Patient leaflets and SmPCs, drug interaction checker, official and paediatric dosages, pregnancy and breastfeeding guidance, and NHS pharmacy opening hours — all in one place.
Patient leaflets and SmPCs, drug interaction checker, official and paediatric dosages, pregnancy and breastfeeding guidance, and NHS pharmacy opening hours — all in one place.
Noradrenaline (Norepinephrine) 1 mg/ml concentrate for solution for infusion contains the active substance noradrenaline and act as a vasoconstrictor (causes narrowing of blood vessels). Noradrenaline is used in adults in an emergency to increase blood pressure to normal levels.
You should not be given Noradrenaline • if you are allergic to noradrenaline or any of the other ingredients of this medicine (listed in section 6) • if you have low blood pressure that has been caused by low blood volume • if you receive some anaesthetics such as halothane or cyclopropane (this may increase the risk of irregular heart beat).
Warnings and precautions Talk to your doctor or nurse before you are given noradrenaline if you: • have diabetes • have liver failure • have severe kidney disorders • suffer from high blood pressure • have an over-active thyroid gland • have low levels of oxygen in the blood • have high levels of carbon dioxide in the blood • have elevated pressure inside the skull (intracranial pressure) • have clots or obstructions in the blood vessels supplying the heart, intestines, or other parts of the body • have low blood pressure following a heart attack • have a type of angina (chest pain) called Prinzmetal's angina • have major left ventricular dysfunction (a heart condition) • have recently had myocardial infarction • have cardiac rhythm disorders (your heart beats too fast, too slow or irregular), you will need a reduced dose • are elderly
Children and adolescents The safety and efficacy of noradrenaline in children less than 18 years of age has not been established. Therefore use in children is not recommended.
Other medicines and Noradrenaline Tell your doctor or nurse if you are using, have recently used or might use any other medicines. It is particularly important if you use or have recently used any of the following medicines: • medicines to treat depression called 'monoamine oxidase inhibitors' that are currently being taken or have been taken in the last 14 days • medicines to treat depression called 'tricyclic antidepressants' e.g. imipramine or desipramine • adrenergic-serotoninergic medicines, e.g. used in the treatment of asthma and heart conditions • linezolid (an antibiotic) • anaesthetics (especially anaesthetic gases such as cyclopropane, halothane, chloroform, enflurane) • medicines to treat high blood pressure (e.g. guanethidine, reserpine, methyldopa, alpha and beta-blockers) • medicines to treat heart rhythm disorders • cardiac glycosides (to treat heart diseases) • levodopa (to treat Parkinson's disease) • thyroid hormones • oxytocin (used to improve uterine contractions) • antihistamines (for treating allergies) • amphetamine • doxapram (for breathing disorders)
The following information is intended for healthcare professionals only:
Method of administration Intravenous use after dilution. Administer as a diluted solution via a central venous catheter. The infusion should be at a controlled rate using either a syringe pump or an infusion pump or a drip counter. Do not use undiluted.
Incompatibilities Infusion solutions containing noradrenaline tartrate have been reported to be incompatible with the following substances: iron salts, alkalis and oxidising agents, barbiturates, chlorpheniramine, chlorothiazide, nitrofurantoin, novobiocin, phenytoin, sodium bicarbonate, sodium iodide, streptomycin, sulfadiazine, sulfafurazole. This medicinal product must not be mixed with other medicinal products except those mentioned below.
Dilution instructions
For single use only. Discard any unused contents.
The solution should be visually inspected prior to use. The medicine should not be used if the solution
Package leaflet: information for the user
• mazindol (to treat obesity) • medicines to treat migraine (ergot alkaloids) • lithium (to treat some mental disorders)
Using noradrenaline with propofol (an anaesthetic) may lead to propofol infusion syndrome (PRIS), which is a serious condition that affects patients who are being sedated with propofol in intensive care units. Your doctor would notice disorders in your body's metabolism from blood tests and this could lead to kidney failure, heart failure and death.
