Noradrenalin Laboratoire Aguettant 1 mg/ml (Norepinephrine Concentrate)
Vasopressor concentrate for solution for infusion — emergency treatment of acute hypotension and septic shock
Quick facts about Noradrenalin Laboratoire Aguettant
Key Takeaways
- Concentrate requires dilution: The 1 mg/ml formulation is a concentrate and must be diluted before infusion; typical final concentrations are 4 to 40 micrograms/ml (base) in 5% glucose or glucose–saline
- First-line vasopressor for septic shock: Norepinephrine is recommended as the first-choice vasopressor by the Surviving Sepsis Campaign 2021 guidelines for hemodynamic support in septic shock
- Central venous access required: Must be given through a central venous catheter; peripheral administration can cause severe tissue necrosis from extravasation
- Continuous hemodynamic monitoring: Invasive blood pressure, electrocardiogram, and infusion site surveillance are mandatory throughout treatment
- Gradual weaning only: Abrupt discontinuation can trigger rebound hypotension; always taper the infusion rate gradually while observing hemodynamic response
What Is Noradrenalin Laboratoire Aguettant and What Is It Used For?
Noradrenalin Laboratoire Aguettant 1 mg/ml contains norepinephrine (noradrenaline), a potent endogenous catecholamine that constricts blood vessels to raise blood pressure. It is used exclusively in adult patients in hospital critical care settings for the emergency treatment of acute hypotension (dangerously low blood pressure), most notably septic shock, cardiogenic shock with low systemic vascular resistance, and post-cardiotomy hypotension.
Norepinephrine is the principal neurotransmitter of the sympathetic nervous system and is also released as a hormone by the adrenal medulla. It plays a central role in the body's cardiovascular response to stress, injury, and blood loss by redistributing blood flow, maintaining perfusion pressure to vital organs, and supporting cardiac function. As a pharmaceutical agent, synthetic norepinephrine tartrate reproduces the actions of this endogenous hormone, primarily by stimulating alpha-1 adrenergic receptors on vascular smooth muscle, producing rapid and powerful vasoconstriction that raises systolic and diastolic blood pressure and increases mean arterial pressure (MAP).
In clinical practice, norepinephrine is recommended as the first-line vasopressor in septic shock by the Surviving Sepsis Campaign (SSC) 2021 International Guidelines, by the European Society of Intensive Care Medicine (ESICM), and by the Society of Critical Care Medicine (SCCM). Compared with alternative vasopressors such as dopamine, norepinephrine produces more reliable restoration of target mean arterial pressure with fewer tachyarrhythmic events and is associated with improved survival in large randomised clinical trials including the seminal SOAP II trial by De Backer and colleagues (NEJM 2010).
Beyond septic shock, the 1 mg/ml concentrate of Noradrenalin Laboratoire Aguettant is used in a wide range of critical care scenarios. These include cardiogenic shock (typically in combination with inotropic agents such as dobutamine), neurogenic shock following spinal cord injury, post-cardiopulmonary bypass vasoplegia after cardiac surgery, anaphylactic shock refractory to adrenaline, and selected cases of hepatorenal syndrome where it may improve renal perfusion pressure. Its potent alpha-adrenergic vasoconstrictive effect is particularly valuable when systemic vascular resistance is abnormally low, as in distributive shock states.
The Noradrenalin Laboratoire Aguettant 1 mg/ml formulation is supplied as a concentrated solution in ampoules or vials that must be diluted in a compatible carrier fluid prior to administration. This differs from the 0.08 mg/ml ready-to-use solution also produced by Laboratoire Aguettant, which can be infused directly without further dilution. The concentrate format offers flexibility for institutions that prefer to tailor the final infusion concentration to the patient's required dose and fluid tolerance, while the ready-to-use option reduces the risk of preparation errors. Both formulations deliver identical pharmacology.
Vasopressor therapy with norepinephrine should be part of a comprehensive hemodynamic management strategy. Adequate fluid resuscitation should be initiated before or concurrently with vasopressor therapy, in accordance with current SSC guidelines. Norepinephrine alone cannot correct hypovolemia, and initiating it in a volume-depleted patient without simultaneous fluid replacement can worsen tissue perfusion, accelerate organ injury, and mask the true underlying cause of hypotension.
What Should You Know Before Taking Noradrenalin Laboratoire Aguettant?
Noradrenalin Laboratoire Aguettant 1 mg/ml must never be administered undiluted, through a peripheral intravenous line, or in the absence of continuous hemodynamic monitoring. It is contraindicated in patients with known hypersensitivity to norepinephrine or any excipient. Several pre-existing conditions require careful risk-benefit assessment before starting treatment.
