Drug Class Description
Non-cardioselective b-blockers (beta-blockers).

Generic Name
Propranolol - angina

Drug Description
Propranolol hydrochloride Ph Eur 160 mg

Presentation
Pink/lavender prolonged release capsules, marked Inderal LA in white

Indications
a) Control of hypertension b) Management of anginac) Prophylaxis of migraine d) Management of essential tremore) Management of anxietyf) Adjunctive management of thyrotoxicosisg) Prophylaxis of upper gastro-intestinal bleeding in patients with portal hypertension and oesophageal varices

Adult Dosage
For oral administration.AdultsHypertension: The usual starting dose is one 160 mg Inderal LA capsule daily, taken either morning or evening. An adequate response is seen in most patients at this dosage. If necessary, it can be increased in 80 mg Half-Inderal LA increments until an adequate response is achieved. A further reduction in blood pressure can be obtained if a diuretic or other antihypertensive agent is given in addition to Inderal LA and Half-Inderal LA.Angina, anxiety, essential tremor, thyrotoxicosis and the prophylaxis of migraine: One Half-Inderal LA capsule daily, taken either morning or evening, may be sufficient to provide adequate control in many patients. If necessary the dose may be increased to one Inderal LA capsule per day and an additional Half-Inderal LA increment may be given.Portal hypertension: Dosage should be titrated to achieve approximately 25% reduction in resting heart rate. Dosing should begin with one 80 mg Half-Inderal LA capsule daily, increasing to one 160 mg Inderal LA capsule daily depending on heart rate response. Further 80 mg Half-Inderal LA increments may be added up to a maximum dose of 320 mg once daily.Patients who are already established on equivalent daily doses of Inderal tablets should be transferred to the equivalent doses of Half-Inderal LA or Inderal LA daily, taken either morning or evening.

Child Dosage
Inderal LA and Half-Inderal LA are not intended for use in children.

Elderly Dosage
Evidence concerning the relation between blood level and age is conflicting. It is suggested that treatment should start with one Half-Inderal LA capsule once daily. The dose may be increased to one Inderal LA capsule daily or higher as appropriate.

Contra Indications
Inderal LA and Half-Inderal LA must not be used if there is a history of bronchial asthma or bronchospasm. The product label states the following warning: “Do not take Inderal LA 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.Inderal LA and Half-Inderal LA, as with other beta-adrenoceptor blocking drugs, 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.Inderal LA and Half-Inderal LA must not be used in patients prone to hypoglycaemia, i.e., patients after prolonged fasting or patients with restricted counter-regulatory reserves.

Special Precautions
Inderal LA and Half-Inderal LA as with other beta-adrenoceptor blocking drugs:• although contra-indicated in uncontrolled heart failure may be used in patients whose signs of heart failure have been controlled. Caution must be exercised in patients whose cardiac reserve is poor.• should not be used in combination with calcium channel blockers with negative inotropic effects (e.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.• should not be used in patients with Prinzmetal's angina and beta-1 selective agents should be used with care.• although contra-indicated in severe peripheral arterial circulatory disturbances 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). Inderal LA and Half-Inderal LA occasionally causes hypoglycaemia, even 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. Severe hypoglycaemia associated with Inderal LA and Half-Inderal LA has rarely presented with seizures and/or coma in isolated patients. Caution must be exercised in the concurrent use of Inderal LA and Half-Inderal LA and hypoglycaemic therapy in diabetic patients. Inderal LA and Half-Inderal LA may prolong the hypoglycaemic response to insulin.• 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.• should be used to treat the elderly with caution starting with a lower dose.• will reduce heart rate as a result of its pharmacological action. In the rare instances when a treated patient develops symptoms that 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. An equivalent dosage of another beta-blocker may be substituted during the withdrawal period to facilitate a reduction in dosage below Inderal LA 80mg. Patients should be followed during withdrawal especially those with ischaemic heart disease.When a patient is scheduled for surgery and a decision is made to discontinue beta-blocker therapy, this should be done at least 24 hours prior to the procedure.The risk/benefit of stopping beta blockade should be made for each patient.Since the half-life may be increased in patients with significant hepatic or renal impairment, caution must be exercised when starting treatment and selecting the initial dose.Inderal LA and Half-Inderal LA must be used with caution in patients with decompensated cirrhosis.In patients with portal hypertension, liver function may deteriorate and hepatic encephalopathy may develop. There have been reports suggesting that treatment with propranolol may increase the risk of developing hepatic encephalopathy.Interference with laboratory tests: Inderal LA and Half-Inderal LA have been reported to interfere with the estimation of serum bilirubin by the diazo method and with the determination of catecholamines by methods using fluorescence.

