Adrenaline Injection 1 In 10 000
SUMMARY OF PRODUCT CHARACTERISTICS 1 NAME OF THE MEDICINAL PRODUCT
Dilute Adrenaline/Epinephrine Injection 1:10,000 Adrenaline (Epinephrine) Injection 1 in 10,000
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Adrenaline (Epinephrine) as Acid Tartrate Ph Eur 0.01%w/v
3 PHARMACEUTICAL FORM
Solution for Injection.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Cardiopulmonary Resuscitation.
Acute Anaphylaxis when intramuscular route has been ineffective.
4.2 Posology and method of administration Cardiopulmonary Resuscitation.
Adults and children over 12 years
1 in 10,000 (100 micrograms/ml) is recommended in a dose of 10ml, by central intravenous injection.
If injected through a peripheral line, the drug must be flushed with at least 20ml Sodium Chloride 0.9% injection (to aid entry into the central circulation).
The procedure for Cardiopulmonary Resuscitation as given in the algorithm which reflects the recommendations of the European Resuscitation Council and the Resuscitation Council (UK) should be employed.
If venous access is not available, intraosseous route is recommended.
Children Under 12 years It is not recommended.
Elderly
It should be used with great caution in these patients who may be more susceptible to the cardiovascular side effects of adrenaline.
Acute life threatening allergic reactions
Acute Anaphylaxis
Constant vigilance is needed to ensure that the correct strength of Adrenaline solution is used in the treatment of anaphylaxis. Anaphylactic shock kits need to make a very clear distinction between the 1 in 10,000 strength and the 1 in 1000 strength Adrenaline solutions.
(The intramuscular route is the first choice route for administration of Adrenaline (1:1000) in the management of anaphylactic shock. It is also important that, where intramuscular injection might still succeed, time should not be wasted seeking intravenous access.)
Adults & Children over 12 years:
Where the patient is severely ill and there is real doubt about adequacy of the circulation and absorption from the intramuscular injection site, Adrenaline 1 in 10,000 may be given by slow intravenous injection.
In a dose of 500 micrograms ( 5ml of the dilute 1 in 10,000 adrenaline solution) given at a rate of 100 micrograms (1ml of the dilute 1 in 10,000 adrenaline solution) per minute, stopping when a response obtained.
Children under 12 years
Children can be given a dose of 10 micrograms/kg (0.lml of the dilute 1 in 10,000 adrenaline injection per kg) by slow intravenous injection over several minutes.
Elderly
It should be used with great caution in these patients who may be more susceptible to the cardiovascular effects of Adrenaline.
These should be regarded as relative and not absolute contraindications in life threatening emergency situations.
Adrenaline is contraindicated in patients with shock (other than anaphylactic shock), organic heart disease, or cardiac dilatation, as well as most patients with arrhythmias, organic brain damage, or cerebral arteriosclerosis.
Adrenaline injection is contraindicated in patients with narrow angle glaucoma. Adrenaline is contraindicated for use during general anaesthesia with chloroform, trichloroethylene, or cyclopropane, and should be used cautiously, it at all, with other halogenated hydrocarbon anaesthetics, adrenaline is contraindicated for use in fingers, toes, ears, nose or genitalia.
Adrenaline should not be used during the second stage of labour (see pregnancy and lactation).
4.4 Special warnings and precautions for use
IM injection 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 1 in 10,000 BP contains sodium metabisulphite that 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.
Extreme care is also needed in conditions which predispose a patient to adverse effects on the heart, such as hyperthyroidism.
Care should be exercised in patients who suffer from hypertension and Diabetes mellitus.
4.5 Interactions with other medicinal products and other forms of interaction
Sympathomimetic agents: Adrenaline should not be administered concomitantly with other sympathomimetic agents because of the possibility of additive effects and increased toxicity.
Alpha and beta blocking agents: The cardiac and bronchodilating effects of adrenaline are antagonised by P-adrenergic blocking drugs such as propranolol, and the vasoconstriction and hypertension caused by high doses
of adrenaline are antagonised by alpha-adrenergic blocking agents such as phentolamine. Because of their alpha-adrenergic blocking properties, ergot alkaloids can reverse the pressor response to adrenaline.
General anaesthetics (see contraindications)
Administration of adrenaline in patients receiving cyclopropane or 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.
Prophylactic administration of lignocaine or prophylactic administration of propranolol 0.05 mg/kg may protect against ventricular irritability if adrenaline is used during anaesthesia with a halogenated hydrocarbon anaesthetic.
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. Tricyclic antidepressants such as imipramine, some antihistamines (e.g. diphenhydramine) and thyroid hormones may potentiate the effects of adrenaline, especially on heart rhythm and rate. Although monoamine oxidase (MAO) is one of the enzymes responsible for adrenaline metabolism, MAO inhibitors do not markedly potentiate the effects of adrenaline therefore caution is still necessary.
Clonidine may increase the risk of hypertension.
Dopexamine may enhance the action of adrenaline.
Entacapone may enhance the action of adrenaline.
