Bedranol 160mg SR Capsules

1. Name Of The Medicinal Product

Bedranol* (Propranolol Hydrochloride) SR Capsules 160mg[1].

2. Qualitative And Quantitative Composition

Each capsule contains propranolol hydrochloride BP 160mg.

3. Pharmaceutical Form

Sustained release capsule.

4. Clinical Particulars

4.1 Therapeutic Indications

a) Control of hypertension.

b) Management of angina.

c) Prophylaxis of migraine.

d) Management of essential tremor.

e) Management of anxiety.

f) Adjunctive management of thyrotoxicosis.

g) Prophylaxis of upper gastro-intestinal bleeding in patients with portal hypertension and oesophageal varices.

4.2 Posology And Method Of Administration

Adults:

(i) Hypertension

The initial dose is usually 160mg daily taken orally in the morning or evening. An adequate response is seen by most patients at this dosage. If necessary the dose can be increased to 320mg. A further reduction in blood pressure may be achieved by combining Bedranol* SR with other anti-hypertensive agents.

(ii) Angina, essential tremor, thyrotoxicosis, and the prophylaxis of migraine

The usual dose is 80mg daily, taken orally in the morning or evening. The dose may be increased to 160mg, and then if necessary further increased to 240mg per day.

(iii) Situational and generalised anxiety

A daily dose of one Bedranol* SR 80 mg Capsule should be sufficient to provide short-term relief of acute situational anxiety. Generalised anxiety, requiring longer term therapy, usually responds adequately at the same dosage. In some case the dosage may be increased to 160 mg. Patients should be reviewed after 6 – 12 months of treatment.

(iv) Portal hypertension

Dosage should be aimed to achieve approximately 25% reduction in resting heart rate. Dosing should initiated at 80 mg increasing to 160 mg depending on heart rate response. Further 80 mg increments may be added up to a maximum dose of 320 mg once daily.

Elderly patients:

The evidence concerning the relationship between blood level and age is conflicting. For patients already established on 160mg propranolol daily, one capsule of Bedranol* SR may be given. It is suggested that elderly patients being started off on propranolol treatment may need smaller initial doses and in these circumstances an alternative preparation should be used.

Children:

Bedranol* SR is not suitable for use in children.

Method of administration: Oral.

4.3 Contraindications

Bedranol* SR must not be used if any of the following conditions are present:

• hypersensitivity to propranolol or any of the other ingredients

• a history of bronchospasm or asthma

• bradycardia

• second or third degree heart block

• sick sinus syndrome

• cardiogenic shock

• uncontrolled heart failure

• hypotension

• severe peripheral arterial disease

• Prinzmetal's angina

• untreated phaeochromocytoma

• prolonged fasting, or prone to hypoglycaemia

• metabolic acidosis.

4.4 Special Warnings And Precautions For Use

Patients with a history of wheezing or asthma should not take propranolol unless it is considered essential. The label will carry the following warning: “Do not take this medicine if you have a history of wheezing or asthma.”. The patient information leaflet will state “Do not take this medicine if you have a history of wheezing or asthma. Consult your doctor or pharmacist first.”.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Intolerance to propranolol, shown as bradycardia and hypotension may occur, in which case propranolol should be withdrawn. If necessary, treatment for overdose should be started.

Beta-blockers may increase both the sensitivity towards allergens and the seriousness of anaphylactic reactions, they also may make patients less responsive to doses of adrenaline used to treat the allergic reactions.

Withdrawal of the drug for any reason should be gradual.

In patients with ischaemic heart disease treatment must not be discontinued abruptly. Either the equivalent dose of another beta-blocker may be substituted, or the withdrawal of Bedranol* SR should be gradual. This can be carried out by substituting the equivalent dose in propranolol 40mg tablets and then reducing the dose.

Bedranol* SR should be used with caution in patients whose cardiac reserve is poor.

Bedranol* SR may aggravate peripheral arterial circulatory disturbances.

As propranolol has a negative effect on conduction time, care must be taken when giving it to patients with first degree heart block.

Care must be taken in patients with renal or hepatic dysfunction when beginning treatment and choosing the initial dose.

Bedranol* SR should be used with care in patients with decompensated cirrhosis.

In patients with portal hypertension, liver function may deteriorate. There have been reports that treatment with propranolol may increase the risk of developing hepatic encephalopathy.

Propranolol, as with other beta-blocking drugs may block the symptoms of hypoglycaemia (especially tachycardia). It may even cause hypoglycaemia in non-diabetic patients e.g. neonates, infants, children, elderly patients, patients on haemodialysis or patients suffering from chronic liver disease and patients suffering from overdose. It has rarely caused seizures and/or coma in isolated patients. Caution should be exercised in the concurrent use of propranolol therapy in diabetic patients as it may prolong the hypoglycaemic response to insulin.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Care should be taken when prescribing beta-adrenoceptor blocking drugs with Class 1 antidysrhythmic agents there is an increased risk of myocardial depression and bradycardia, there is also an increased risk of lidocane toxicity. The antidysrhythmic propafenone increases plasma concentration of propranolol.

