Adult: For temporary relief of mild symptoms of intermittent cases: As 2.25% racepinephrine solution for nebulisation (equivalent to 1% epinephrine): 1-3 inhalations, may be repeated after ≥3 hours as necessary. Max: 12 inhalations per 24 hours. Child: ≥4 years Same as adult dose.
Intramuscular, Subcutaneous Anaphylaxis
Adult: For emergency treatment of allergic reactions associated with insect stings or bites, foods, drugs, and other allergens, as well as idiopathic or exercise-induced cases: As auto-injector (self-administration): 0.3 mg; may administer a 2nd dose 5-15 minutes after the 1st inj if there is no clinical improvement or if deterioration occurs. If more than 2 sequential doses are needed, doses must be given under direct medical supervision. As 1 mg/mL (1:1,000) solution: 0.2-0.5 mg (0.2-0.5 mL), may be repeated every 5-15 minutes as necessary. Administer doses via IM (preferred) or SC inj into the anterolateral aspect of the thigh (through clothing if necessary). Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines). Child: As auto-injector (self- or caregiver-administration): Patients weighing 15-<30 kg: 0.15 mg; ≥30 kg: 0.3 mg; may administer a 2nd dose 5-15 minutes after the 1st inj if there is no clinical improvement or if deterioration occurs. Doses are given via IM (preferred) or SC inj into the anterolateral aspect of the thigh (through clothing if necessary). As 1 mg/mL (1:1,000) solution: 0.01 mg/kg (0.01 mL/kg) via IM or SC inj. Max: ≤30 kg: 0.3 mg (0.3 mL) per dose; >30 kg: 0.5 mg (0.5 mL) per dose. If necessary, dose may be repeated every 5-15 minutes. Alternative age-specific dosing (as 1 mg/mL solution): <6 months 0.01 mg/kg (0.01 mL/kg); 6 months to 5 years 0.15 mg (0.15 mL); 6-12 years 0.3 mg (0.3 mL); >12 years 0.5 mg (0.5 mL); doses are given via IM inj, may be repeated every 5-15 minutes according to patient response. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
Adult: As 0.1 mg/mL (1:10,000) solution: 1 mg (10 mL) every 3-5 minutes as necessary until return of spontaneous circulation, given via slow IV inj or via intraosseous route. Recommendations may vary among local guidelines (refer to specific country guidelines). Child: As 0.1 mg/mL (1:10,000) solution: 0.01 mg/kg (0.1 mL/kg) every 3-5 minutes as necessary until return of spontaneous circulation, given via slow IV inj or via intraosseous route. Max: 1 mg/dose. Recommendations may vary among local guidelines (refer to specific country guidelines).
Intravenous Anaphylactic shock
Adult: As 0.1 mg/mL (1:10,000) solution: 0.1-0.25 mg (1-2.5 mL) via slow IV inj. Dose may be repeated every 5-15 minutes as necessary or followed by IV infusion at a rate of 0.001-0.004 mg/min. Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
Reconstitution
IV: 1 mg/mL solution may be diluted with a suitable diluent to prepare the 0.1 mg/mL solution. Continuous IV infusion: Neonates: Dilute with a compatible IV solution (e.g. dextrose 5% inj) to a standard concentration of 10 mcg/mL. Recommendations on dilution or concentration may vary among local guidelines (refer to specific country guidelines).
Incompatibility
Oxidising agents and alkalis including sodium bicarbonate, halogens, nitrates, nitrites, and salts of iron, zinc, and copper may rapidly denature epinephrine. Incompatible with NaCl 5% inj.
Contraindications
Concomitant use with halogenated hydrocarbons (e.g. halothane) or cyclopropane during general anaesthesia; concurrent administration with local anaesthetics in certain areas (e.g. ears, fingers, toes). Inhalation (when used for self-medication): Concomitant use with or within 2 weeks of discontinuing MAOI therapy. Contraindications may vary among individual products (refer to specific product guidelines).
