Sympathomimetics.

Generic - cardiovascular system

Each ml of solution for injection contains 1 mg of adrenaline (epinephrine) as the acid tartrate.

Sterile Injection.

Adrenaline Injection BP 1 in 1000 may be used in the treatment of acute allergy and anaphylactic shock.

Intramuscular injection of Adrenaline 1 in 1000 gives symptomatic relief in acute allergy and anaphylactic shock. Subcutaneous injection is not generally recommended.

Volume of Adrenaline injection 1 in 1000 for intramuscular or subcutaneous injection:

For children over 12 years of age who are small or prepubertal, a dose of 0.25 ml should be given.

These doses may be repeated several times if necessary at 5 minute intervals according to blood pressure, pulse & respiratory function.

There are no specific dosage regimes for Adrenaline injection in elderly patients. However, Adrenaline should be used with great caution in these patients, as they may be more susceptible to the cardiovascular side effects of Adrenaline.

Hypersensitivity to adrenaline, sodium metabisulphite or any of the other ingredients.

Adrenaline 1 in 1000 should not be used in fingers, toes, ears, nose or genitalia owing to the risk of ischaemic tissue necrosis.

Adrenaline should be used with caution in patients with hyperthyroidism, diabetes mellitus, phaeochromocytoma, narrow angle glaucoma, hypokalaemia, hypercalcaemia, severe renal impairment, prostatic adenoma leading to residual urine, cerebrovascular disease, organic brain damage or arteriosclerosis, in elderly patients, in patients with shock (other than anaphylactic shock) and in organic heart disease or cardiac dilatation (severe angina pectoris, obstructive cardiomyopathy, hypertension) as well as most patients with arrhythmias. Anginal pain may be induced when coronary insufficiency is present.

Adrenaline should be used cautiously, if at all, during general anaesthesia with halogenated hydrocarbon anaesthetics.

Adrenaline should not be used during the second stage of labour.

Accidental intravascular injection may result in cerebral haemorrhage due to the sudden rise in blood pressure.

Intramuscular injections of Adrenaline into the buttocks should be avoided because of the risk of tissue necrosis.

Prolonged use of Adrenaline can result in severe metabolic acidosis because of elevated blood concentrations of lactic acid.

Adrenaline Injection contains sodium metabisulphite, which can cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes, in certain susceptible individuals.

The presence of sodium metabisulphite in parenteral Adrenaline and the possibility of allergic-type reactions should not deter use of the drug when indicated for the treatment of serious allergic reactions or for other emergency situations.

Sympathomimetic agents:

Adrenaline should not be administered concomitantly with other sympathomimetic agents because of the possibility of additive effects and increased toxicity.

Alpha-adrenergic blocking agents:

Alpha-blockers such as phentolamine antagonise the vasoconstriction and hypertension effects of adrenaline. This effect may be beneficial in adrenaline overdose.

Beta-adrenergic blocking agents:

Severe hypertension and reflex bradycardia may occur with non-cardioselective beta-blocking agents such as propranolol, due to alpha-mediated vasoconstriction.

Beta-blockers, especially non-cardioselective agents, also antagonise the cardiac and bronchodilator effects of adrenaline. Patients with severe anaphylaxis who are taking non-cardioselective beta-blockers may not respond to adrenaline treatment.

General Anaesthetics:

Administration of Adrenaline in patients receiving halogenated hydrocarbon general anaesthetics that increase cardiac irritability and seem to sensitise the myocardium to Adrenaline may result in arrhythmias including ventricular premature contractions, tachycardia or fibrillation.

Antidepressant agents:

Tricyclic antidepressants such as imipramine inhibit reuptake of directly acting sympathomimetic agents, and may potentiate the effect of adrenaline, increasing the risk of development of hypertension and cardiac arrhythmias.

Although monoamine oxidase (MAO) is one of the enzymes responsible for Adrenaline metabolism, MAO inhibitors do not markedly potentiate the effects of Adrenaline.

Phenothiazines:

Phenothiazines block alpha-adrenergic receptors (see above).

Adrenaline should not be used to counteract circulatory collapse or hypotension caused by phenothiazines; a reversal of the pressor effects of Adrenaline may result in further lowering of blood pressure.

Antihypertensive agents:

Adrenaline specifically reverses the antihypertensive effects of adrenergic neurone blockers such as guanethidine, with the risk of severe hypertension. Adrenaline increases blood pressure and may antagonise the effects of antihypertensive drugs.

Other drugs:

Adrenaline should not be used in patients receiving high dosage of other drugs (e.g. cardiac glycosides) that can sensitise the heart to arrhythmias. Some antihistamines (e.g. diphenhydramine) and thyroid hormones may potentiate the effects of Adrenaline, especially on heart rhythm and rate.

Hypokalaemia:

The hypokalaemic effect of adrenaline may be potentiated by other drugs that cause potassium loss, including corticosteroids, potassium-depleting diuretics, aminophylline and theophylline.

Hyperglycaemia:

Adrenaline-induced hyperglycaemia may lead to loss of blood-sugar control in diabetic patients treated with insulin or oral hypoglycaemic agents.

The adverse events of adrenaline mainly relate to the stimulation of both alpha- and beta-adrenergic receptors. The occurrence of undesirable effects depends on the sensitivity of the individual patient and the dose involved.

Immune system disorders:

Anaphylaxis, possibly with severe bronchospasm

Metabolism and nutrition disorders:

Hyperglycaemia, hypokalaemia, metabolic acidosis

Psychiatric disorders:

Anxiety

Nervous system disorders

Headache, dizziness, tremors

In patients with Parkinsonian Syndrome, Adrenaline increases rigidity and tremor.

Subarachnoid haemorrhage and hemiplegia have resulted from hypertension, even following subcutaneous administration of usual doses of Adrenaline.

Cardiac disorders:

Disturbances of cardiac rhythm and rate may result in palpitation and tachycardia. Chest pain/angina may occur. Adrenaline can cause potentially fatal ventricular arrhythmias including fibrillation, especially in patients with organic heart disease or those receiving other drugs that sensitise the heart to arrhythmias.

Adrenaline causes E.C.G. changes including a decrease in T-Wave amplitude in all leads in normal subjects.

Vascular disorders:

Hypertension (with risk of cerebral haemorrhage).

Coldness of extremities may occur even with small doses of Adrenaline.

Respiratory disorders:

Pulmonary oedema may occur after excessive doses or in extreme sensitivity.

Gastrointestinal disorders:

Nausea, vomiting.

Renal and urinary disorders:

Difficulty in micturition, urinary retention.

General disorders and administrative site conditions:

Sweating, weakness.

Repeated injections of Adrenaline can cause necrosis as a result of vascular constriction at the injection site. Tissue necrosis may also occur in the extremities, kidneys and liver.

hameln pharmaceuticals ltd

(POM)

04 June 2009