Beta-adrenoceptor blocking drugs should be used with caution in combination with calcium channel blockers such as verapamil or diltiazem in patients with impaired ventricular function. These should not be given to patients with conduction abnormalities. Beta-blockers or calcium channel blockers should not be given intravenously within 48 hours of discontinuing either one or the other.

Use with nifedipine or other dihydropyridines may cause an increased risk of hypotension, and heart failure may occur in patients with undiscovered cardiac insufficiency.

Propranolol modifies the tachycardia of hypoglycaemia and care should be taken when treating diabetic patients with Bedranol* SR whether or not they are also taking hypoglycaemic agents. Propranolol may prolong the hypoglycaemic response to insulin.

Use of adrenaline or other sympathomimetics with propranolol may counteract the effect of propranolol. Care should be taken in giving parenteral administration of adrenaline to patients taking beta-blocking drugs as, rarely, vasoconstriction, hypertension and bradycardia may result.

Rebound hypertension which can follow after withdrawal of clonidine may be exacerbated by beta-blockers. Therefore, if the patient is transferring from clonidine to propranolol, the latter treatment should be started several days after clonidine has been stopped. If Bedranol* SR and clonidine are given together, clonidine should be discontinued several days after stopping treatment with Bedranol* SR.

Digitoxin or digoxin taken at the same time as beta-blockers can increase atrioventricular conduction time.

Ergotamine, dihydroergotamine or related compounds given with propranolol have resulted in reports of vasospastic reactions in some patients.

The hypotensive effects of propranolol may be decreased if the patient also takes prostaglandin synthetase inhibitors, e.g. ibuprofen or indometacin.

If propranolol is taken with chlorpromazine, plasma levels of both agents may be increased, leading to enhanced antipsychotic and elevated antihypertensive effects.

Concomitant administration of rifampicin with propranolol may result in reduced plasma concentrations of propranolol. Thyroxine taken at the same time as propranolol also has this effect.

Cimetidine taken at the same time as propranolol will increase propranolol plasma levels. Fluvoxamine taken with propranolol also has this effect.

Alcohol enhances hypotensive effect.

It may be necessary to withdraw Bedranol* SR before surgery (24 hours should be allowed to elapse between the last dose and anaesthesia). If Bedranol* SR is continued throughout surgery the anaesthetist should be told and care should be taken in selecting and using suitable anaesthetic agents (note bupivacaine toxicity with propranolol)). An anaesthetic agent with as little myocardial depression as possible should be used. Beta-blockers used with anaesthesic agents may result in attenuation of reflex tachycardia and the risk of hypotension may increase.

Propranolol may affect lignocaine infusion by increasing the plasma concentration of lignocaine by approximately a third and therefore this should be avoided.

ACE inhibitors and Angiotensin-II Antagonists taken at the same time as propranolol may result in enhanced hypotensive effects. Aldesleukin and Alprostadil also has this effect.

Concomitant administration of corticosteroid may result in antagonism of hypotensive effect.

Propranolol may increase plasma concentration of rizatriptan when taken concomitantly.

Beta blockers including propranolol when taken with moxisylyte may result in severe postural hypotension

Concomitant administration of muscle relaxants may result in enhanced hypotensive effect.

Oestrogen and progestrogens, as used in the contraceptive pill, when taken with propranolol may antagonise the hypotensive effect.

The manufacturer of tropisetron advises caution for the co-administration with propranolol.

The concomitant administration of xamoterol with propranolol may result in a reduction in the beta-blockade.

Parasympathomimetics when used with propranolol increase the possibility of arrhythmias.

Interference with laboratory tests: Propranolol has been reported to interfere with the estimation of serum bilirubin by the diazo method and with the determination of catecholamines by methods using fluorescence.

4.6 Pregnancy And Lactation

Although there is no evidence that propranolol is teratogenic Bedranol* SR should not be used in pregnancy unless absolutely necessary. Beta-blockers reduce placental perfusion which may result in intra-uterine foetal death, immature or premature deliveries. Bradycardia may occur in the foetus and there may be an increased risk of cardiac and pulmonary problems in the post-natal period. Hypoglycaemia or bradycardia may occur in the neonate.

Breast-feeding is not recommended as beta-blockers taken by the mother will pass into the breast-milk.

4.7 Effects On Ability To Drive And Use Machines

Bedranol* SR should not impair ability to drive and use machines. However, sometimes dizziness or tiredness may occur. If so, the patient should not drive or operate machines.