Pregnancy and breast-feeding If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before this medicine is given to you. Noradrenaline may harm the unborn baby. Your doctor will decide if you should be given noradrenaline. It is not known whether this medicine is excreted in human milk. Because many medicines are excreted in human milk, caution should be exercised when noradrenaline is given to a nursing woman.
Driving and using machines No information is available. Therefore, driving or operating machinery is not recommended.
Noradrenaline contains sodium Ampoules containing 1 ml, 2 ml, 4 ml or 5 ml of concentrate for solution for infusion contains less than 1 mmol sodium (23 mg) per ampoule, that is to say essentially 'sodium-free'.
Each ampoule containing 8 ml of concentrate for solution for infusion contains 26.4 mg sodium (main component of cooking/table salt). This is equivalent to 1.32 % of the recommended maximum daily dietary intake of sodium for an adult.
Each ampoule containing 10 ml of concentrate for solution for infusion contains 33 mg sodium (main component of cooking/table salt). This is equivalent to 1.65 % of the recommended maximum daily dietary intake of sodium for an adult.
How Noradrenaline will be given
Noradrenaline will be given to you in hospital by a doctor or nurse. It is first diluted and then infused into a vein.
The initial dose of noradrenaline will depend on your medical condition. The usual dose is between 0.4 mg and 0.8 mg noradrenaline per hour. Your doctor will determine the correct dose for you. After the initial dose your doctor will assess your response and adjust the dose accordingly.
Your doctor will monitor your blood pressure and blood volume.
If you are given more Noradrenaline than you should It is unlikely that you will receive too much as this medicine will be given to you in hospital. However, talk to your doctor or nurse if you have any concerns. Symptoms that may occur if you are given too much noradrenaline are severe high blood pressure, slow heartbeat, violent headache, light sensitivity, pain in the chest, bleeding in the brain, pallor, fever, intense sweating and vomiting, fluid in the lungs causing breathlessness.
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor or nurse immediately if you experience: • sudden itchy rash (hives), swelling of the hands, feet, ankles, face, lips, mouth or throat (which may cause difficulty in swallowing or breathing), feeling that you are going to faint • pain and/or swelling at the injection site.
Tell your doctor or nurse as soon as possible if you experience: • anxiety, insomnia, confusion, weakness, psychotic state • headaches, tremor • decreased or increased heart rate • abnormal heart rhythm • electrocardiogram change
contains visible particles/solids. Do not use the solution for infusion if it has a brown colour.
Dilute before use with: ‒ glucose 50 mg/ml (5%) solution or ‒ sodium chloride 9 mg/ml (0.9%) solution or ‒ sodium chloride 9 mg/ml (0.9%) with glucose
50 mg/ml (5%) solution.
Either add 2 ml concentrate to 48 ml glucose 50 mg/ml (5%) solution (or any of the other above mentioned solutions for dilution) for administration by syringe pump, or add 20 ml of concentrate to 480 ml glucose 50 mg/ml (5%) solution (or any of the other above mentioned solutions for dilution) for administration by drip counter. In both cases the final concentration of the infusion solution is 40 mg/litre noradrenaline (which is equivalent to 80 mg/litre noradrenaline tartrate). Dilutions other than 40 mg/litre noradrenaline may also be used. If dilutions other than 40 mg/litre noradrenaline are used, check the infusion rate calculation carefully before starting treatment.
The product is compatible with polyvinyl chloride (PVC), ethyl vinyl acetate (EVA) or polyethylene (PE) infusion bags.
• a potentially life-threatening type of circulatory failure called 'cardiogenic shock' • heart muscle weakness due to intense physical or emotional stress, palpitations, increase in the contractility of the heart muscle • high blood pressure, decrease in oxygen supply to some organ (hypoxia) • poor blood flow to your hands and feet (may cause coldness, paleness and/or pain in the limbs) • gangrene (tissue death) • reduction in blood plasma volume • breathing difficulties • paleness, scarification of the skin, bluish skin colour, hot flushes or skin redness, skin rash, hives or itching • nausea, vomiting • retention of urine • irritation or ulceration at the injection site
In case of hypersensitivity or overdose, the following effects may appear more frequently: very high blood pressure, abnormal sensitivity to or intolerance of light, pain behind the breast bone, pharyngeal pain, pallor, intense sweating and vomiting.
