Adrenaline Injection Bp (1:10000) 100 Micrograms In 1ml
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Adrenaline (Epinephrine) Injection BP (1:10,000) 100 micrograms in 1ml.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each ml contains 100 micrograms of Adrenaline (Epinephrine) as Acid Tartrate BP.
3 PHARMACEUTICAL FORM
Sterile Solution for Injection.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Paediatric Cardiopulmonary Resuscitation (CPR).
4.2 Posology and method of administration
The dosage regimen of Adrenaline Injection in Paediatric Advanced Life Support reflects the recommendations of the Resuscitation Council UK, (Guidelines 2005).
Adults, the elderly and children over 12 years
Not recommended.
Children under 12 years
Perform Continuous CRP (see guidelines)
• Give adrenaline:
- If venous or intraosseous (IO) access has been established, give adrenaline 10 microgram kg-1 (0.1 ml kg-1 of 1 in 10,000 solution).
- If there is no circulatory access, attempt to obtain IO access.
- If circulatory access is not present, and cannot be quickly obtained, but the patient has a tracheal tube in place, consider giving adrenaline 100 microgram kg-1 via the tracheal tube (1 ml kg-1 of 1 in 10,000 or 0.1 ml kg-1 in 1,000 solution). This is the least satisfactory route (see routes of drug administration).
• Continue CPR.
• Repeat the cycle:
- Give adrenaline 10 microgram kg-1 every 3 to 5 minutes, (i.e. every
other loop), while continuing to maintain effective chest compression and
ventilation without interruption.
Unless there are exceptional circumstances, the dose should be 10 microgram kg-1 again for this and subsequent doses.
4.3 Contraindications
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, if 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 10000 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.
Care should be exercised in patients who suffer from hypertension.
Extreme care is also needed in conditions which predispose a patient to adverse effects on the heart, such as hyperthyroidism.
4.5 Interaction 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.
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.
4.6 Pregnancy and lactation
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.
4.8 Undesirable effects
Side effects such as anxiety, dyspnoea, hyperglycaemia, restlessness, palpitations, tachycardia, tremors, weakness, 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.
Subarachnoid haemorrhage and hemiplegia have resulted from hypertension, even following subcutaneous administration of usual doses of adrenaline.
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.
4.9 Overdose
After overdose or inadvertent IV administration of usual subcutaneous doses of adrenaline, systolic and diastolic blood pressure rise sharply; venous pressure also rises. Cerebrovascular or other haemorrhage and hemiplegia may result, especially in elderly patients. 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 an active principle of the adrenal medulla which is used as a direct-acting sympathomimetic agent. Adrenaline has a somewhat more marked effect on beta-adrenoceptors than on alpha-adrenoceptors. In addition, its actions vary considerably according to the dose given, and the consequent reflex compensating responses of the body. Adrenaline produces marked and concentration-dependent increases in stroke volume, cardiac output and systemic vascular resistance when arterial plasma concentration is increased from 0.3 to 6nmol/l (0.055 to 1.1pg/l).
In practice, major effects of adrenaline include increased speed and force of cardiac contraction (with lower doses this causes increased systolic pressure yet reduced diastolic pressure since overall peripheral resistance is lowered, but with higher doses both systolic and diastolic pressure are increased as stimulation of peripheral alpha-receptors increases peripheral resistance); blood flow to skeletal muscle is increased (reduced with higher doses); metabolic effects include increased glucose output as well as markedly increased oxygen consumption; blood flow in the kidneys, mucosa, and skin is reduced; there is little direct effect on cerebral blood flow.
5.2 Pharmacokinetic properties
Adrenaline acts rapidly following intramuscular and subcutaneous injection; latter route is sometimes considered to be slower and less reliable for emergency use. Local vasoconstriction can slow absorption, but hastened by massaging injection site.
Adrenaline injected into the body, or released from the adrenal medulla is very rapidly inactivated by processes which include uptake into adrenergic neurones, diffusion, and enzymatic degradation in the liver and body tissues.
Adrenaline is rapidly distributed into the heart, spleen, several glandular tissues and adrenergic nerves. It is approximately 50% bound to plasma proteins.
Endogenous plasma concentrations of adrenaline in normal subjects are in the range 30 to 160 ng/l.
The decline of plasma adrenaline following intravenous infusion has been reported to be biexponential with a mean clearance of 9.4 l/min (range 4.914.6 l/min). The half lives of the fast and slow exponential phases are approximately
3 and 10 minutes respectively.
One of the enzymes responsible for the chemical inactivation of this exogenous or hormonal adrenaline is Catechol-O-methyltransferase (COMT), the other is monoamine oxidase (MAO).
In general:
The metabolites are excreted in the urine mainly as their glucuronide and ethereal sulphate conjugates. About 70-95% of an intravenous dose is excreted in the urine; of the excreted material, about 80% is excreted as O-methyl metabolites and 2% as catechol metabolites, and only 1% is excreted as unchanged drug.
Adrenaline is inactivated by the introduction of a methyl group by COMT. Thus the termination of the pharmacological response of Adrenaline (and other catecholamines) is not only dependent on MAO. However, in Adrenaline’s role as a neurotransmitter, it is enzymatically regulated by MAO.
Adrenaline crosses the placenta to enter foetal circulation.
Preclinical safety data
5.3
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 BP Citric Acid monohydrate BP Sodium Citrate dihydrate BP Sodium Metabisulphite BP Water for Injections BP Nitrogen NF
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
18 months.
6.4 Special precautions for storage
Do not store above 25 °C keep in outer carton.
Do not use if the contents of the syringe are discoloured.
6.5
Nature and contents of container
Type 1 borosilicate 1ml glass prefilled syringes containing 100 micrograms of Adrenaline in 1ml. Pack size 1 x 1ml syringe.
6.6 Instructions for use, Handling and disposal
Use once and discard any remaining solution at the end of the session. No needle is provided with this syringe.
7 MARKETING AUTHORISATION HOLDER
Aurum Pharmaceuticals Ltd
Bampton Road
Harold Hill
Romford
Essex
RM3 8UG
8 MARKETING AUTHORISATION NUMBER(S)
PL 12064/0041
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
30th September 1998 / 29th September 2003
10 DATE OF REVISION OF THE TEXT
24/04/2008