine growth retardation has been observed later on longtime treatment of significant women with mild to moderate hypertension. Beta blockers take been reported to cause bradycardia in the foetus and the newborn kid, there are also reports of hypoglycaemia and hypotension in newborn children.

Fauna experiments accept shown neither teratogenic potential nor other adverse events on the embryo and/or foetus relevant to the safety assessment of the product. Handling with metoprolol should be discontinued 48-72 hours before the calculated birth date. If this is not possible, the newborn child should exist monitored for 24-48 hours post partum for signs and symptoms of beta blockade (east.thou. cardiac and pulmonary complications).

Lactation

The concentration of metoprolol in breast milk is approximately three times college than the 1 in the mother's plasma. The risk of agin effects in the breastfeeding infant would appear to be low later assistants of therapeutic doses of the medicinal product (except in individuals with poor metabolic capacity). Cases of neonatal hypoglycaemia and bradycardia have been described with beta-blockers with low plasma protein bounden. Metoprolol is excreted in human being milk. Fifty-fifty though the metoprolol concentration in milk is very low, chest-feeding should be discontinued during treatment with metoprolol. In case of treatment during breast feeding, infants should be monitored carefully for symptoms of beta occludent.

As with all beta-blockers, metoprolol can affect patient'south power to drive and operate machinery. It should exist taken into account that occasionally dizziness and fatigue may occur. Patient should be warned accordingly. If affected, patients should non drive or operate machinery.

Frequency estimates: Very common (≥one/10); common (≥1/100 to <i/x); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<ane/ten,000); not known (cannot be estimated from the available data)

System Organ Class

Very common (≥one/x)

Common (≥1/100 to <one/10)

Uncommon (≥one/one,000 to <1/100)

Rare (≥1/10,000 to <1/1,000)

Very rare (<i/10,000)

Not known (cannot be estimated from the bachelor data)

Blood and lymphatic arrangement disorders

Thrombocytopenia, agranulocytosis

Psychiatric disorders

Depression, nightmares, Nervousness, anxiety, impotence

Hallucinations, personality disorder, Amnesia / retentiveness harm

Nervous system disorders

Dizziness, headache

Alertness decreased, somnolence or insomnia, paraesthesia

Centre disorders

Visual disturbance (east.thou. blurred vision, dry eyes and/or eye irritation

Ear and labyrinth disorders

Tinnitus, and, in doses exceeding those recommended, "hearing disorders (eg. hypoacusis or deafness)

Cardiac disorders

Bradycardia

Heart failure, cardiac arrhythmias, palpitation

Cardiac conduction disorders, precordial pain

Increase in existing intermittent claudication

Vascular disorders

Orthostatic hypotension (occasionally with syncope)

Oedema, Raynaud's phenomenon

Gangrene in patients with pre existing severe peripheral circulatory disorders

Respiratory, thoracic and mediastinal disorders

Exertional dyspnoea

Bronchospasm(which may occur in patients without a history of obstructive lung illness)

Rhinitis

Gastrointestinal disorders

Nausea and vomiting, intestinal pain

Diarrhoea or constipation

Dry mouth

Retroperitoneal fibrosis *

Hepatobiliary disorders

Hepatitis

Skin and subcutaneous tissue disorders

Peel rash (in the grade of urticaria, psoriasiform and dystrophic skin lesions) southward

Photosensitivity, hyperhidrosis, alopecia, worsening of psoriasis

Occurrence of antinuclear antibodies (non associated with SLE)

Musculoskeletal and connective tissue disorders

Muscle cramps

Arthritis

Reproductive system and breast disorders

Disturbances of Libido and dominance

Peyronie's illness *

General disorders and administration site atmospheric condition

Fatigue

Dysgeusia (Gustatory modality disturbances)

Investigations

Weight increase, liver function test abnormal

* (relationship to Metoprolol has not been definitely established).

Beta-blockers may mask the symptoms of thyrotoxicosis or hypoglycaemia.

Postal service Marketing Experience

The post-obit 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, information technology is not possible to reliably gauge their frequency.

Reporting of suspected agin reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/take chances residue of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Xanthous Card Scheme

Website: world wide web.mhra.gov.uk/yellowcard or search for MHRA Yellowish Carte du jour in the Google Play or Apple App Store.

Poisoning due to an overdose of metoprolol may pb to astringent hypotension, sinus bradycardia, atrioventricular block, center failure, cardiogenic shock, cardiac arrest, bronchospasm, harm of consciousness, coma, nausea, vomiting, cyanosis, hypoglycaemia and, occasionally, hyperkalaemia. The get-go manifestations usually appear 20 minutes to two hours afterward drug ingestion.

After ingestion of an overdose or in case of hypersensitivity, the patient should be kept nether close supervision and exist treated in an intensive- care ward. Absorption of any drug material still nowadays in the gastrointestinal tract can be prevented by induction of airsickness, gastric lavage, administration of activated charcoal and a laxative. Bogus respiration may be required.