Special Precautions
Patient with CV disease (e.g. arrhythmias, obstructive cardiomyopathy, angina pectoris, cor pulmonale, atherosclerosis, hypertension), cerebrovascular disease, organic brain damage; Parkinson's disease, hyperthyroidism, phaeochromocytoma, narrow-angle glaucoma, high IOP, diabetes mellitus, hypokalaemia, hypercalcaemia; long-standing bronchial asthma and emphysema (who may also has degenerative heart disease); hyperreflexia, shock (other than anaphylactic shock); prostatic hypertrophy or urinary hesitancy, psychoneurotic disorder. Avoid extravasation during IV administration. Avoid use during the 2nd stage of labour or when maternal systolic/diastolic blood pressure exceeds 130/80 mmHg. Obese patient. Renal impairment. Neonates, children, and elderly. Pregnancy and lactation.
Adverse Reactions
Significant: New-onset or exacerbation of angina pectoris, cardiac arrhythmias, myocardial ischaemia, pulmonary oedema, oliguria; transient blood glucose elevations (particularly in diabetic patients); metabolic acidosis (prolonged use); psychomotor agitation or temporary worsening of symptoms (e.g. rigidity, tremor) in patients with Parkinson's disease; peripheral ischaemia (accidental inj into fingers, hands, or feet). Rarely, serious skin and soft tissue infections at the inj site (e.g. necrotising fasciitis, gas gangrene). Cardiac disorders: Tachycardia, palpitations. Rarely, stress cardiomyopathy. Gastrointestinal disorders: Nausea, vomiting. General disorders and administration site conditions: Asthenia. Nervous system disorders: Headache, dizziness, tremor. Psychiatric disorders: Anxiety. Skin and subcutaneous tissue disorders: Hyperhidrosis, pallor. Vascular disorders: Hypertension.
Monitor heart rate, blood pressure (invasive blood pressure while receiving continuous infusion), cardiac status (constantly during continuous infusion). Correct blood volume optimally before initiating treatment. Monitor infusion site for blanching or extravasation. Assess for cardiac arrhythmias, hyperlactataemia, and hyperglycaemia. For inhalation use: Monitor vital signs, FEV1, peak flow, and other pulmonary function tests; CNS stimulation, asthma symptoms. Refer to local policies and guidelines for further information.
Overdosage
Symptoms: Rapid increase in systolic and diastolic blood pressure resulting in cerebrovascular haemorrhage or other haemorrhages and hemiplegia; transient bradycardia followed by tachycardia, cardiac arrhythmias; pulmonary oedema due to peripheral vascular constriction along with cardiac stimulation; kidney failure, metabolic acidosis, pallor, coldness of the skin. Management: Supportive treatment. Administer rapidly acting α-adrenoceptor blocking agents (e.g. phentolamine) to counteract pressor effects. In case of pulmonary oedema which interferes with respiration, administer rapidly acting α-adrenergic blocking agents and/or intermittent positive-pressure respiration. Administer β-adrenergic blockers (e.g. propranolol) to treat arrhythmias.
Drug Interactions
Increased risk of severe, prolonged hypertension with MAOIs. May cause additive effect and increase the risk of toxicity with other sympathomimetic agents. May potentiate α-adrenergic action with oxytocin. Vasoconstrictive and hypertensive effects may be antagonised by rapidly acting vasodilators (e.g. nitrates) or α-adrenergic blockers (e.g. phentolamine). May cause severe hypertension and reflex bradycardia with non-selective β-blocking agents (e.g. propranolol). β-blocking agents may antagonise the cardiac and bronchodilating effects of epinephrine. Ergot alkaloids may reverse the pressor effect of epinephrine. TCAs (e.g. imipramine) may potentiate the effect of epinephrine, which increases the risk of hypertension and cardiac arrhythmias. May potentiate arrhythmogenic effect with certain antihistamines (e.g. diphenhydramine), cardiac glycosides, quinidine, and thyroid hormones. May increase the risk of hypokalaemia with K-depleting diuretics, corticosteroids, aminophylline, and theophylline. May inhibit insulin secretion which may result in loss of blood glucose control in diabetic patients; dosage adjustment of insulin or oral hypoglycaemic agents may be needed. May reverse the antihypertensive effects of adrenergic neuron blockers (e.g. guanethidine). Potentially Fatal: May increase the risk of arrhythmias, including ventricular premature contractions, tachycardia or fibrillation with halogenated hydrocarbon anaesthetics (e.g. halothane) or other anaesthetics (e.g. cyclopropane).
Food Interaction
Alcohol may potentiate the therapeutic effect of epinephrine.