Reporting of side effects If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. By reporting side effects, you can help provide more information on the safety of this medicine.
Keep this medicine out of the sight and reach of children.
Do not store above 25 °C. Keep the ampoules in the outer carton in order to protect from light.
Shelf life after opening the ampoule Once opened, the diluted solution should be prepared immediately.
Shelf life after dilution Chemical and physical in-use stability has been demonstrated for 48 hours at 25 °C and 2-8 °C when diluted to 4 mg/litre and 40 mg/litre noradrenaline in sodium chloride 9 mg/ml (0.9%) solution or glucose 50 mg/ml (5%) solution, or sodium chloride 9 mg/ml (0.9%) with glucose 50 mg/ml (5%) solution. From a microbiological point of view, the diluted solution should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8 °C, unless dilution has taken place in controlled and validated aseptic conditions.
Do not use this medicine after the expiry date which is stated on the carton and ampoule label after EXP. The expiry date refers to the last day of that month.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
What Noradrenaline contains ‒ The active substance is noradrenaline.
Each 1 ml of concentrate for solution for infusion contains noradrenaline tartrate equivalent to 1 mg noradrenaline. Each ampoule containing 2 ml of concentrate for solution for infusion contains noradrenaline tartrate equivalent to 2 mg noradrenaline. Each ampoule containing 4 ml of concentrate for solution for infusion contains noradrenaline tartrate equivalent to 4 mg noradrenaline. Each ampoule containing 5 ml of concentrate for solution for infusion contains noradrenaline tartrate equivalent to 5 mg noradrenaline. Each ampoule containing 8 ml of concentrate for solution for infusion contains noradrenaline tartrate equivalent to 8 mg noradrenaline. Each ampoule containing 10 ml of concentrate for solution for infusion contains noradrenaline tartrate equivalent to 10 mg noradrenaline.
‒ The other ingredients are sodium chloride, hydrochloric acid (for pH adjustment), water for injections.
Instruction of ampoule opening 1) Turn the ampoule with coloured point up. If there is any solution in the upper part of the ampoule, gently tap with your finger to get all the solution to the lower part of the ampoule. 2) Use both hands to open; while holding the lower part of the ampoule in one hand, use the other hand to break off the upper part of the ampoule in the direction away from the coloured point (see the pictures below).
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
What Noradrenaline looks like and contents of the pack Clear, colourless or yellowish solution, practically free from visible particles.
1 ml, 2 ml, 4 ml, 5 ml, 8 ml or 10 ml of solution filled in colourless glass ampoules with one point cut. The ampoules are packed in a liner and placed into carton box.
Pack sizes: 5 or 10 ampoules
Not all pack sizes may be marketed.
Marketing authorisation holder and Manufacturer AS KALCEKS Krustpils iela 71E, Rīga, LV-1057, Latvia Tel.: +371 67083320 E-mail: [email protected]
This medicine is authorised in the Member States of the European Economic Area and in the United Kingdom (Northern Ireland) under the following names: Denmark Noradrenalin Kalceks Austria Norepinephrin Kalceks 1 mg/ml Konzentrat zur Herstellung einer Infusionslösung Belgium Noradrenaline (Norepinephrine) Kalceks 1 mg/ml concentraat voor oplossing voor infusie / solution à diluer pour perfusion / Konzentrat zur Herstellung einer Infusionslösung Czech Republic Norepinephrine Kalceks Estonia Norepinephrine Kalceks Finland Noradrenalin Kalceks France NORADRENALINE TARTRATE KALCEKS 1 mg/mL, solution à diluer pour perfusion Germany Norepinephrin Kalceks 1 mg/ml Konzentrat zur Herstellung einer Infusionslösung Hungary Norepinephrine Kalceks 1 mg/ml koncentrátum oldatos infúzióhoz Ireland Noradrenaline (Norepinephrine) 1 mg/ml concentrate for solution for infusion Italy Norepinefrina Kalceks Latvia Norepinephrine Kalceks 1 mg/ml koncentrāts infūziju šķīduma pagatavošanai Lithuania Norepinephrine Kalceks 1 mg/ml koncentratas infuziniam tirpalui Norway Noradrenalin Kalceks Poland Noradrenalin Kalceks Portugal Noradrenalina Kalceks Romania Noradrenalină Kalceks 1 mg/ml concentrat pentru soluţie perfuzabilă Slovakia Norepinephrine Kalceks 1 mg/ml infúzny koncentrát Spain Noradrenalina Kalceks 1 mg/ml concentrado para solución para perfusión EFG Sweden Noradrenalin Kalceks The Netherlands Noradrenaline Kalceks 1 mg/ml
concentraat voor oplossing voor infusie United Kingdom (Northern Ireland)
Noradrenaline (Norepinephrine) 1 mg/ml concentrate for solution for infusion
This leaflet was last revised in 05/2024
Noradrenaline (Norepinephrine) 1 mg/ml concentrate for solution for infusion comes as infusion containing 1mg/ml. Always follow the dose your doctor or pharmacist has given you, and read the leaflet that comes with the medicine.