Contraindications
Norepinephrine is contraindicated in the following situations:
- Undiluted administration: The 1 mg/ml concentrate must never be administered without prior dilution; doing so can cause immediate fatal hypertension and vascular injury
- Peripheral venous administration: Must never be given via a peripheral cannula or peripheral vein due to the risk of severe local tissue ischemia and necrosis from extravasation
- Known hypersensitivity: In patients with documented allergy to norepinephrine or any of the excipients (sodium chloride, disodium edetate, hydrochloric acid, sodium hydroxide, water for injections)
- Existing peripheral or mesenteric vascular thrombosis: Vasoconstriction may extend thrombosis and worsen ischemic injury in the affected vascular bed
- Profound hypoxia or hypercapnia: Until corrected, as these conditions markedly increase the risk of catecholamine-induced ventricular arrhythmias
These contraindications must be balanced against the clinical urgency. In life-threatening hypotensive emergencies where no alternative exists, the treating physician may still need to initiate norepinephrine while actively correcting contributing factors. Any such decision rests on rigorous individual risk-benefit assessment.
Warnings and Precautions
Enhanced vigilance and additional monitoring are required in patients with the following conditions:
- Severe left ventricular dysfunction or low cardiac output states: Norepinephrine markedly increases afterload (the resistance against which the heart pumps), which can further impair stroke volume in patients with severely compromised systolic function. Continuous cardiac output monitoring (via pulmonary artery catheter, pulse contour analysis, or echocardiography) is recommended.
- Recent myocardial infarction or unstable ischemic heart disease: Increased cardiac workload, coronary vasoconstriction, and enhanced myocardial oxygen demand may extend infarct size or precipitate new ischemia.
- Pre-existing cardiac arrhythmias: Norepinephrine's beta-1 adrenergic activity can aggravate tachyarrhythmias, atrial fibrillation, and ventricular ectopy; continuous ECG monitoring is mandatory.
- Hyperthyroidism: Patients with thyrotoxicosis have heightened cardiovascular sensitivity to catecholamines and are at elevated risk of severe hypertension, tachyarrhythmias, and thyroid storm.
- Diabetes mellitus: Norepinephrine promotes glycogenolysis and hepatic gluconeogenesis, exacerbating hyperglycemia; glucose monitoring should be intensified.
- Hypovolemic hypotension: Low blood pressure caused primarily by volume depletion should be treated with fluid replacement. Using norepinephrine to mask hypovolemia can produce dangerously severe vasoconstriction with reduced tissue perfusion and organ injury.
- Peripheral vascular disease: Including Raynaud's phenomenon, peripheral arterial occlusive disease, and Buerger's disease. The vasoconstrictive effects of norepinephrine can critically compromise blood flow to already ischemic extremities, occasionally precipitating gangrene.
- Elderly patients: Reduced cardiovascular reserve, increased arterial stiffness, and higher prevalence of comorbidities make elderly patients more sensitive to pressor effects; cautious titration is advised.
- Renal or hepatic impairment: While the pharmacokinetics of norepinephrine are minimally altered in organ dysfunction, severely reduced renal blood flow during infusion can compound pre-existing kidney injury.
Throughout the infusion, the critical care team will continuously monitor blood pressure (preferably via an arterial line), electrocardiogram, urine output, peripheral perfusion, central venous pressure where available, and the infusion site for any sign of extravasation or line complication. If blood or plasma transfusion is required concurrently, it must be administered through a separate dedicated line to avoid physicochemical incompatibility.
If norepinephrine leaks from the vein into surrounding tissue (extravasation), the drug's intense vasoconstrictive effect can cause severe local ischemia, blanching, and progression to full-thickness necrosis within hours. If extravasation is suspected, the infusion must be stopped immediately (while ensuring continued hemodynamic support through an alternative line), and the affected area should be infiltrated subcutaneously with phentolamine 5–10 mg diluted in 10–15 ml of 0.9% sodium chloride, an alpha-adrenergic blocker that reverses the local vasoconstriction. Topical nitroglycerin ointment has also been described. Early recognition and treatment dramatically reduces the risk of permanent tissue loss.
Pregnancy and Breastfeeding
Norepinephrine should only be used during pregnancy when the potential benefit to the mother outweighs the potential risk to the fetus. Animal studies and limited clinical data suggest that norepinephrine can reduce uterine artery blood flow and uteroplacental perfusion, which may compromise fetal oxygenation and contribute to fetal distress. In pregnant patients with septic shock, obstetric shock, or anaphylaxis, the life-threatening nature of maternal hypotension typically outweighs the theoretical fetal risk, and norepinephrine may be used as a life-saving intervention under close multidisciplinary supervision.
Data regarding the excretion of norepinephrine into breast milk are limited. Given that this medicinal product is used exclusively in acute critical care settings and has an extremely short half-life (2–3 minutes), breastfeeding considerations are generally secondary to the immediate life-threatening condition being treated. The treating team, in consultation with neonatology and obstetric colleagues, will advise on the appropriate timing for resuming breastfeeding once the mother has stabilized.
Use in Children and Adolescents
The 1 mg/ml Noradrenalin Laboratoire Aguettant is not specifically licensed for paediatric use. However, norepinephrine is widely used off-label in paediatric intensive care for septic shock, cardiogenic shock, and post-operative cardiac surgery hypotension, following specialist protocols and weight-based dilution calculations. Paediatric intensivists typically prepare dilutions at significantly lower concentrations (commonly 0.04–0.4 mg/ml in neonates and children). Paediatric dosing should only be undertaken by clinicians experienced in paediatric critical care pharmacology.
