ADRENALINE MARTINDALE 1mg/ml Solution for injection Ref.[115384] Active ingredients:

Source: Medicines & Healthcare Products Regulatory Agency (GB)  Revision Year: 2025  Publisher: Macarthys Laboratories Ltd, T/A Martindale Pharma, Bampton Road, Harold Hill, Romford, Essex, England, RM3 8UG

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1

Contraindications are relative as this product is intended for use in life-threatening emergencies.

  • Use in fingers, toes, ears, nose genitalia or buttocks owing to the risk of ischaemic tissue necrosis.
  • Do not use if solution is discoloured.

4.4. Special warnings and precautions for use

This product is for emergency use only and medical supervision of the patients is necessary after administration.

Adrenaline (Epinephrine) 1 mg/ml (1:1000) Solution for Injection 1mg/ml (1:1000) is not suitable for IV 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 or Emergency Department setting. Adrenaline (Epinephrine) 1mg/ml (1:1000) solution for injection is not suitable for IV use. If the adrenaline 0.1 mg/ml (1:10000) injection is not available, Adrenaline 1mg/ml (1:1000) solution must be diluted to 0.1 mg/mL (1:10000) before IV use. The IV route for injection of adrenaline must be used with extreme caution and is best reserved for specialists familiar with IV use of adrenaline.

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

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

Adrenaline may cause or exacerbate hyperglycaemia, blood glucose should be monitored, particularly in diabetic patients.

Repeated local administration may produce necrosis at the sites of injection.

Prolonged administration may induce metabolic acidosis, renal necrosis and tachyphylaxis.

Adrenaline should be avoided or used with extreme caution in patients undergoing anaesthesia with halothane or other halogenated anaesthetics, in view of the risk of inducing ventricular fibrillation.

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

Monitor the patient as soon as possible (pulse, blood pressure, ECG, pulse oximetry) in order to assess the response to adrenaline.

The best site for IM injection is the anterolateral aspect of the middle third of the thigh. The needle used for injection needs to be sufficiently long to ensure that the adrenaline is injected into muscle.

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

The presence of sodium metabisulfite 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/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.

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).

Antidepressant agents

Tricyclic antidepressants such as imipramine may potentiate the effects of adrenaline, especially on heart rhythm and rate.

Non-selective MAO inhibitors

Increased pressor action of adrenaline, usually moderate.

Selective MAO-A inhibitors, Linezolid (by extrapolation from non-selective MAO inhibitors): Risk of aggravation of pressor action.

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.

Phenothiazines

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.

Other medicinal products

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.

4.6. Fertility, pregnancy and lactation

Pregnancy

A teratogenic effect has been demonstrated in animal studies.

Adrenaline crosses the placenta. There is some evidence of a slightly increased incidence of congenital abnormalities. Injection of adrenaline may cause anoxia, fetal tachycardia, cardiac irregularities, extra systoles and louder heart sounds. Adrenaline usually inhibits spontaneous or oxytocin induced contractions of the 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. 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 outweigh the possible risks to the fetus.

Breast-feeding

Adrenaline is distributed into breast milk. Breast-feeding should be avoided in mothers receiving adrenaline injection.

Fertility

No data are available with respect to the impact of adrenaline on fertility.

4.7. Effects on ability to drive and use machines

Not applicable in normal conditions of use.

4.8. Undesirable effects

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.

Metabolism and nutrition disorders

Frequency not known: hyperglycaemia, hypokalaemia, metabolic acidosis.

Psychiatric disorders

Frequency not known: anxiety, nervousness, fear, hallucinations.

Nervous system disorders

Frequency not known: headache, tremors, dizziness, syncope.

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

Eye disorders

Frequency not known: mydriasis.

Cardiac disorders

Frequency not known: palpitations, tachycardia. In high dosage or for patients sensitive to adrenaline: cardiac dysrhythmia (sinus tachycardia, ventricular fibrillation/cardiac arrest), acute angina attacks, and risk of acute myocardial infarction.

Vascular disorders

Frequency not known: pallor, coldness of the extremities. In high dosage or for patients sensitive to adrenaline: hypertension (with risk of cerebral haemorrhage), vasoconstriction (for example cutaneous, in the extremities or kidneys)

Respiratory, thoracic and mediastinal disorders

Frequency not known: dyspnoea.

Gastrointestinal disorders

Frequency not known: nausea, vomiting.

General disorders and administration site conditions

Frequency not known: sweating, weakness

Repeated local injections may produce necrosis at sites of injection as a result of vascular constriction.

Reporting of suspected adverse reactions

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 Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

6.2. Incompatibilities

Adrenaline/epinephrine is rapidly denatured by oxidising agents and alkalis including sodium bicarbonate, halogens, nitrates, nitrites, and salts of iron, copper and zinc.

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