Bradycardia or all-encompassing vagal reactions should be treated past administering atropine or methylatropine. Hypotension and shock should be treated with plasma/plasma substitutes and, if necessary, catecholamines. The beta-blocking issue can be counteracted past slow intravenous administration of isoprenaline hydrochloride, starting with a dose of approximately v micrograms/minute, or dobutamine, starting with a dose of 2.5micrograms/infinitesimal, until required upshot has been obtained. In refractory cases isoprenaline can be combined with dopamine. If this does not produce the desired upshot either, intravenous administration of 8-10mg glucagon may be considered. If required the injection should exist repeated inside i hour, to be followed – if required – past an i.v. infusion of glucagon at an administration rate of i-3mg/hour. Administration of calcium ions , or the use of a cardiac pacemaker may also be considered. In patients intoxicated with hydrophilic beta-blocking agents haemodialysis or haemoperfusion may exist considered.

Pharmacotherapeutic category: Beta blocking agents, selective,

ATC code: C07AB02

Mechanism of action

Metoprolol tartrate is a cardioselective beta-adrenergic blocking agent. It has a relatively greater blocking effect on betai-receptors (ie those mediating adrenergic stimulation of heart rate and contractility and release of free fatty acids from fatty stores) than on betaii-receptors, which are chiefly involved in broncho and vasodilation.

Absorption

Metoprolol is readily and completely absorbed from the gastrointestinal tract. Metoprolol is absorbed fully after oral administration. Inside the therapeutic dosage range, the plasma concentrations increase in a linear manner in relation to dosage. Peak plasma levels are achieved after approx. one.v–2 hours. Even though the plasma profile displays a broader interindividual variability, this appears to be easily reproducible on an individual basis. Due to the extensive offset-pass effect, bioavailability after a single oral dose is approx. 50%. After repeated administration, the systemic availability of the dose increases to approx. 70%. After oral intake with food, the systemic availability of an oral dose increases by [SIC] approx. 30–40%.

Distribution

Acme plasma concentrations occur almost 1½ hours after a single oral dose. Height plasma metoprolol concentrations at steady country with usual doses take been reported every bit twenty-340ng/ ml. Metoprolol is widely distributed, it crosses the bloodbrain barrier, the placenta. It is slightly jump to plasma protein. The medicinal product is approx. 5–10% bound to plasma proteins.

Biotransformation

Metoprolol is metabolised through oxidation in the liver mainly past the CYP2D6 isoenzyme. Even though iii main metabolites have been identified, none of them has a clinically pregnant beta-blocking effect. Generally, 95% of an oral dose is found in the urine. Only 5% of the dose is excreted unmodified via the kidneys; in isolated cases, this effigy tin can achieve as high as xxx%. The emptying half-life of metoprolol averages 3.v hours (with extremes of 1 and 9 hours). Total clearance is approx. ane litre/minute. It is extensively metabolised in the liver; O-dealkylation followed by oxidation and aliphatic hydroxylation. The charge per unit of hydroxylation to blastoff-hydroxymetoprolol is reported to be determined by genetic polymorphism; the half-life of metoprolol in fast hydroxylators is stated to exist 3-4 hours, whereas in poor hydroxylators information technology is about 7 hours.

Elimination

The metabolites are excreted in the urine together with but minor amounts of unchanged metoprolol. Metoprolol is excreted in chest milk.

Special population

Elderly:

In comparison with administration to younger patients, the pharmacokinetics of metoprolol when administered to older patients shows no significant differences.

Renal impairment:

Renal dysfunction has barely any issue on the bioavailability of metoprolol. All the same, the excretion of metabolites is reduced. In patients with a glomerular filtration rate of less than five ml/minute, a significant accumulation of metabolites has been observed. This aggregating of metabolites, however, produces no increase in the beta occludent.

Hepatic impairment:

The pharmacokinetics of metoprolol are influenced merely minimally past reduced hepatic function. Even so, in patients with serious hepatic cirrhosis and a portacaval shunt, the bioavailability of metoprolol can increment, and the full clearance can be reduced. Patients with portacaval anastomosis had a total clearance of approx. 0.3 litres/minute and AUC values that were 6 times higher than those establish in healthy persons.

Severe angina pectoris

Intrinsic sympathomimetic activeness (ISA) may exist a disadvantage for the patient with astringent angina pectoris. At that place are however no indications that the efficacy in hypertensives is influenced by this feature. In exceptional cases, notwithstanding, very loftier dosages can cause the ISA to predominate over the beta-adrenergic blocking chapters so that restriction of the maximum dosage is indicated.

Respiratory impairment

It has not been proven that beta-blockers with ISA give a lower take chances for bronchospasm or enhancement of preexisting bronchospastic complaints.

There are no preclinical data of relevance to the prescriber which are boosted to that already included in other sections of the SPC.

Cellulose, microcrystalline (E460)

Gelatin (E441)

Sodium starch glycolate

Silica, colloidal hydrated (E551)

Stearic acid

Not applicable

3 years

Do not store above 25°C.

Tablets are packed in PVC/PVdC-Aluminium blisters containing 10, xx, 28, 30, 50, 56, 60, 84 and 90 tablets.

Not all pack sizes may be marketed.

No special requirements.

Any unused production or waste material should exist disposed of in accord with local requirements.

Accord Healthcare Limited

Sage House, 319, Pinner Road

North Harrow

Middlesex HA ane iv HF

United kingdom of great britain and northern ireland

PL 20075/0305

23/09/2011

08/03/2019