Sodium Content and Excipient Considerations
Each ampoule of Noradrenalin Laboratoire Aguettant 1 mg/ml contains sodium chloride as a tonicity agent. When diluted in large-volume carrier fluids such as 5% glucose or glucose–saline, the sodium load delivered to the patient is generally negligible in the context of critical care fluid therapy. However, in patients on strict sodium-restricted regimens (severe heart failure, advanced renal impairment), the cumulative sodium from all intravenous sources should be tracked. The product also contains disodium edetate (EDTA) as a stabilizer; hypersensitivity to EDTA is extremely rare but has been reported.
How Does Noradrenalin Laboratoire Aguettant Interact with Other Drugs?
Norepinephrine has clinically significant interactions with several drug classes, including halogenated anesthetics, tricyclic antidepressants, SNRIs, MAO inhibitors (including linezolid and methylene blue), guanethidine, and oxytocic agents. These interactions can produce hypertensive crisis, severe cardiac arrhythmias, or dangerously potentiated pressor response.
Drug interactions with norepinephrine are of exceptional clinical importance because the consequences can be immediately life-threatening and may manifest within minutes of initiating the infusion. The vasopressor and cardiac effects of norepinephrine can be dramatically amplified by any drug that inhibits its metabolism (by MAO or COMT), blocks its reuptake at sympathetic nerve terminals, sensitizes the myocardium to catecholamines, or enhances adrenergic signalling. A thorough medication reconciliation must be performed prior to starting therapy, and critical-care nurses and physicians should remain continuously vigilant for new interacting agents being added during the ICU stay.
| Interacting Drug | Interaction Type | Clinical Effect | Severity |
|---|---|---|---|
| Halogenated volatile anesthetics (halothane, sevoflurane, desflurane, isoflurane) | Pharmacodynamic | Increased risk of ventricular arrhythmias; halogenated agents sensitize the myocardium to catecholamines | Major |
| Tricyclic antidepressants (imipramine, amitriptyline, nortriptyline) | Pharmacokinetic | Potentiated and prolonged pressor response due to blocked neuronal reuptake of norepinephrine | Major |
| SNRIs (venlafaxine, duloxetine, desvenlafaxine) | Pharmacokinetic | Enhanced vasopressor effect; risk of severe hypertension through inhibited reuptake | Major |
| Non-selective MAO inhibitors (phenelzine, tranylcypromine) | Pharmacokinetic | Hypertensive crisis; prevents breakdown of norepinephrine with markedly enhanced and prolonged effect | Major |
| Reversible MAO-A inhibitors (moclobemide) | Pharmacokinetic | Enhanced pressor response, though less extreme than with non-selective MAOIs | Major |
| Linezolid (oxazolidinone antibiotic) | Pharmacokinetic | Weak MAO-inhibiting activity; may potentiate pressor effect in ICU patients receiving both drugs | Moderate |
| Methylene blue | Pharmacokinetic | Inhibits MAO, increasing circulating norepinephrine; often used intentionally in refractory vasoplegic shock | Moderate |
| Guanethidine | Pharmacodynamic | Enhanced pressor response due to denervation supersensitivity | Major |
| Oxytocic agents (oxytocin, ergometrine) | Pharmacodynamic | Severe hypertension, stroke, and postpartum rupture of cerebral vessels reported | Major |
| Alpha-blockers (phentolamine, doxazosin) | Pharmacodynamic | Antagonism of vasopressor effect; useful therapeutically as antidote in extravasation | Major (dose escalation needed) |
| Non-selective beta-blockers (propranolol) | Pharmacodynamic | Unopposed alpha-adrenergic effect; risk of paradoxical hypertension and reflex bradycardia | Moderate |
Major Interactions
The most dangerous interactions involve drugs that significantly potentiate norepinephrine's cardiovascular effects. Halogenated volatile anesthetics are of particular concern in the operating room setting. These agents sensitize the myocardium to the arrhythmogenic effects of catecholamines, meaning that standard doses of norepinephrine can provoke life-threatening ventricular arrhythmias, including ventricular tachycardia and fibrillation, in patients under halogenated anesthesia. Dose reduction by 50–70% and enhanced cardiac rhythm monitoring are essential when these drugs must be combined. Where feasible, total intravenous anaesthesia (TIVA) techniques may be preferred in unstable patients.
MAO inhibitors represent a critical and potentially lethal interaction. Monoamine oxidase (MAO) is one of the two primary enzymes (alongside catechol-O-methyl transferase, COMT) responsible for terminating the action of norepinephrine. When MAO is inhibited, endogenous and exogenous norepinephrine accumulates dramatically, potentially causing hypertensive crisis with blood pressure elevations sufficient to produce intracranial hemorrhage, aortic dissection, or acute myocardial infarction. Patients receiving MAO inhibitors (including the reversible MAO-A inhibitor moclobemide, and the weak MAO inhibitor linezolid) require substantially reduced norepinephrine doses, often by 50–80%, and meticulous minute-to-minute blood pressure monitoring.