Action
Description: Mechanism of Action: Epinephrine is a direct-acting sympathomimetic agent. It acts on α-, β1-, and β2-adrenergic receptors causing relaxation of smooth muscle of the bronchial tree, cardiac stimulation, and dilation of skeletal muscle vasculature. Synonym(s): Adrenaline. Onset: Bronchodilation: Approx 1 minute (inhalation); 5-10 minutes (SC). Pharmacokinetics: Absorption: Well absorbed following IM or SC inj. Distribution: Crosses the placenta and enters breast milk. Plasma protein binding: Approx 50%. Metabolism: Undergoes uptake into adrenergic neurons and metabolised by monoamine oxidase (MAO) and COMT. Excretion: Via urine (as metabolites, mainly glucuronide and ethereal sulfate conjugates). Elimination half-life: <5 minutes (IV).
Chemical Structure
Epinephrine Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5816, Epinephrine. https://pubchem.ncbi.nlm.nih.gov/compound/Epinephrine. Accessed Aug. 22, 2023.
Storage
Auto-injector: Store below 30°C. Protect from light. Do not freeze or refrigerate. Solution for inj: Store below 25°C. Protect from light. Solution for nebulisation: Store between 2-25°C. Protect from light and excessive heat. Do not freeze. Storage recommendations may vary between products (refer to specific product guidelines).
R03AA01 - epinephrine ; Belongs to the class of adrenergic inhalants, alpha- and beta-adrenoreceptor agonists. Used in the treatment of obstructive airway diseases. C01CA24 - epinephrine ; Belongs to the class of adrenergic and dopaminergic cardiac stimulants excluding glycosides. Used in the treatment of hypotension.
References
Adrenalin Injection (Par Pharmaceuticals, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 08/05/2023.Adrenaline 1:1,000 (1 mg/mL) Solution for Injection (Bradex S.A.). MHRA. https://products.mhra.gov.uk. Accessed 28/07/2023.Anon. Adrenaline [Epinephrine] (Oral Inhalation). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/05/2023.Anon. Adrenaline [Epinephrine] (Systemic). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/05/2023.Anon. Epinephrine (Systemic) (Pediatric and Neonatal Lexi-Drugs). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 08/05/2023.Anon. Epinephrine. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 08/05/2023.Asthmanefrin Solution (Nephron Pharmaceuticals Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 08/05/2023.Buckingham R (ed). Adrenaline. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/05/2023.Buckingham R (ed). Anaphylaxis and Anaphylactic Shock (Cardiovascular Drugs - Adrenaline). Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 28/07/2023.Ephedrix 1 mg/mL Solution for Injection (Endure Medical, Inc.). MIMS Philippines. http://www.mims.com/philippines. Accessed 08/05/2023.Epinephrine. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 08/05/2023.Epipen Auto-injector 0.3 mg (Mylan Products Ltd.). MHRA. https://products.mhra.gov.uk. Accessed 08/05/2023.Epipen Injection and Epipen Jr Injection (Mylan Specialty L.P.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 08/05/2023.Epipen Jr. Auto-injector 0.15 mg (Mylan Products Ltd.). MHRA. https://products.mhra.gov.uk. Accessed 08/05/2023.Jext 150 mcg Solution for Injection in Pre-filled Pen (ALK-Abelló A/S). MHRA. https://products.mhra.gov.uk. Accessed 28/07/2023.Joint Formulary Committee. Adrenaline/Epinephrine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 08/05/2023.Paediatric Formulary Committee. Adrenaline/Epinephrine. BNF for Children [online]. London. BMJ Group, Pharmaceutical Press, and RCPCH Publications. https://www.medicinescomplete.com. Accessed 08/05/2023.Pfizer New Zealand Limited. DBL Adrenaline 1:1,000 (1 mg/mL) and 1:10,000 (1 mg/10 mL) Solution for Injection data sheet 15 July 2021. Medsafe. http://www.medsafe.govt.nz. Accessed 08/05/2023.Tacarline Injection 1 mg/mL (Duopharma [M] Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 28/07/2023.Viatris Ltd. Epipen 300 mcg Auto-injector data sheet 10 December 2021. Medsafe. http://www.medsafe.govt.nz. Accessed 08/05/2023.Viatris Ltd. Epipen Jr 150 mcg Auto-injector data sheet 10 December 2021. Medsafe. http://www.medsafe.govt.nz. Accessed 08/05/2023.
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