SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

ANGILOL/Propranolol 80mg

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Propranolol HCl BP 80.00mg

3    PHARMACEUTICAL FORM

Film-coated tablet

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Indicated in the management of angina. Control of essential and renal hypertension. Control of essential tremor. Control of anxiety, and anxiety tachycardia. Control of most forms of cardiac dysrhythmias. Management of hypertrophic obstructive cardiomyopathy.    Management of

phaeochromocytoma. An adjunct in the management of thyrotoxicosis and thyrotoxic crises.

4.2    Posology and method of administration

In hypertension, the starting dose of ANGILOL should be 80mg twice a day, to be increased by the same amount at weekly intervals, according to patient response. Usually a response is seen within the dose range 160 - 320mg per day. A further reduction of blood pressure may be achieved when a diuretic and/or anti-hypertensive therapy is given in addition to ANGILOL.

In angina, anxiety and essential tremor, the starting dose is 40mg two or three times dally, increasing by the same amount at weekly intervals, according to patient response.

An adequate response in anxiety and essential tremor is usually seen in the range of 80 - l60mg daily in divided doses. In angina the dose to achieve adequate response will usually be l20 - 240mg/day (in divided doses).

In cardiac dysrhythmias, anxiety tachycardia, hypertrophic obstructive cardiomyopathy and thyrotoxicosis, most patients respond within the dosage range of 10 - 40mg three or four times a day.

In phaeochromocytoma (used only in conjunction with an alpha-receiver blocking drug) pre-operatively: 60mg daily for three days is recommended -malignant cases (non-operable): 30mg daily.

Children:

Cardiac dysrhythmias, phaeochromocytoma, thyrotoxicosis: the dose of ANGILOL should be determined according to the cardiac status of the patient and the circumstances necessitating treatment. The doses given are intended only as a guide:

Oral: 0.25 - 0.5mg/kg three or four times daily as required.

Fallot's Tetralogy: The value of ANGILOL in this condition is confined mainly to the relief of the right-ventricular outflow tract shut-down. It is also useful for treatment of associated dysrhythmias and angina. Dosage should be individually determined according to circumstances and is usually up to l mg/kg repeated three or four times daily as required.

Elderly:

The optimum dose should be individually determined according to the clinical response.

Route of administration: Oral

4.3 Contraindications

1. Hypersensitivity to Propanonol

2.    In the presence of 2nd and 3rd degree heart block

3.    Sick Sinus syndrome

4.    Bradycardia

5.    Untreated phaeochromocytoma

6.    Uncontrolled heart failure

7.    Asthma, heart failure, intermittent claudication

8.    Severe peripheral circulatory disturbances

9.    Prinzmetals angina

10.    If there is a history of bronchospasm

11.    After prolonged fasting

12.    In metabolic acidosis (e.g. in diabetes)

The text on the label for this product will carry this following warning. ’Do not use if you have a history of wheezing or asthma.

4.4 Special warnings and precautions for use

Angilol should be given with caution to patients with liver and renal insufficiency.

Angilol should be given with caution to patients with peripheral circulatory disturbances.

Special care should he taken with patients whose cardiac reserve is poor. Heart failure due to thyrotoxicosis often responds to ANGILOL alone, but if other adverse factors co-exist myocardial contractility must be maintained and signs of failure controlled with digitalis and diuretics.

It is important that treatment with a beta-blocking agent is not discontinued abruptly. Either the equivalent dosage of another beta-blocker may be substituted or the withdrawal of ANGILOL should be gradual.

Anaesthesia: ANGILOL can cause an altered response to stress and therefore it may be necessary to withdraw the drug before surgery. If it is decided to withdraw ANGILOL it should be done 24 hours before elective surgery.

In emergency, or when interruption of treatment might expose the patient to severe uncontrolled angina or dysrhythmia, such withdrawal may be impracticable.

Anaesthesia may still proceed, however, provided that the patient is protected against vagal dominance by the intravenous administration of atropine l - 2mg and that agents such as ether, chloroform, cyclopropane and trichloroethylene are avoided.

Beta-blockers may induce bradycardia-reduction in dose may be necessary. Patients with liver and renal insufficiency.

Patients with psoriasis should take beta-blockers only after careful consideration.

Beta-blockers may increase both the sensitivity towards allergens and the seriousness of anaphylactic reactions.

Beta-blockers should only be given with caution to patients with first degree heart block.

4.5 Interaction with other medicinal products and other forms of interaction

Cimetidine increases plasma concentration of Propranolol. Rifampicin reduces plasma concentration of Propranolol. Propranolol interacts with verapamil the effect being asystole, hypotension and heart failure. Propranolol increases plasma concentration of chlorpromazine.

Interaction of beta-blocker therapy with the following drugs should be considered with the following risks:

•    Anaesthetics:- Enhanced hypotensive effect; increased risk of bupivacaine toxicity.

•    Anti-arrythmics:- Increased risk of lignocaine toxicity with propranolol.

•    Antidepressants:- Fluvoxamine increases plasma concentration of propranolol. Hypotensive effect enhanced with tricyclic antidepressants.