Tricyclic antidepressants (TCAs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) both inhibit the reuptake of norepinephrine at sympathetic nerve terminals, which is the primary mechanism by which norepinephrine is cleared from the synaptic cleft. When reuptake is blocked, the pressor effect of exogenous norepinephrine is dramatically enhanced and prolonged, necessitating careful dose titration and close hemodynamic monitoring. SNRIs such as venlafaxine and duloxetine are of particular concern because they are increasingly prescribed and may not be highlighted in hurried emergency medication reconciliations.
Moderate Interactions
Linezolid, an oxazolidinone antibiotic commonly prescribed in ICU patients for resistant gram-positive infections (including MRSA and VRE), has weak but clinically relevant MAO-inhibiting properties. While the interaction is less severe than with dedicated MAO inhibitors, it can still enhance norepinephrine's pressor effects, particularly at higher doses. Clinicians should be especially aware of this interaction since both drugs are frequently used together in critically ill patients with sepsis.
Methylene blue, traditionally used as an antidote for methemoglobinemia and more recently as rescue therapy in refractory vasodilatory (vasoplegic) shock, also inhibits MAO. When used concomitantly with norepinephrine, it can potentiate the pressor response. In practice, these drugs are sometimes used together intentionally in refractory shock, with careful dose titration and recognition that lower than usual norepinephrine doses may suffice.
Non-selective beta-blockers such as propranolol block norepinephrine's beta-1 cardiac effects (increased contractility and heart rate) while leaving alpha-1 vasoconstriction unopposed. This can produce exaggerated hypertension with reflex bradycardia and decreased cardiac output. Selective beta-1 blockers (metoprolol, bisoprolol, esmolol) are generally preferred if beta-blockade is clinically necessary during norepinephrine therapy.
Incompatibilities
Norepinephrine is chemically incompatible with alkaline solutions (including sodium bicarbonate and aminophylline), iron salts, oxidizing agents, and certain antibiotics (e.g., streptomycin). It should not be mixed in the same infusion line with barbiturates, phenytoin, or insulin. The product must be administered through a dedicated lumen of a multi-lumen central venous catheter wherever possible, with only compatible co-infusions running alongside. Contact with metal surfaces (other than stainless steel) can accelerate oxidative degradation.
What Is the Correct Dosage of Noradrenalin Laboratoire Aguettant?
Noradrenalin Laboratoire Aguettant 1 mg/ml is a concentrate that must be diluted before infusion. The typical initial dose in adults is 0.05–0.15 micrograms/kg/min, titrated to achieve a mean arterial pressure (MAP) of at least 65 mmHg. Maintenance doses typically range from 0.05 to 1.5 micrograms/kg/min, with individual patients occasionally requiring higher doses.
Dosing of norepinephrine is always individualized and depends on the patient's hemodynamic response, underlying diagnosis, concurrent therapies, and target blood pressure. The primary endpoint during septic shock resuscitation is typically a MAP of at least 65 mmHg, though higher targets (75–85 mmHg) may be appropriate in patients with chronic hypertension or known cerebrovascular disease, in accordance with the SEPSISPAM trial findings. All dose adjustments must be guided by continuous invasive blood pressure monitoring via an arterial line.
Dilution Instructions (1 mg/ml Concentrate)
Standard Dilution
To prepare the infusion from the 1 mg/ml concentrate, withdraw the required volume aseptically and add it to a compatible carrier fluid. Typical compatible fluids are 5% glucose (dextrose), 5% glucose with 0.9% sodium chloride, or 0.9% sodium chloride. Recommended final concentrations are 4 to 40 micrograms/ml (base), with lower concentrations for smaller infusion pumps and peripheral dilution logistics, and higher concentrations when fluid restriction is required. A common ICU standard is 8 mg in 250 ml (32 micrograms/ml base) or 16 mg in 250 ml (64 micrograms/ml base) for high-dose requirements.
Administration Equipment
The diluted solution must be delivered using a calibrated volumetric infusion pump or syringe pump capable of accurately delivering small hourly volumes. Delivery must be through a central venous catheter, preferably through a dedicated lumen. The infusion line should be clearly labelled with the drug name, concentration, and concentration units to prevent medication errors. Protect the infusion set from direct light where practical, although degradation within the 24-hour infusion window is generally minimal.
Adults
Initial Dose
The starting dose is typically 0.05–0.15 micrograms/kg/min (expressed as norepinephrine base). For a 70 kg adult this corresponds to approximately 3.5–10.5 micrograms/min. The infusion is initiated at the lower end of this range and titrated upward every few minutes based on the observed blood pressure response. Rapid dose escalation should be avoided when clinically feasible to allow for equilibration.
Maintenance Dose
The recommended maintenance dose range is 0.05–1.5 micrograms/kg/min. Once stable target blood pressure is achieved, the infusion should be maintained at the lowest effective rate. Doses exceeding 1 microgram/kg/min should prompt reassessment of the underlying cause of shock, adequacy of fluid resuscitation, and consideration of adjunctive therapies such as vasopressin (added at 0.03 units/min per SSC guidelines), hydrocortisone (if catecholamine-resistant), or advanced cardiovascular support.