Antipsychotics antagonise the hypertensive effect of sympathomimetics. Doxapram: Increased risk of hypertension when sympathomimetics are given with doxapram.
Ergotamine and Methysergide: There is an increased risk of ergotism if sympathomimetics are given with these drugs.
Oxytocin: Concomitent use with adrenaline may increase the vasopressor effect and thus a risk of hypertension may develop. (see also Section 4.6)
Adrenaline should not be used to counteract circulatory collapse of hypotension caused by phenothiazines: a reversal of adrenaline’s pressor effects resulting in further lowering of blood pressure may occur.
Because adrenaline may cause hyperglycaemia, diabetic patients receiving adrenaline may require increased dosage of insulin or oral hyperglycaemia agents.
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. If used during pregnancy, adrenaline may cause anoxia to the foetus. For this reason parenteral adrenaline should not be used during the second stage of labour. Adrenaline should only be used during pregnancy if the potential benefits justify the possible risks to the foetus.
Adrenaline is distributed into breast milk. Breast-feeding should be avoided in mothers receiving adrenaline injection.
4.7 Effects on ability to drive and use machines
Not applicable in normal conditions of use.
4.8 Undesirable effects
Side effects such as anxiety, dyspnoea, hyperglycaemia, restlessness, palpitations, tachycardia, tremors, weakness, nausea, vomiting, sweating, dizziness, headache, and coldness of the extremities may occur even with small doses of adrenaline.
In patients with Parkinsonian Syndrome, adrenaline increases rigidity and tremor.
Adrenaline causes ECG changes including a decrease in T-wave amplitude in all leads in normal persons.
Disturbances of cardiac rhythm and rate may result in palpitation and tachycardia. Adrenaline can cause potentially fatal ventricular arrhythmias including fibrillation, especially in patients with organic heart disease or other receiving other drugs that sensitise the heart to arrhythmias.
Cerebral haemorrhage and pulmonary oedema have resulted from hypertension, following intramuscular administration of usual doses of adrenaline in susceptible subjects especially, in elderly patients.
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.
After overdose or inadvertent IV administration of usual intramuscular doses of adrenaline, systolic and diastolic blood pressure rise sharply; venous pressure also rises, which may lead to cerebral haemorrhage, pulmonary oedema and hemiplegia. Because 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 agents, such as 5 - 10mg of phentolamine mesylate, followed by a beta-adrenoreceptor blocking agent such as 2.5mg to 5mg of propranolol.
Adrenaline overdosage causes transient bradycardia followed by tachycardia and may cause other potentially fatal cardiac arrhythmias. Arrhythmias, if they occur, may be counteracted by propranolol injection. Kidney failure, metabolic acidosis and cold, white skin may also occur.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Adrenaline is a direct acting sympathomimetic agent, which exerts effects on both ^ and P adrenoceptors. It exhibits little selectivity towards and receptors but is significantly more selective to p2 than p1. Major effects include increased systolic blood pressure, reduced diastolic blood pressure, tachycardia, hyperglycaemia and hypokalaemia.
5.2 Pharmacokinetic properties
Pharmacologically active concentrations of adrenaline are not achieved following oral administration as it is rapidly oxidised and conjugated in the gastrointestinal mucosa and the liver. Absorption from subcutaneous tissue is slow due to local vasoconstriction; effects are produced within 5 minutes. Absorption is more rapid after intramuscular injection than after subcutaneous injection.
Adrenaline is rapidly distributed into the heart, spleen, several glandular tissues and adrenergic nerves. It readily crosses the placenta and is approximately 50% bound to plasma proteins.
Adrenaline is rapidly metabolised in the liver, neuronal tissues and elsewhere. Up to 91% of the intravenous dose is excreted in the urine, but only 1% of the dose can be recovered unchanged.
5.3 Preclinical safety data
There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Sodium Chloride Citric Acid monohydrate Sodium Citrate Dihydrate Sodium Metabisulphite Water for Injections Nitrogen
6.2 Incompatibilities
Adrenaline is rapidly denatured by oxidising agents and alkalis including sodium bicarbonate, halogens, nitrates, nitrites, and salts of iron, copper and zinc. Adrenaline may be mixed with 0.9% sodium chloride injection but is incompatible with 5% sodium chloride injection. The stability of adrenaline in 5% dextrose injection decreases when the pH is greater than 5.5.
6.3 Shelf life
15 months
6.4 Special precautions for storage
Do not store above 25°C. Store in the original container.
6.5 Nature and contents of container
This product is available in 1ml, 5ml and 10ml sterile aqueous solution in glass (Type 1) ampoules. Packed into cartons of 10 ampoules. Also available as single packs of 1ml, 5ml and 10ml ampoules.
6.6 Instructions for use/handling
Protect product from light.
7 MARKETING AUTHORISATION HOLDER
Aurum Pharmaceuticals Ltd Bampton Road,
Harold Hill,
Romford,
Essex RM3 8UG
Distributed by
Martindale Pharmaceuticals
Bampton Rd
Romford
RM3 8UG
UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 12064/0018
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
2 November 1999
10 DATE OF REVISION OF THE TEXT
16/03/2011