•    Ca++ channel antagonists:- Increased risk of bradycardia

•    Digitalis glycosides:- AV block and risk of bradycardia

•    Clonidine:- Enhanced hypotensive effect and increased risk of withdrawal hypertensive effect

•    Insulin and oral antidiabetic drugs:- Enhanced hypoglycemic effects and masking of warning signs such as tremor

•    Cimetidine:- Plasma concentration increased

•    Hydralazine:- Enhanced hypotensive effect of increased plasma levels of propanolol

•    Alcohol:- Decreased plasma levels of propanolol and enhanced hypotensive effect

•    Adrenaline :- Severe hypertension

•    Dihydropyridine derivatives:- Increased risk of bradycardia and AV block

•    Prostaglandin synthetase inhibiting drugs:- Hypotensive effect may be decreased

•    Tricyclic antidepressants:- Increased plasma concentration

•    Barbiturates and phenothiazines:- Enhanced hypotensive effect

•    Sympathomimetic agents and other anti-hypertension agents:- Severe hypertension.

4.6 Pregnancy and lactation

ANGILOL should not be given in pregnancy unless its use is essential. There is no evidence of teratogenicity with ANGILOL.

Beta-blockers reduce placental perfusion, which may result in intrauterine foetal death, immature deliveries. In addition, adverse effects (especially hypoglycemia and bradycardia) may occur in the foetus and neonate in the postnatal period.

Breast feeding is not recommended.

4.7 Effects on ability to drive and use machines

The side effect of bradycardia and hypotension may affect the ability to drive.

4.8 Undesirable effects

Cold extremities, nausea, insomnia, lassitude and diarrhoea are usually transient and can often be avoided by gradual reduction of treatment. Isolated cases of purpura, erythrematous rash and paraesthesia of the hands have been reported. In the rare event of intolerance of ANGILOL manifested by bradycardia and hypotension, the drug should be withdrawn and if necessary treatment instituted for overdosage.

The following undesirable effects may also he present:

•    A slowed AV-condition or increase of an existing AV-conduction, AV block, heart failure.

•    Hypotension.

•    CNS effects: confusion, impotence; dizziness, depression.

•    May mask the symptoms of thyrotoxicosis and hypoglycaemia.

•    An increase in (A)nti (N)uclear (A)ntibodies has been seen: its clinical relevance is not clear.

•    Side-effects of bronchospasm in suspectible individuals.

•    Dry eyes

Overdose

Excessive bradycardia can be countered with atropine 1 - 2mg intravenously followed if necessary by a beta-receptor stimulant such as isoprenaline 25mg intravenously or orciprenaline 0.5mg intravenously.

Symptoms of overdose include; bradycardia, hypotension, bronchospasm and acute cardiac insufficiency. After ingestion of an overdose or in the case of hypersensitivity the patient should be kept under close supervision and be treated in an intensive care ward. Absorption of any drug material still present in the gastrointestinal tract can be prevented by gastric lavage, administration of activated charcoal and a laxative. Treatment with glucagon may be considered. Administration of calcium ions, or the use of a cardiac pacemaker may also be considered. In patients intoxicated with hydrophilic betablocking agents haemodialysis or haemoperfusion may be considered.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

A white or off-white odourless powder with a bitter taste. M.P. about 164°C. It absorbs less than 1% of moisture at relative humidities of up to 80% at 25°C. Soluble 1 in 20 of water and alcohol; slightly soluble in chloroform; practically insoluble in ether. A 1% Solution in water has a pH of 5 to 6.

Propranolol is a competitive inhibitor of the effects of catecholamines at beta-adrenergic receptor sites. The Principal effect of beta-adrenoceptor blockade is to reduce cardiac activity by diminishing or Preventing beta-adrenoceptor stimulation.

Propanolol induces intrinsic sympathicomimetic activity, and exhibits negative inotropic effects.

Propanolol possesses membrane stabilising effects.

5.2 Pharmacokinetic properties

Propranolol is almost completely absorbed from the gastro-intestinal tract, but is subject to considerable first-pass metabolism. Peak plasma concentrations occur about 2 hours after a dose. It is metabolised in the liver, the metabolites being excreted in the urine together with only small amounts of unchanged Propranolol; at least one of its metabolites is considered to be biologically active. The biological half-life of Propanolol is longer than would be anticipated from its plasma half-life of about 3 to 6 hours. Propranolol crosses the placenta and traces are found in milk. It also crosses the blood-brain barrier, it is highly protein bound and not reported to be significantly dialysable.

5.3 Preclinical safety data

Not applicable.

6 PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Lactose Gelatin Stearic Acid Magnesium Stearate.

Ethylcellulose

Hydroxypropyimethylcellulose Diethylphthalate Opaspray K-1-5506 (solids) Beeswax.

6.2 Incompatibilities

None stated.

6.3 Shelf life

36 months

6.4 Special precautions for storage

Store below 25°C in a dry place. Keep containers securely closed.

6.5 Nature and contents of container

Opaque, high density polystyrene containers, with polythene lids, and/or polypropylene containers with polypropylene or polythene lids, and polyurethane foam sponge wads or polythene wads.

Pack sizes: 50, 100, 250, 500 and 1000 tablets.

250 micron PVC glass-clear/bluish rigid PVC (pharmaceutical grade). 25 micron hard-tempered aluminium foil coated on the dull side with 6 - 7 gsm heat seal lacquer and printed on the bright side.

Pack size: 28 tablets.

6.6 Special precautions for disposal

Not applicable

7 MARKETING AUTHORISATION HOLDER

Chelonia Healthcare Limited

Boumpoulinas 11, 3 ^rd Floor

NICOSIA

CYPRUS

PC. 1060

CYPRUS

8    MARKETING AUTHORISATION NUMBER(S)

PL 33414/0097

DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

31^st December 1980 / 26^th August 1998

DATE OF REVISION OF THE TEXT

05/12/2008

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