Interactions
Inderal LA and Half-Inderal LA modify the tachycardia of hypoglycaemia. Caution must be exercised in the concurrent use of Inderal LA or Half-Inderal LA and hypoglycaemic therapy in diabetic patients. Propranolol may prolong the hypoglycaemic response to insulin.Caution must be exercised when prescribing a beta-adrenoceptor blocking drug with Class 1 antiarrhythmic agents such as disopyramide.Digitalis glycosides, in association with beta-adrenoceptor blocking drugs, may increase atrio-ventricular conduction time.Combined use of beta-adrenoceptor blocking drugs and calcium channel blockers with negative inotropic effects eg, verapamil, diltiazem, can lead to an exaggeration of these effects, particularly in patients with impaired ventricular function and/or sino-atrial or atrio-ventricular conduction abnormalities. This may result in severe hypotension, bradycardia and cardiac failure. Neither the beta-adrenoceptor blocking drug nor the calcium channel blocker should be administered intravenously within 48 hours of discontinuing the other.Concomitant therapy with dihydropyridine calcium channel blockers eg, nifedipine, may increase the risk of hypotension, and cardiac failure may occur in patients with latent cardiac insufficiency.Concomitant use of sympathomimetic agents, eg, adrenaline, may counteract the effect of beta-adrenoceptor blocking drugs. Caution must be exercised in the parenteral administration of preparations containing adrenaline to patients taking beta-adrenoceptor blocking drugs as, in rare cases, vasoconstriction, hypertension and bradycardia may result.Administration of propranolol during infusion of lignocaine may increase the plasma concentration of lignocaine by approximately 30%. Patients already receiving propranolol tend to have higher lignocaine levels than controls. The combination should be avoided.Concomitant use of cimetidine will increase, whereas concomitant use of alcohol will decrease, the plasma levels of propranolol.Beta-adrenoceptor blocking drugs may exacerbate the rebound hypertension, which can follow the withdrawal of clonidine. If the two drugs are co-administered, the beta-adrenoceptor blocking drug should be withdrawn several days before discontinuing clonidine. If replacing clonidine by beta-adrenoceptor blocking drug therapy, the introduction of beta-adrenoceptor blocking drugs should be delayed for several days after clonidine administration has stopped.Caution must be exercised if ergotamine, dihydroergotamine or related compounds are given in combination with propranolol since vasospastic reactions have been reported in a few patients.Concomitant use of prostaglandin synthetase inhibiting drugs, eg, ibuprofen or indomethacin, may decrease the hypotensive effects of propranolol.Concomitant administration of propranolol and chlorpromazine may result in an increase in plasma levels of both drugs. This may lead to an enhanced antipsychotic effect for chlorpromazine and an increased antihypertensive effect for propranolol.Caution must be exercised when using anaesthetic agents with Inderal LA and Half-Inderal LA. The anaesthetist should be informed and the choice of anaesthetic should be the agent with as little negative inotropic activity as possible. Use of beta-adrenoceptor blocking drugs with anaesthetic drugs may result in attenuation of the reflex tachycardia and increase the risk of hypotension. Anaesthetic agents causing myocardial depression are best avoided.Pharmacokinetic studies have shown that the following agents may interact with propranolol due to effects on enzyme systems in the liver which metabolise propranolol and these agents: quinidine, propafenone, rifampicin, theophylline, warfarin, thioridazine and dihydropyridine calcium channel blockers such as nifedipine, nisoldipine, nicardipine, isradipine and lacidipine. Owing to the fact that blood concentrations of either agent may be affected, dosage adjustments may be needed according to clinical judgement. (See also the interaction above concerning concomitant therapy with dihydropyridine calcium channel blockers).

Adverse Reactions
Inderal LA and Half-Inderal LA are 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. Cardiovascular: bradycardia, heart failure deterioration, postural hypotension which may be associated with syncope, cold cyanotic extremities. In susceptible patients: precipitation of heart block, exacerbation of intermittent claudication, Raynaud's phenomenon.CNS:confusion, dizziness, mood changes, nightmares, psychoses and hallucinations, sleep disturbances.Endocrine: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.Gastrointestinal:gastrointestinal disturbance.Haematological:purpura, thrombocytopenia.Integumentary:alopecia, dry eyes, psoriasiform skin reactions, exacerbation of psoriasis, skin rashes.Neurological:paraesthesia.Respiratory:bronchospasm may occur in patients with bronchial asthma or a history of asthmatic complaints, sometimes with fatal outcome.Special senses: visual disturbances.Others:fatigue and/or lassitude (often transient), an increase in ANA (antinuclear antibodies) has been observed, however the clinical relevance of this is not clear; isolated reports of myasthenia gravis like syndrome or exacerbation of myasthenia gravis have been reported in patients administered propranolol.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. Cessation of therapy with a beta-adrenoceptor blocking drug should be gradual. In the rare event of intolerance manifested as bradycardia and hypotension, the drug should be withdrawn and, if necessary, treatment for overdosage instituted.

Manufacturer
AstraZeneca

Drug Availability
(POM)

Updated
24 June 2009