NAME OF THE MEDICINAL PRODUCT

Adrenaline (Epinephrine) Injection BP 1:1000

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each 1ml contains 1mg Adrenaline (Epinephrine) as Acid Tartrate. For excipients, see section 6.1.

PHARMACEUTICAL FORM

Sterile Solution for Injection.

CLINICAL PARTICULARS Therapeutic Indications

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

4.2 Posology and method of administration

The intramuscular (IM) route is recommended by the UK Resuscitation Council as the most appropriate for most individuals who have to give adrenaline to treat an anaphylactic reaction. The patient should be monitored as soon as possible (pulse, blood pressure, ECG, pulse oximetry). This will help monitor the response to adrenaline.

The best site for IM injection is the anterolateral aspect of the middle third of the thigh.

The subcutaneous route for adrenaline is not recommended for treatment of an anaphylactic reaction as it is less effective.

Dosage:

Adults:

500 micrograms (0.5ml) of 1:1000 adrenaline solution.

Elderly:

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

Children:

Volume of 1:1000 adrenaline to be administered is shown below

Over 12 years 0.5mg IM (0.5ml 1:1000 solution), 0.3mg IM (0.3ml 1:1000 solution if the child is small or prepubertal)

6 - 12 years 0.3mg IM (0.3ml 1:1000 solution) 6 months - 6 years 0.15mg IM (0.15ml 1:1000 solution)

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Under 6 months 0.01mg/Kg IM (0.01ml/Kg 1:1000 solution)

If necessary, these doses may be repeated several times at 5 - 15 minutes intervals according to blood pressure, pulse and respiratory function.

A small volume syringe should be used

Repeat the IM adrenaline dose if there is no improvement in the patient’s condition. If necessary, these doses may be repeated several times at 5 - 15 minutes intervals according to blood pressure, pulse and respiratory function.

A small volume syringe should be used.

The IM route for adrenaline is stated by the UK Resuscitation Council as the route of choice for most healthcare providers.

There is a much greater risk of causing harmful side effects by inappropriate dosage or misdiagnosis of anaphylaxis when using IV adrenaline. This is why the IM route is recommended for most healthcare providers.

The UK Resuscitation Council advises the IV adrenaline for anaphylaxis should be administered by those experienced in the use and titration of vasopressors in their normal clinical practice (e.g. anaesthetists, emergency physicians or intensive care doctors).

Intravenous adminstration of adrenaline for anaphylasis requires the use of a 1:10000 adrenaline solution.

Do not give the undiluted 1:1000 adrenaline intravenously.

4.3. Contra-Indications

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

4.4. Special Warnings and Special Precautions for Use

The IM route is generally preferred in the initial treatment of anaphylaxis, the IV route is generally more appropriate in the Intensive Care Unit (ICU) or Emergency Department (ED) setting. Adrenaline/Epinephrine injection 1:1000 (1mg/ml) is not suitable for IV use. If the adrenaline/epinephrine1:10000 (0.1mg/ml) injection is not available, adrenaline/epinephrine injection 1:1000 must be diluted to 1:10000 before IV use. The IV route for injection of adrenaline/epinephrine must be used with extreme caution and is best reserved for specialists familiar with IV use of epinephrine (adrenaline).

Adrenaline should be used with caution in patients with hyperthyroidism, diabetes mellitus, narrow angle glaucoma, hypertension, cerebrovascular disease, elderly patients, 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 should be used cautiously, if at all, during general anaesthesia with halogenated hydrocarbon anaesthetics.

Adrenaline should be used with caution during the second stage of labour (See Pregnancy and Lactation).

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 that can cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes, in certain susceptible individuals.

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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.

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 B-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

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.

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 (M.A.O.) is one of the enzymes responsible for adrenaline metabolism, M.A.O. inhibitors do not markedly potentiate the effects of adrenaline.

Adrenaline should not be used to counteract circulatory collapse or 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 hypoglycaemic 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

No specific effects are known. However the undesirable effects as listed below may have an effect. If so, patients are advised not to drive or operate machinery.

4.8. Undesirable Effects

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Side effects such as anxiety, tremor, tachycardia, arrhythmias, headache, cold extremities, also hypertension, pulmonary oedema, nausea, vomiting, sweating, weakness, dizziness and hyperglycaemia are reported.

In patients with parkinsonian syndrome, adrenaline increases rigidity and tremor.

Adrenaline causes E.C.G. 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 those receiving other drugs that sensitise the heart to arrhythmias.

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.

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: http://www.mhra.gov.uk/yellowcard

4.9. Overdose

Symptoms:    Arrhythmias, cerebral haemorrhage or pulmonary oedema

Treatment:    Adrenaline has a short duration of action, and the main treatment is supportive, but prompt

injection of phentolamine and propranolol may be of help.

5.    PHARMACOLOGICAL PROPERTIES

5.1.    Pharmacodynamic Properties

Adrenaline increases the force and speed of cardiac contractions, increases blood flow to skeletal muscle and relaxes bronchial musculature. Glucose is released into circulation, oxygen consumption is increased. Blood flow to the kidneys, mucosa and skin is reduced.

5.2. Pharmacokinetic Properties

The onset of action and peak effect after injection is rapid, and the duration short ( 1 - 2 hours).

Elimination is mainly via metabolism of the liver and sympathetic nerve endings, with a small amount excreted unchanged in the urine.

5.3. Pre-clinical Safety Data

None stated.

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6.    PHARMACEUTICAL PARTICULARS

6.1.    List of Excipients

Sodium Metabisulphite BP, Sodium Chloride BP and Water for Injection BP.

Ph adjustment may be made using either Hydrochloric acid BP or Sodium Hydroxide BP

6.2. Incompatibilities

Alkali’s and oxidising agents.

6.3. Shelf-Life

24 months.

6.4. Special Precautions for Storage

Protect from light.

6.5. Nature and Content of Container

0.5, 1, 2, 5, 10 ml in type 1 colourless neutral glass ampoules. Fusion sealed. Packed into cartons of 10 ampoules.

6.6. Instructions for Use, Handling and Disposal None applicable

7.    MARKETING AUTHORISATION HOLDER

Macarthys Laboratories Ltd T/A Martindale Pharmaceuticals,

Bampton Road,

Harold Hill,

Romford,

Essex,

England RM3 8UG

MARKETING AUTHORISATION NUMBER(S)

PL 01883/6118R

DATE OF FIRST AUTHORISATION / RENEWAL OF AUTHORISATION

First Authorised    06^th April 1990

Renewed    12^th April 1996

DATE OF REVISION OF THE TEXT

13/11/2015