Dose Titration
Once the infusion is established, the dose should be titrated in increments of 0.02–0.1 micrograms/kg/min based on the observed pressor effect. Each dose adjustment should be followed by a brief observation period (typically 3–5 minutes for small adjustments, 5–10 minutes for larger changes) to assess the hemodynamic response before making further changes. In refractory shock, titration may need to be more rapid under direct bedside supervision.
Weaning
Never discontinue norepinephrine abruptly. Once the patient demonstrates sustained hemodynamic stability, the infusion should be weaned by reducing the rate in small increments (typically 0.01–0.05 micrograms/kg/min every 15–30 minutes), with continuous monitoring for rebound hypotension. If MAP drops during weaning, the rate should be increased and the next weaning attempt delayed until the underlying cause is reassessed.
| Phase | Dose Range | Target | Notes |
|---|---|---|---|
| Initial dose | 0.05–0.15 mcg/kg/min | MAP ≥ 65 mmHg | Start low, titrate based on response |
| Maintenance | 0.05–1.5 mcg/kg/min | SBP 100–120 mmHg or MAP ≥ 65 mmHg | Use lowest effective dose |
| Titration increments | 0.02–0.1 mcg/kg/min per step | Gradual adjustment | Allow 3–10 min between adjustments |
| High-dose / refractory | > 1.0 mcg/kg/min | Add adjuncts | Consider vasopressin, hydrocortisone, reassess cause |
| Weaning | Gradual reduction (0.01–0.05 mcg/kg/min every 15–30 min) | Hemodynamic stability | Never stop abruptly; taper gradually |
Children
Noradrenalin Laboratoire Aguettant 1 mg/ml is not specifically licensed for paediatric use, though it is employed off-label in paediatric critical care. Paediatric dosing ranges vary by age and body weight but generally begin at 0.05–0.1 micrograms/kg/min in children and neonates. Paediatric dilutions are typically prepared at lower concentrations, often 0.04–0.4 mg/ml, and administered through a central venous catheter with continuous arterial line monitoring. All paediatric use should follow institutional protocols under the direction of paediatric intensivists or neonatologists.
Elderly Patients
No specific dose adjustment is recommended based on age alone. However, older adults commonly have reduced cardiovascular reserve, increased arterial stiffness, atherosclerotic vascular disease, and diminished baroreceptor sensitivity. In practice, clinicians typically initiate therapy at the lower end of the dosing range and titrate more slowly in elderly patients, with particular attention to signs of myocardial ischemia, peripheral vasoconstriction, and cerebral hypoperfusion. Comorbid coronary artery disease and heart failure may warrant the addition of an inotrope rather than isolated dose escalation.
Missed Dose
As norepinephrine is administered as a continuous intravenous infusion in a fully monitored critical care setting, the concept of a "missed dose" does not apply in the traditional outpatient sense. If the infusion is inadvertently interrupted (due to line disconnection, pump failure, or running out of the drug bag), blood pressure typically falls within minutes due to the short half-life. The infusion must be restarted as soon as possible, typically at the previous rate, with close monitoring as the patient may require temporary rate increases to recover MAP.
Overdose
Overdose with norepinephrine manifests as an exaggeration of its pharmacological effects. Clinical features include:
- Severe hypertension: Dangerously elevated blood pressure (systolic often > 200 mmHg) that can precipitate hemorrhagic stroke, intracranial hemorrhage, hypertensive encephalopathy, or aortic dissection
- Cutaneous vasoconstriction: Pronounced pallor, mottled skin, cold extremities, and prolonged capillary refill due to excessive peripheral vasoconstriction
- Pressure necrosis: Skin ulceration and digital gangrene resulting from prolonged severe vasoconstriction
- Reflex bradycardia: Significantly slow heart rate as a baroreceptor-mediated response to severe hypertension
- Paradoxical circulatory shock: Reduced cardiac output due to excessive afterload, myocardial ischemia, and secondary heart failure
- Pulmonary edema: Resulting from acute left ventricular dysfunction and increased systemic vascular resistance
- Acute kidney injury: Secondary to reduced renal perfusion and tissue hypoxia
Management of overdose involves immediate dose reduction or discontinuation, with supportive care including continuous hemodynamic monitoring, vasodilator therapy (phentolamine, an alpha-adrenergic blocker, or sodium nitroprusside for severe hypertension), and management of complications. The very short plasma half-life of norepinephrine (2–3 minutes) means that effects typically resolve rapidly after dose reduction. Treatment is primarily supportive; specific antidotes beyond alpha-adrenergic blockade are not required in most cases.
What Are the Side Effects of Noradrenalin Laboratoire Aguettant?
Like all medicines, norepinephrine can cause side effects, though not everyone will experience them. Cardiovascular effects predominate, including arrhythmias, tachycardia, bradycardia, and hypertension. Peripheral vasoconstriction can cause cold extremities and, with prolonged use, tissue hypoxia. Extravasation is a serious local complication that can cause tissue necrosis.
Side effects of norepinephrine are largely dose-dependent and mechanistic — that is, they reflect an exaggeration of the drug's intended vasoconstrictive and cardiac effects. Continuous hemodynamic monitoring allows for early detection and dose adjustment to minimize adverse effects while maintaining therapeutic benefit. Because the drug is used exclusively in the most critically ill patients, it can be difficult to distinguish drug-related adverse effects from the consequences of the underlying illness.
