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Propranolol hydrochloride in:
Propranolol hydrochloride is a synthetic beta-adrenergic receptor blocking agent which reduces cardiac activity by diminishing or preventing sympathetic beta-adrenoceptor stimulation.
It reduces the rate and force of contraction of the heart and decreases the rate of conduction of impulses through the conducting system. It has weak membrane-stabilising properties and does not possess intrinsic sympathomimetic activity. Propranolol is classified as non-cardioselective.
Propranolol is almost completely absorbed from the gastrointestinal tract, but is subject to considerable hepatic tissue binding and first pass metabolism. Peak plasma concentrations occur about 1 to 2 hours after a dose, but vary greatly between individuals.
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 (4-hydroxypropranolol) is considered to be biologically active but the contribution of metabolites to its overall activity is uncertain.
The biological half-life of propranolol is longer than would be anticipated from its plasma half-life of about 3-6 hours.
Propranolol crosses the placenta and traces are found in milk. It also crosses the blood-brain barrier. It is highly protein bound and reported not to be significantly dialysable.
Propranolol is indicated in the: control of essential and renal hypertension, management of angina pectoris, long term prophylaxis after recovery from acute myocardial infarction, control of most forms of cardiac dysrythmia, prophylaxis of migraine, management of essential tremor, control of anxiety and anxiety tachycardia, adjunctive management of thyrotoxicosis and thyrotoxic crisis, management of hypertropic obstructive cardiomyopathy, management of phaeochromocytoma (with an alpha blocker).
Adults
Oral dosage
Hypertension: a starting dose of 80mg twice a day may be increased at weekly intervals according to response. The usual dose range is 160-320mg per day. With concurrent diuretic or other anti-hypertensive agents a further reduction of blood pressure is obtained.
Angina, Anxiety, 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 anxiety, migraine and essential tremor is usually seen in the range 80-160mg/day and in angina in the range 120-240mg/day.
Dysrythmias, Anxiety Tachycardia, Hyper-trophic Obstructive Cardiomyopathy and Thyro-toxicosis: a dosage range of 10-40mg 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.
Phaeochromocytoma: (used only with an alpha-receptor blocking agent)
Pre-operative: 60mg daily for three days is recommended.
Non-operable malignant cases: 30mg daily.
Children
Oral dosage
Dysrythmias, Phaeochromocytoma, Thyrotoxicosis: dosage should be individually determined and the following is only a guide.
0.25-0.5mg/kg three or four times daily as required.
Migraine:
Under age of 12: 20mg two or three times daily.
Over age of 12: The adult dose.
Angilol LA Dosage:
Oral, once daily
Adults
Hypertension: the starting dose is one capsule daily, taken either morning or evening. An adequate response is seen in most patients at this dosage. If necessary, it can be increased to two capsules and a further reduction in BP can be attained if a diuretic or other antihypertensive agent is given in addition to ANGILOL LA.
Propranolol may mask the symptoms of hyperthyroidism. It may also mask the symptoms of hypoglycaemia, as well as enhancing the effects of hypoglycaemic agents in patients with diabetes mellitus.
Great care should be exercised in giving propranolol to patients undergoing anaesthesia and myocardial depressants such as halothane, cyclopropane, or ether should be avoided.
Special care should be taken with patients whose cardiac reserve is poor. Beta-adrenoceptor blocking agents should be avoided in overt heart failure.
However, they may be used in patients whose signs of failure have been controlled. Heart failure due to thyrotoxicosis often responds to propranolol alone, but if other adverse effects co-exist myocardial contractility must be maintained and signs of failure controlled with digitalis and diuretics.
In patients suffering from ischaemic heart disease, as with other beta-blocking agents, treatment should not be discontinued abruptly. Either the equivalent dosage of another beta-blocker may be substituted or the withdrawal of ANGILOL should be gradual.
Caution should be exercised when transferring patients from clonidine to beta-adrenoceptor blocking agents. If beta-adrenoceptor blocking agents and clonidine are given concurrently, clonidine should not be discontinued until several days after withdrawal of the beta-adrenoceptor blocking agent.
Care should be taken in prescribing a beta-adrenoceptor blocking agent with Class 1 antidysrhythmic agents such as disopyramide. Beta-adrenoceptor blocking agents should be used with caution in combination with verapamil in patients with impaired ventricular function. The combination should not be given to patients with conduction abnormalities.
Long term studies in animals have been conducted to evaluate toxic effects and carcinogenic potential. In 18-month studies, in both rats and mice, employing doses up to 150mg/kg/day, there was no evidence of significant medicine-induced toxicity. There were no medicine-related tumorigenic effects at any of the dosage levels.
Reproductive studies in animals did not show any impairment of fertility that was attributable to the medicine.
