This information is intended for use by health professionals
Excipient with known effect:Sodium metabisulphite For the full list of excipients, see section 6.1.
Severe hypersensitivity reactions, anaphylactic shockIM Injection:Adults: The usual dose is 500 micrograms (0.5ml of adrenaline 1/1000). If necessary, this dose may be repeated several times at 5-minute intervals according to blood pressure, pulse and respiratory function.Half doses of adrenaline may be safer for patients who are taking amitriptyline, imipramine or a beta blocker.
Paediatric populationThe following doses of adrenaline 1/1,000 are recommended:
|Over 12 years||0.5 mg IM (0.5ml 1:1000 solution)|
|6 - 12 years||0.3 mg IM (0.3ml 1:1000 solution)|
|6 months - 6 years||0.15 mg IM (0.15ml 1:1000 solution)|
|Under 6 months||0.01mg/kg IM (0.01ml/kg 1:1000 solution)|
The dosage is the same as for younger adults but particular caution is required when administering adrenaline to elderly patients (see section 4.4).
Adrenaline should be used with caution in patients with severe renal impairment (see section 4.4).
Method of AdministrationAdrenaline Injection BP. 1/1000 (1mg/ml) may be administered undiluted by S.C. or IM injection. In the shocked patient, the intramuscular route is recommended as absorption from the intramuscular site is more rapid and reliable than from the subcutaneous site. A small volume syringe should be used.
Sympathomimetic agents/Oxytocin:Adrenaline should not be administered concomitantly with oxytocin or 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. (See section 4.9).
Beta-adrenergic blocking agents:Severe hypertension and reflex bradycardia may occur with non-selective beta-blocking drugs 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 (See section 4.4).
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.
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. 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.
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.
PregnancyAdrenaline crosses the placenta. There is some evidence of a slightly increased incidence of congenital abnormalities.Injection of adrenaline may cause anoxia, foetal tachycardia, cardiac irregularities, extra systoles and louder heart sounds.Adrenaline usually inhibits spontaneous or oxytocin induced contractions of the pregnant human uterus and may delay the second stage of labour. In dosage sufficient to reduce uterine contractions, the drug may cause a prolonged period of uterine atony with haemorrhage.Parenteral Adrenaline should not be used during the second stage of labour.
Breast-feedingAdrenaline is distributed into breast milk. Breast-feeding should be avoided in mothers receiving Adrenaline injection. Adrenaline should not be used in pregnancy unless clearly necessary.
Frequencies are defined using the following convention: not known (cannot be estimated from the available data).
|System organ class||Frequency||Undesirable effects|
|Immune system disorders||Not Known||Anaphylaxis, possibly with severe bronchospasm (See section 4.4).|
|Metabolism and nutrition disorders||Not Known||Hypokalaemia, metabolic acidosis (see section 4.4). Inhibition of insulin secretion and hyperglycaemia even with low doses, gluconeogenesis, glycolysis, lipolysis and ketogenesis.|
|Psychiatric disorders||Not Known||Psychotic states, Anxiety, fear, confusion, irritability, insomnia|
|Nervous system disorders||Not Known||Headache, dizziness, tremors, restlessness 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||Not Known|| 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. (See section 4.5)
Stress cardiomyopathy (such as Takotsubo syndrome)Adrenaline causes E.C.G. changes including a decrease in T-Wave amplitude in all leads in normal subjects.
|Vascular disorders||Not Known||Hypertension (with risk of cerebral haemorrhage). Coldness of extremities may occur even with small doses of Adrenaline.|
|Respiratory, thoracic and mediastinal disorders||Not Known||Dyspnoea, Pulmonary oedema may occur after excessive doses or in extreme sensitivity.|
|Gastrointestinal disorders||Not Known||Dry mouth, Reduced appetite, nausea, vomiting, hypersalivation.|
|Renal and urinary disorders||Not Known||Difficulty in micturition, urinary retention.|
|General disorders and administration site conditions||Not Known||Sweating, weakness. Repeated injections of Adrenaline can cause local ischaemic necrosis as a result of vascular constriction at the injection site. Tissue necrosis may also occur in the extremities, kidneys and liver.|
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
SymptomsAfter overdosage or inadvertent intravenous administration of usual intramuscular subcutaneous doses of Adrenaline, systolic and diastolic blood pressure rise sharply; venous pressure also rises. Cerebrovascular or other haemorrhages and hemiplegia may result, especially in elderly patients. Pulmonary oedema may occur. Adrenaline overdosage causes transient bradycardia followed by tachycardia and may cause other potentially fatal cardiac arrhythmias. Kidney failure, metabolic acidosis and cold white skin may also occur.
TreatmentBecause Adrenaline is rapidly inactivated in the body, treatment of acute toxicity is mainly supportive. The pressor effects of Adrenaline may be counteracted by an immediate intravenous injection of a quick-acting alpha-adrenoreceptor blocking agent, such as 5-10mg of phentolamine mesylate, followed by a beta-adrenoreceptor blocking agent, such as 2.5 - 5mg of propranolol. Arrhythmias, if they occur, may be counteracted by propranolol injection.
AbsorptionAdrenaline has a rapid onset of action after intramuscular administration and in the shocked patient its absorption from the intramuscular site is faster and more reliable than from the subcutaneous site. The plasma half-life is about 2-3 minutes. However, when given by subcutaneous or intramuscular injection, local vasoconstriction may delay absorption so that the effects may last longer than the half-life suggests.
BiotransformationAdrenaline is rapidly inactivated in the body, mostly in the liver by the enzymes catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO).
EliminationMuch of a dose of adrenaline is excreted as metabolites in urine.