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Indications and Dosage
Intravenous
Acute hypotensive states Adult: Doses are expressed in terms of norepinephrine base: As a 4 mcg/mL solution: Initially, 2-3 mL/min (8-12 mcg/min). Dosage is individualised and adjusted to produce and maintain the desired haemodynamic effect. Usual maintenance dose: 0.5-1 mL/min (2-4 mcg/min). Dosage and treatment recommendations may vary among countries and individual products (refer to specific product guidelines).
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Reconstitution
Dilute with dextrose 5% in water, dextrose 5% in water and NaCl 0.9%, or NaCl 0.9% (however, dilution in NaCl 0.9% is not recommended) up to a final concentration of 4-64 mcg/mL. Premixed solutions for IV infusion are also available. Instructions for reconstitution may vary among countries and individual products. Refer to specific product guidelines.
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Incompatibility
Incompatible with alkali and oxidising agents, barbiturates, chlorphenamine, chlorothiazide, nitrofurantoin, novobiocin, phenytoin, Na bicarbonate, Na iodide, streptomycin, and insulin.
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Contraindications
Concomitant use with halothane and cyclopropane anaesthetics.
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Special Precautions
Patient with profound hypoxia or hypercarbia; coronary mesenteric or peripheral vascular thrombosis, Prinzmetal's angina, diabetes, hypertension, hyperthyroidism; ischaemic heart disease, elevated intracranial pressure; hypotension after a MI. Not for use in patients with hypotension associated with hypovolaemia; correct hypovolaemia prior to administration. Blood volume replacement can be given before and/or during use of norepinephrine; however, for cases wherein whole blood or blood plasma is needed to increase the blood volume, administer separately. Avoid abrupt withdrawal. Obese patient. Hepatic and severe renal impairment. Neonates and elderly. Pregnancy and lactation.
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Adverse Reactions
Significant: Extravasation (may lead to tissue necrosis); severe peripheral and visceral vasoconstriction, decreased renal perfusion and urine output, tissue hypoxia, lactic acidosis, and decreased systemic blood flow even with normal blood pressure (continuous administration in the absence of blood volume replacement); ventricular tachycardia or fibrillation (patient with profound hypoxia or hypercarbia); plasma volume depletion (prolonged administration); severe hypotension (abrupt withdrawal); gangrene of the extremities.
Cardiac disorders: Bradycardia, cardiogenic shock, stress cardiomyopathy, focal myocarditis. Eye disorders: Acute glaucoma. Gastrointestinal disorders: Nausea, vomiting. Investigations: ECG change. Nervous system disorders: Headache, dizziness, tremor. Psychiatric disorders: Anxiety, insomnia. Respiratory, thoracic and mediastinal disorders: Dyspnoea. Vascular disorders: Hypertension, peripheral ischaemia, gangrene. Potentially Fatal: Cardiac arrhythmias, ventricular tachycardia and ventricular fibrillation. |
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IM/IV/Parenteral: C
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Monitoring Parameters
Monitor vital signs, blood pressure (alternatively, mean arterial pressure), heart rate, intravascular volume status, urine output, peripheral perfusion; cardiac output, pulmonary capillary wedge pressure (as necessary). Assess infusion site for signs of extravasation.
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Overdosage
Symptoms: Severe hypertension, reflex bradycardia, marked increase in peripheral resistance and reduced cardiac output, cerebral haemorrhage, photophobia, pallor, intense sweating, vomiting, retrosternal pain, and severe headache. Management: Symptomatic and supportive treatment.
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Drug Interactions
Increased risk of severe, prolonged hypertension with MAOIs, Linezolid, and TCAs.
Potentially Fatal: Increased risk of tachycardia or ventricular fibrillation with halogenated anaesthetics (e.g. cyclopropane, desflurane, isoflurane). |
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Action
Description:
Mechanism of Action: Norepinephrine is a sympathomimetic amine. It is an α-adrenergic receptor agonist that causes peripheral vasoconstriction and a β1 agonist as an inotropic stimulator of the heart and dilator of coronary arteries, thereby increasing systemic blood pressure and coronary artery blood flow. Synonym(s): Noradrenaline. Onset: Rapid. Duration: Vasopressor: 1-2 minutes. Pharmacokinetics: Distribution: Crosses the placenta but does not readily penetrate the blood-brain barrier. Volume of distribution: 8.8 L. Plasma protein binding: Approx 25% mainly to albumin with smaller portion to prealbumin and α1-acid glycoprotein. Metabolism: Extensively metabolised via methylation by COMT and via deamination by monoamine oxidase (MAO) into the major inactive metabolites 4-hydroxy-3-methoxymandelic acid and normetanephrine. Excretion: Via urine (as metabolites; small amount as unchanged drug). Elimination half-life: Approx 2-4 minutes. |
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Chemical Structure
 Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 439260, Norepinephrine. https://pubchem.ncbi.nlm.nih.gov/compound/Norepinephrine. Accessed Nov. 21, 2023. |
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Storage
Store between 15-30°C. Protect from light. Diluted solution: Store between 20-25°C. Protect from light. Storage recommendations may vary among countries and individual products. Refer to specific product guidelines.
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MIMS Class
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ATC Classification
C01CA03 - norepinephrine ; Belongs to the class of adrenergic and dopaminergic cardiac stimulants excluding glycosides. Used in the treatment of hypotension.
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References
Anon. Noradrenaline [Norepinephrine]. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 27/06/2023. Anon. Norepinephrine (Pediatric and Neonatal Lexi-Drugs). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 13/10/2023. Anon. Norepinephrine. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 27/06/2023. Boucher & Muir Pty Ltd. Noradrenaline BNM Concentrate for IV injection data sheet 15 December 2020. Medsafe. http://www.medsafe.govt.nz. Accessed 27/06/2023. Buckingham R (ed). Noradrenaline. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 27/06/2023. Joint Formulary Committee. Noradrenaline/Norepinephrine. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 27/06/2023. Levophed (Hospira Inc.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 27/06/2023. Noradrenaline 1 mg/mL Concentrate for Solution for Infusion (Wockhardt UK Ltd). MHRA. https://products.mhra.gov.uk. Accessed 27/06/2023. Noradrenaline Kabi 1 mg/mL Concentrate for Solution for Infusion (Fresenius Kabi Deutschland GmbH). MHRA. https://products.mhra.gov.uk. Accessed 27/06/2023. Norepinephrine Bitartrate (Baxter Healthcare Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 27/06/2023. Norepinephrine. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 27/06/2023. Paediatric Formulary Committee. Noradrenaline/Norepinephrine. BNF for Children [online]. London. BMJ Group, Pharmaceutical Press, and RCPCH Publications. https://www.medicinescomplete.com. Accessed 13/10/2023. Vipranop 5 micrograms/mL Solution for Injection and Infusion (Laboratoire Aguettant). MHRA. https://products.mhra.gov.uk. Accessed 27/06/2023.
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