Cardiovascular Effects
- Arterial hypertension (may exceed target range)
- Tachycardia (rapid heart rate)
- Bradycardia (reflex, secondary to severe hypertension)
- Palpitations
- Increased myocardial contractility and myocardial oxygen demand
Peripheral Vascular Effects
- Cold and pale extremities, face, and digits
- Painful, cold, or numb hands and feet
- Prolonged capillary refill time
- Tissue hypoxia and elevated lactate (organ hypoperfusion)
- Mottled skin
Cardiac Arrhythmias
- Supraventricular tachycardia
- Atrial fibrillation
- Ventricular ectopy
- Ventricular tachycardia (rare, higher risk with halogenated anesthetics)
- Acute heart failure in susceptible patients
Neurological and Psychological
- Anxiety and restlessness (in conscious patients)
- Headache
- Tremor
- Sleep disturbance
Ocular
- Acute angle-closure glaucoma (increased intraocular pressure)
- Mydriasis (pupil dilation)
- Photophobia
Respiratory
- Dyspnoea (shortness of breath)
- Pulmonary edema (in severe overdose or cardiac dysfunction)
- Respiratory distress
Gastrointestinal, Renal, and Urinary
- Nausea and vomiting
- Reduced splanchnic (gut) perfusion
- Mesenteric ischemia (rare, high-dose)
- Reduced urine output (oliguria)
- Urinary retention
- Acute kidney injury with prolonged high-dose use
Local Effects (Infusion Site)
- Local irritation and phlebitis
- Tissue necrosis from extravasation
- Central line-associated bloodstream infection (CLABSI) with prolonged use
- Digital ischemia and, rarely, gangrene
Metabolic and Endocrine
- Hyperglycemia (glycogenolysis, insulin resistance)
- Metabolic acidosis (tissue hypoperfusion)
- Elevated serum lactate (marker of tissue hypoxia)
Hypersensitivity
- Hypersensitivity to norepinephrine or excipients (disodium edetate, sulfites in some formulations)
- Anaphylactoid reactions (extremely rare)
Effects of Prolonged Administration
Continuous administration of norepinephrine over several days to maintain blood pressure without adequate fluid volume replacement or correction of the underlying condition can lead to a cascade of detrimental effects. These include severe peripheral and visceral vasoconstriction (narrowing of blood vessels in extremities and internal organs including the gut and kidneys), reduced renal blood flow with potential acute kidney injury, decreased urine output (oliguria), tissue hypoxia, elevated serum lactate (a marker of anaerobic metabolism and inadequate tissue perfusion), digital ischemia with potential progression to gangrene in extreme cases, and worsening multi-organ dysfunction. These outcomes are more likely in patients requiring sustained high doses (> 1 microgram/kg/min) and underscore the importance of treating the underlying cause of shock rather than relying on escalating vasopressor therapy alone.
Hypersensitivity and Overdose-Related Effects
In patients with hypersensitivity to norepinephrine or in cases of overdose, additional symptoms may occur, including severe arterial hypertension, photophobia (abnormal light sensitivity), retrosternal pain (chest pain behind the breastbone), pharyngeal pain (sore throat), pronounced pallor, intense sweating, and vomiting. These symptoms require immediate dose reduction and appropriate supportive care, with alpha-blockade in severe cases. Allergic reactions, while very rare, should be considered if patients exhibit cutaneous flushing, wheezing, or cardiovascular collapse disproportionate to the expected hemodynamic response.
If you or someone you know experiences side effects during treatment with Noradrenalin Laboratoire Aguettant, these should be reported to the treating medical team immediately. Healthcare professionals can also report suspected adverse reactions to their national pharmacovigilance agency, such as the FDA MedWatch program (United States), the MHRA Yellow Card scheme (United Kingdom), the EMA EudraVigilance system (European Union), Health Canada's Canada Vigilance program, or Australia's TGA Pharmacovigilance. Reporting adverse reactions helps to monitor the benefit-risk profile of this medicinal product internationally.
How Should You Store Noradrenalin Laboratoire Aguettant?
Store Noradrenalin Laboratoire Aguettant 1 mg/ml at or below 25°C (77°F), protected from light in the original carton. Do not freeze. Use the contents immediately after opening. Discard any unused product. Do not use if the solution is darker than slightly yellow or pink, or if it contains visible particles.
Proper storage of norepinephrine is critical to maintaining its potency and safety profile. Norepinephrine is chemically unstable and undergoes oxidative degradation when exposed to light, elevated temperature, or alkaline pH. Its oxidation products (adrenochrome and related quinones) are pharmacologically inactive and may produce the characteristic yellow to pink-brown discoloration associated with deteriorated solutions. Degraded norepinephrine should never be administered because it is ineffective and may be potentially harmful.
- Temperature: Store at or below 25°C (77°F). Do not freeze. Avoid exposure to excessive heat or direct sunlight.