Use in pregnancy: propranolol hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
Use in breast-feeding mothers: propranolol hydrochloride is excreted in human milk. Caution should be exercised when ANGILOL is administered to a nursing woman.
Most adverse effects have been mild and transient and have rarely required the withdrawal of therapy.
Cardiovascular: bradycardia, congestive heart failure, intensification of AV block, hypotension, paraesthesia of hands, thrombocytopenic purpura, arterial insufficiency, usually of the Raynaud type.
Central Nervous System: lightheadedness, mental depression manifested by insomnia, lassitude, weakness, fatigue, reversible mental depression progressing to catatonia, visual disturbances, hallucinations, vivid dreams, an acute reversible syndrome characterised by disorientation for time and place, short term memory loss, emotional lability, slightly clouded sensorium and decreased performance on neuropsychometrics.
Gastrointestinal: nausea, vomiting, epigastric distress, abdominal cramping, diarrhoea, constipation, mesenteric arterial thrombosis, ischaemic colitis.
Allergic: pharyngitis and agranulocytosis, non-thrombocytopenic purpura, thrombocytopenic purpura.
Auto-immune: in extremely rare instances, systemic lupus erythematosus has been reported.
Miscellaneous: alopecia, LE-like reactions, psoriasiform rashes, dry eyes, male impotence, and Peyronie's disease have been reported.
The effects of other myocardial depressant agents, including anti-arrhythmics such as quinidine, procainamide, or lignocaine, phenytoin, and agents, which interfere with calcium transport, such as verapamil, may be enhanced by propranolol.
The effects of propranolol are diminished by beta-adrenoceptor stimulating agents such as isoprenaline. The hypotensive effects of propranolol may be dangerously reversed and the peripheral vasoconstrictor effects enhanced by alpha-adrenoceptor stimulating agents such as noradrenaline or those with mixed alpha- and beta-adrenoceptor stimulating properties such as adrenaline; bradycardia may also occur.
The effects of propranolol may be enhanced by adrenergic neurone blocking agents such as guanethidine or bethanidine, or catecholamine depleting agents such as reserpine, and the hypotensive effects by diuretics.
Propranolol may enhance some of the cardiac effects of digitalis and diminish others. It has been suggested that clonidine withdrawal symptoms may be exacerbated in patients who are concurrently taking a beta blocker.
Aluminium hydroxide gel greatly reduced intestinal absorption of propranolol.
Ethanol slows the rate of absorption of propranolol.
Phenytoin, phenobarbitone and rifampicin accelerate propranolol clearance.
Chlorpromazine, when used concomitantly with propranolol, results in increased plasma levels of both medicines.
Antipyrine and lidocaine have reduced clearance when used concomitantly with propranolol.
Thyroxine may result in a lower than expected T3 concentration when used concomitantly with propranolol.
Cimetidine decreases the hepatic metabolism of propranolol, delaying elimination and increasing blood levels.
Theophylline clearance is reduced when used concomitantly with propranolol.
Following recent overdosage, the stomach should be emptied by gastric lavage. Severe bradycardia and hypotension may respond to atropine 1 to 2mg or more intravenously. When response is inadequate the treatment of choice is high-dose glucagon, initially as a bolus dose of 5 to 10mg followed, if necessary, by an intravenous infusion of 1 to 5mg per hour or more according to response; the rate of infusion should be reduced as the patient improves.
Dobutamine or isoprenaline have also been used in the management of hypotension, large doses of the latter may be required to overcome competitive blockade of beta-adrenoceptors. Intravenous aminophylline, or inhaled or intravenous salbutamol, may be of benefit where bronchospasm occurs.
ANGILOL tablets and ANGILOL LA capsules should be stored at room temperature, protected from light and moisture.
Prescription medicine.
10mg and 40mg tablet: 100s and 500s.
160mg tablet: 50s.
160mg sustained-release capsule: 100s.
Propranolol hydrochloride is 1-isopropyl amino-3-(1-naphthyloxy)propan-2-ol hydrochloride. Its molecular formula and weight are C16H21NO2.HCl and 295.8 respectively.
Other ingredients of the tablets are: Lactose, Gelatine, Calcium carboxymethylcellulose, Magnesium stearate, Silicon dioxide, Opadry pink OY-1315 and Hydroxypropylmethyl cellulose.
Other ingredients of the sustained release capsules are: Sucrose, Maize starch, Polyvinylpyrrolidinone, Diffucril and Talc. The components of the capsule are: Erythrosine, Indigotine, Titanium dioxide and Gelatine.
Douglas Pharmaceuticals Ltd
PO Box 45-027
AUCKLAND 8
Ph: (09) 835-0660
Fax: (09) 835-0665
28 January 1999