4.8 Undesirable Effects

The following undesirable effects may occur.

Cardiovascular: deterioration of heart failure, bradycardia, postural hypotension with or without syncope may occur. Heart block, intermittent claudication or Raynaud's phenomenon may be precipitated or exacerbated. Cold extremities may occur.

Central nervous system: dizziness, confusion, mood changes, depression or psychosis and hallucinations, sleep disturbances or nightmares may occur.

Special senses: reports of visual disturbances, conjunctivitis or dry eyes have been made.

Peripheral nervous system: peripheral neuropathy or myopathies or paraesthesia may occur.

Gastrointestinal: GI disturbance including nausea, vomiting, diarrhoea, constipation or abdominal cramps have been reported.

Haematological: thrombocytopenia, purpura and rarely agranulocytosis. Eosinophilia may occur which passes quickly.

Hepatic: propranolol treatment may increase the risk of developing hepatic encephalopathy.

Respiratory: bronchospasm may occur in patients with bronchial asthma or a history of asthma. Fatalities have been reported.

Skin and hair: exacerbation of psoriasis, psoriasiform skin reactions, skin rashes, pruritus, or alopecia may occur.

Endocrine: hypoglycaemia in neonates, infants, children, elderly patients, patients on haemodialysis, patients on concomitant anti-diabetic therapy, patients with prolonged fasting and patients with chronic liver disease has been reported (see section 4.3, 4.4, 4.5).

Miscellaneous: headache, sexual dysfunction,fatigue (commonly), lassitude (often passing quickly), and an increase in antinuclear antibodies have been observed. There have been isolated reports of a myasthenia gravis-like syndrome or aggravation of myasthenia gravis.

Intolerance to propranolol, shown as bradycardia and hypotension may occur, in which case propranolol should be withdrawn. If necessary, treatment for overdose should be started.

Propranolol should be discontinued gradually if the patient's well-being is adversely affected by any undesirable effects.

4.9 Overdose

Symptoms of overdose: bradycardia, hypotension, bronchospasm and acute cardiac insufficiency.

General supportive measures should be employed such as gastric lavage, activated charcoal and a laxative to stop any remaining drug being absorbed. Shock treatment, if required should be given. Excessive bradycardia may be countered with 1-2mg IV atropine, followed if necessary by glucagon 10mg IV. This may be repeated, or followed by an intravenous infusion of glucagon 1-10mg/hour according to response. Alternatively, a beta-receptor stimulant such as isoprenaline 25mcg IV, orciprenaline 500mcg (0.5mg) IV or dobutamine 2.5-10mcg/kg/minute IV may be given.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Propranolol is a competitive blocker of beta-adrenergic receptor sites.

5.2 Pharmacokinetic Properties

Following oral administration Bedranol* SR peak plasma levels occur approximately 7 to 8.5 hours after an oral dose. Individual plasma concentrations vary. The plasma half-life of propranolol is about 3 to 6 hours. Propranolol binds well to plasma proteins. It has high lipid solubility, and crosses the blood-brain barrier, placenta and enters breast milk.

Propranolol is absorbed almost completely from the gastrointestinal tract, but binds to hepatic tissue where it is subject to first-pass metabolism.

Propranolol is metabolised in the liver, and excreted in the urine as metabolites and unchanged drug.

5.3 Preclinical Safety Data

There are no preclinical safety data of relevance to the prescriber.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Capsule contents:

Sucrose

Corn starch

Shellac

Talc

Capsule shell:

Gelatin

Titanium dioxide (E171)

Erythrosine (E127)

Printing ink:

Shellac

Black iron oxide (E172)

Propylene glycol

6.2 Incompatibilities

Not known.

6.3 Shelf Life

36 months.

6.4 Special Precautions For Storage

Store in a cool dry place and protect from light.

6.5 Nature And Contents Of Container

Polypropylene securitainers with polyethylene closures. Pack sizes[2]: 28, 30, 56, 60 and 100.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Sandoz Ltd

Frimley Business Park,

Frimley,

Camberley,

Surrey,

GU16 7SR.

United Kingdom

8. Marketing Authorisation Number(S)

PL 4416/0068

9. Date Of First Authorisation/Renewal Of The Authorisation

7 July 1988/7 July 1993

10. Date Of Revision Of The Text

11/2010

[1] NB This product is also known as Propanix 160-SR (for own label supply by Ashbourne Pharmaceuticals Ltd), Lopranol LA (for own label supply by Opus Pharmaceuticals only), Probeta LA (for own label supply by Trinity Pharmaceuticals Ltd only) and Rapranol (Propranolol Hydrochloride) SR 160mg Capsules (supplied by Ranbaxy (UK) Ltd. Only the relevant product name will be used throughout.

[2] Only marketed pack sizes will be shown.

* trade mark