- Light protection: Keep the ampoules or vials in the original outer carton to protect from light. Norepinephrine is photosensitive and will degrade more rapidly when exposed to ambient light over time.
- After opening / dilution: Once the ampoule has been opened and the concentrate diluted, the infusion should be used immediately. From a microbiological perspective, the diluted solution should ideally be infused within 24 hours; any portion not used within this period should be discarded. Unused concentrate in opened ampoules must be discarded.
- Expiry date: Do not use after the expiry date (EXP) printed on the ampoule label and outer carton. The expiry date refers to the last day of the stated month.
- Visual inspection: Before use, visually inspect the solution. Do not use if the solution is darker than pale yellow or has developed a pink, brown, or amber discoloration, or if it contains visible particles, precipitates, or a damaged container seal.
- Packaging integrity: Do not use if the ampoule or vial shows signs of damage, cracks, or compromise of the sterile seal.
- Keep out of reach of children: As with all medications, store out of the sight and reach of children. In practice this medicinal product is used exclusively in hospital critical care settings.
Unused medication and pharmaceutical waste should be disposed of in accordance with local institutional guidelines and environmental regulations. Norepinephrine should not be disposed of via household waste or wastewater systems because of its potential environmental impact on aquatic ecosystems. Your hospital pharmacy and clinical waste service will provide the appropriate disposal route.
What Does Noradrenalin Laboratoire Aguettant Contain?
Each ml of Noradrenalin Laboratoire Aguettant 1 mg/ml concentrate contains 1 mg of norepinephrine (as norepinephrine tartrate, equivalent to approximately 2 mg norepinephrine tartrate). The solution also contains sodium chloride, disodium edetate, hydrochloric acid or sodium hydroxide for pH adjustment, and water for injections.
Active Ingredient
The active substance is norepinephrine (international nonproprietary name; also known as noradrenaline), present as norepinephrine tartrate. Each millilitre of the concentrate contains 1 mg of norepinephrine base, equivalent to approximately 2 mg of norepinephrine tartrate. Pack sizes commonly include 4 ml ampoules (4 mg norepinephrine base) and 8 ml ampoules (8 mg norepinephrine base), though not all pack sizes may be marketed in every country.
Excipients (Inactive Ingredients)
- Sodium chloride: Used as a tonicity agent to approximate the osmolality of the concentrate to physiological conditions following dilution
- Disodium edetate (EDTA): Used as a stabilizer and chelating agent to bind trace metal ions that would otherwise catalyse oxidative degradation of norepinephrine
- Hydrochloric acid and/or sodium hydroxide: Used for pH adjustment to a narrowly defined acidic pH range that maximises the chemical stability of norepinephrine in solution
- Water for injections: Pharmaceutical-grade water serving as the solvent
Physical Appearance
Noradrenalin Laboratoire Aguettant 1 mg/ml is a clear, colourless to slightly yellowish solution for infusion concentrate, presented in clear glass ampoules or vials. The product is supplied in packs of 10, 50, or 100 ampoules, though not all pack sizes may be marketed in every country or jurisdiction. Each ampoule is intended for single use only; any unused portion must be discarded.
Manufacturer and Marketing Authorization
The product is manufactured by Laboratoire Aguettant, located at 1, rue Alexander Fleming, 69007 Lyon, France. Laboratoire Aguettant is a French pharmaceutical company specializing in injectable medicines for hospital use, including other critical-care products such as lidokain-aguettant, midazolam-aguettant, bupivacaine-spinal-tung-aguettant, and the related 0.08 mg/ml ready-to-use noradrenalin formulation.
Compatibility with Infusion Fluids
Noradrenalin Laboratoire Aguettant 1 mg/ml concentrate is compatible for dilution with 5% glucose (dextrose), 5% glucose with 0.9% sodium chloride, or 0.9% sodium chloride. It is not compatible with alkaline solutions such as sodium bicarbonate, with solutions containing iron salts or other oxidizing agents, or with blood products. The diluted infusion must be administered through a dedicated line wherever possible; where co-infusion is unavoidable, only documented-compatible agents may be run through a shared lumen.
Frequently Asked Questions
Noradrenalin Laboratoire Aguettant 1 mg/ml is a concentrate for intravenous infusion used exclusively in hospital critical care settings for the emergency treatment of acute hypotension (dangerously low blood pressure). Its most common indication is septic shock, where it is recommended as the first-line vasopressor by the Surviving Sepsis Campaign 2021 guidelines. It is also used in cardiogenic shock, neurogenic shock, post-cardiac surgery vasoplegia, and refractory anaphylactic shock. It works by constricting blood vessels through alpha-1 adrenergic receptor stimulation, thereby raising mean arterial pressure and restoring tissue perfusion.
The 1 mg/ml concentrate must be diluted before administration. It is typically diluted in 5% glucose or 5% glucose with 0.9% sodium chloride to achieve a final concentration of 4 to 40 micrograms/ml (base), depending on the patient's fluid tolerance and required dose. A common ICU standard is 8 mg in 250 ml (32 micrograms/ml) or 16 mg in 250 ml (64 micrograms/ml) for high-dose requirements. It must be given as a continuous intravenous infusion through a central venous catheter using a calibrated infusion or syringe pump. It must never be given undiluted or through a peripheral IV line.
