PROPRANOLOL HYDROCHLORIDE

Posology Adults Hypertension A starting dose of 80mg twice a day may be increased at weekly intervals according to response. The usual dose range is 160 to 320mg per day. With concurrent diuretic or other antihypertensive drugs a further reduction of blood pressure is obtained.

Angina, migraine and essential tremor A starting dose of 40mg two or three times daily may be increased by the same amount at weekly intervals according to patient response. An adequate response in migraine and essential tremor is usually seen in the range 80 to 160mg/day and in angina in the range 120 to 240mg/day.

Situational and generalised anxiety A dose of 40mg daily may provide short term relief of acute situational anxiety. Generalised anxiety, requiring longer term therapy, usually responds adequately to 40mg twice daily which, in individual cases, may be increased to 40mg three times daily.

Treatment should be continued according to response. Patients should be reviewed after 6 to 12 months treatment. Arrhythmias, anxiety tachycardia, hypertrophic obstructive cardiomyopathy and thyrotoxicosis A dosage range of 10 to 40mg three or four times a day usually achieves the required response.

Post myocardial infarction Treatment should start between days 5 and 21 after myocardial infarction, with an initial dose of 40mg four times a day for 2 or 3 days. In order to improve compliance the total daily dosage may thereafter be given as 80mg twice a day.

Portal hypertension Dosage should be titrated to achieve approximately 25% reduction in resting heart rate. Dosage should begin with 40mg twice daily, increasing to 80mg twice daily depending on heart rate response. If necessary, the dose may be increased incrementally to a maximum of 160mg twice daily.

Phaeochromocytoma (Used only with an alpha-receptor blocking drug). Pre-operative: 60 mg daily for 3 days is recommended. Non-operable malignant cases: 30 mg daily. Older people Evidence concerning the relation between blood level and age is conflicting.

Propranolol hydrochloride should be used to treat older people with caution. It is suggested that treatment should start with the lowest dose. The optimum dose should be individually determined according to clinical response. 5 mg/kg three or four times daily as required.

Propranolol hydrochloride is usually well tolerated. In clinical studies the undesired events reported are usually attributable to the pharmacological actions of propranolol. The following undesired events, listed by body system, have been reported.

The following definitions of frequencies are used:

Very common (≥1/10), common (≥/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). System Organ class Frequency Undesirable Effect Blood and lymphatic system disorders Rare Thrombocytopaenia Endocrine disorders Not known Hypoglycaemia in neonates, infants, children, elderly patients, patients on haemodialysis, patients on concomitant antidiabetic therapy, patients with prolonged fasting and patients with chronic liver disease has been reported, seizure linked to hypoglycaemia Nervous system disorders Common Sleep disturbances, nightmares Rare Hallucinations, psychoses, mood changes, confusion, memory loss, paraesthesia Very rare Isolated reports of myasthenia gravis like syndrome or exacerbation of myasthenia gravis have been reported Eye disorders Rare Dry eyes, visual disturbances Cardiovascular disorders Common Bradycardia, cold extremities, Raynaud’s phenomenon Rare Heart failure deterioration, precipitation of heart block, postural hypotension, which may be associated with syncope, exacerbation of intermittent claudication Respiratory, thoracic and mediastinal disorders Rare Bronchospasm may occur in patients with bronchial asthma or a history of asthmatic complaints, sometimes with fatal outcome Gastrointestinal disorders Uncommon Gastrointestinal disturbance, such as nausea, vomiting, diarrhoea Skin and subcutaneous tissue disorders Rare Purpura, alopecia, psoriasiform skin reactions, exacerbation of psoriasis, skin rashes General disorders and administration site conditions Common Fatigue and/or lassitude (often transient) Rare Dizziness Investigations Very rare An increase in ANA (Antinuclear Antibodies) has been observed, however the clinical relevance of this is not clear Discontinuance of the drug should be considered if, according to clinical judgement, the well-being of the patient is adversely affected by any of the above reactions.

3), may be used in patients whose signs of heart failure have been controlled. Caution must be exercised in patients whose cardiac reserve is poor. g. verapamil, diltiazem), as it can lead to an exaggeration of these effects particularly in patients with impaired ventricular function and/or SA or AV conduction abnormalities.

This may result in severe hypotension, bradycardia and cardiac failure. Neither the beta-blocker nor the calcium channel blocker should be administered intravenously within 48 hours of discontinuing the other. 3), may also aggravate less severe peripheral arterial circulatory disturbances.

• due to its negative effect on conduction time, caution must be exercised if it is given to patients with first degree heart block. • may block/modify the signs and symptoms of the hypoglycaemia (especially tachycardia). g. neonates, infants, children, elderly patients, patients on haemodialysis or patients suffering from chronic liver disease and patients suffering from overdose.

Severe hypoglycaemia associated with Propranolol hydrochloride has rarely presented with seizures and/or coma in isolated patients. Caution must be exercised in the concurrent use of Propranolol hydrochloride and hypoglycaemic therapy in diabetic patients.

3). • may mask the signs of thyrotoxicosis. • should not be used in untreated phaeochromocytoma. However, in patients with phaeochromocytoma, an alpha-blocker may be given concomitantly. • will reduce heart rate as a result of its pharmacological action.

In the rare instances when a treated patient develops symptoms which may be attributable to a slow heart rate, the dose may be reduced. • may cause a more severe reaction to a variety of allergens when given to patients with a history of anaphylactic reaction to such allergens.

Such patients may be unresponsive to the usual doses of adrenaline used to treat the allergic reactions. Abrupt withdrawal of beta-blockers is to be avoided. The dosage should be withdrawn gradually over a period of 7 to 14 days. Patients should be followed during withdrawal especially those with ischaemic heart disease.

1. Propranolol hydrochloride must not be used if there is a history of bronchial asthma or bronchospasm. The product label states the following warning: “Do not take Propranolol hydrochloride if you have a history of asthma or wheezing”.

A similar warning appears in the patient information leaflet. Bronchospasm can usually be reversed by beta2 agonist bronchodilators such as salbutamol. Large doses of the beta2 agonist bronchodilator may be required to overcome the beta blockade produced by propranolol and the dose should be titrated according to the clinical response; both intravenous and inhalational administration should be considered.

The use of intravenous aminophylline and/or the use of ipratropium (given by nebuliser) may also be considered. Glucagon (1 to 2 mg given intravenously) has also been reported to produce a bronchodilator effect in asthmatic patients.

Oxygen or artificial ventilation may be required in severe cases. Propranolol hydrochloride as with other beta-blockers must not be used in patients with any of the following conditions: known hypersensitivity to the substance; bradycardia; cardiogenic shock; hypotension; metabolic acidosis; after prolonged fasting; severe peripheral arterial circulatory disturbances; second or third degree heart block; sick sinus syndrome; untreated phaeochromocytoma; uncontrolled heart failure or Prinzmetal’s angina.

, patients after prolonged fasting or patients with restricted counter-regulatory reserves. Patients with restricted counter regulatory reserves may have reduced autonomic and hormonal responses to hypoglycaemia which includes glycogenolysis, gluconeogenesis and /or impaired modulation of insulin secretion.

Patients at risk for an inadequate response to hypoglycaemia includes individuals with malnutrition, prolonged fasting, starvation, chronic liver disease, diabetes and concomitant use of drugs which block the full response to catecholamines.