Both products contain norepinephrine tartrate and have identical pharmacology. The 1 mg/ml Noradrenalin Laboratoire Aguettant is a concentrate that must be diluted in a compatible infusion fluid before administration. The 0.08 mg/ml ready-to-use solution by the same manufacturer is pre-diluted and can be infused directly without further preparation. The concentrate offers flexibility in target infusion concentration based on patient fluid status and dose requirements. The ready-to-use formulation reduces the risk of medication errors associated with manual dilution and is faster to initiate in time-critical emergencies. Institutional preference and patient-specific factors determine which formulation is used.
Norepinephrine (noradrenaline) and epinephrine (adrenaline) are both catecholamines but act differently on adrenergic receptors. Norepinephrine primarily stimulates alpha-1 receptors, producing intense vasoconstriction with moderate beta-1 cardiac stimulation, making it ideal for raising blood pressure in septic shock and other distributive shock states. Epinephrine acts more equally on both alpha and beta receptors, producing stronger heart rate and contractility increases, making it the drug of choice for anaphylaxis and cardiac arrest. Norepinephrine causes less tachycardia and less hyperlactataemia than equipotent doses of epinephrine in septic shock.
The most frequently reported side effects of norepinephrine include cardiovascular effects such as tachycardia, bradycardia, cardiac arrhythmias (including atrial fibrillation and ventricular ectopy), and excessive hypertension. Peripheral vascular effects are also common, including cold pale extremities, reduced blood flow to fingers and toes, mottled skin, and elevated lactate. Neurological effects such as anxiety, headache, and tremor may also occur in conscious patients. Most side effects are dose-dependent and can be managed by dose adjustment. The most serious local complication is tissue necrosis from extravasation.
No, norepinephrine must never be stopped abruptly. Sudden discontinuation can cause acute, life-threatening rebound hypotension because the underlying vasodilation or myocardial depression that prompted the infusion is typically still present. The infusion must always be tapered gradually, with dose reductions made in small increments (typically 0.01–0.05 micrograms/kg/min every 15–30 minutes) while monitoring blood pressure and MAP closely. When the patient is ready for weaning, the dose is progressively reduced until hemodynamic stability is maintained without vasopressor support. If blood pressure falls during weaning, the rate should be increased and the next weaning attempt delayed.
Norepinephrine must be given through a central venous catheter because of the severe risk of tissue damage if the drug leaks out of a peripheral vein (extravasation). Norepinephrine causes intense vasoconstriction, and if it escapes into the surrounding subcutaneous tissue, it can cut off blood supply to the skin and underlying structures, leading to tissue ischemia, full-thickness necrosis, and in severe cases requiring surgical debridement, skin grafting, or even amputation of affected digits. Central venous catheters sit in large-diameter high-flow veins (typically the superior vena cava), which dilute the drug rapidly and dramatically reduce the risk of local tissue injury should minor extravasation occur.
References
- Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2021. Intensive Care Medicine. 2021;47(11):1181-1247. doi:10.1007/s00134-021-06506-y
- De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. New England Journal of Medicine. 2010;362(9):779-789. doi:10.1056/NEJMoa0907118
- Asfar P, Meziani F, Hamel JF, et al. High versus low blood-pressure target in patients with septic shock (SEPSISPAM). New England Journal of Medicine. 2014;370(17):1583-1593. doi:10.1056/NEJMoa1312173
- European Medicines Agency (EMA). Summary of Product Characteristics: Norepinephrine tartrate 1 mg/ml concentrate for solution for infusion. EMA product database. Accessed 2026.
- Overgaard CB, Dzavik V. Inotropes and vasopressors: review of physiology and clinical use in cardiovascular disease. Circulation. 2008;118(10):1047-1056. doi:10.1161/CIRCULATIONAHA.107.728840
- World Health Organization (WHO). WHO Model List of Essential Medicines - 23rd List, 2023. Geneva: World Health Organization; 2023.
- British National Formulary (BNF). Noradrenaline (norepinephrine) — monograph. NICE Evidence Services. Updated 2026.
- Annane D, Ouanes-Besbes L, de Backer D, et al. A global perspective on vasoactive agents in shock. Intensive Care Medicine. 2018;44(6):833-846. doi:10.1007/s00134-018-5242-5
- Russell JA, Walley KR, Singer J, et al. Vasopressin versus norepinephrine infusion in patients with septic shock (VASST). New England Journal of Medicine. 2008;358(9):877-887. doi:10.1056/NEJMoa067373
- Laboratoire Aguettant. Noradrenalin Laboratoire Aguettant 1 mg/ml, concentrate for solution for infusion — Summary of Product Characteristics. Lyon, France. Last updated 2025.
- Vincent JL, De Backer D. Circulatory shock. New England Journal of Medicine. 2013;369(18):1726-1734. doi:10.1056/NEJMra1208943
- Hollenberg SM. Vasoactive drugs in circulatory shock. American Journal of Respiratory and Critical Care Medicine. 2011;183(7):847-855. doi:10.1164/rccm.201006-0972CI
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