The active substance in Noradrenaline (Norepinephrine) 1 mg/ml concentrate for solution for infusion is noradrenaline.
Medicines with the same active substance, strength and form include: Noradrenaline (Norepinephrine) 1 mg/ml Concentrate for Solution for Infusion, Noradrenaline (Norepinephrine) 1 mg/ml Concentrate for Solution for Infusion. They are interchangeable only if your prescriber or pharmacist says so.
This leaflet reproduces the patient information leaflet approved for Noradrenaline (Norepinephrine) 1 mg/ml concentrate for solution for infusion, as published on the electronic medicines compendium (emc). The version printed inside your medicine’s packaging is the one that applies to you.
Whether a medicine is available over the counter or on prescription only depends on its licence. Check the leaflet, or ask your pharmacist — they can tell you straight away.
The text above reproduces the patient information leaflet approved for this medicine, restructured for easier reading.
Noradrenaline (Norepinephrine) 1 mg/ml concentrate for solution for infusion is recommended in adults for use as an emergency measure in the restoration of blood pressure in cases of acute hypotension.
Posology
Adults
Add 2 ml of Noradrenaline (Norepinephrine) 1 mg/ml concentrate for solution for infusion to 48 ml 50 mg/ml (5%) glucose (or other in section 6.6 mentioned solutions for dilution) for administration by syringe pump. The final concentration of the infusion solution is 80 mg/litre noradrenaline (norepinephrine) tartrate, which is equivalent to 40 mg/litre noradrenaline. If other dilutions are used check the calculation carefully before starting treatment.
Initial rate of infusion
The initial rate of infusion should be between 10 ml/hour and 20 ml/hour (0.16 ml/min to 0.32 ml/min). This is equivalent to 0.8 mg/hour to 1.6 mg/hour noradrenaline (norepinephrine) tartrate (or 0.4 mg/hour to 0.8 mg/hour noradrenaline).
Titration of dose
Once an infusion of noradrenaline has been established the dose should be titrated according to the pressor effect observed. There is great individual variation in the dose required to attain and maintain normotension. The aim should be to establish a low normal systolic blood pressure (100-120 mm Hg) or to achieve an adequate mean arterial blood pressure (greater than 65-80 mm Hg – depending on the patient's condition).
Table 1 Dose titration of noradrenaline solution for infusion
Noradrenaline infusion solution
40 mg/litre (40 µg/ml) noradrenaline
Patient's weight
Posology
(µg/kg/min)
noradrenaline
Posology
(mg/hour)
noradrenaline
Infusion rate
(ml/hour)
40 kg
0.05
0.12
3.0
0.1
0.24
6.0
0.25
0.60
15.0
0.5
1.2
30.0
1
2.4
60
50 kg
0.05
0.15
3.75
0.1
0.3
7.5
0.25
0.75
18.75
0.5
1.5
37.5
1
3
75
60 kg
0.05
0.18
4.5
0.1
0.36
9
0.25
0.9
22.5
0.5
1.8
45
1
3.6
90
70 kg
0.05
0.21
5.25
0.1
0.42
10.5
0.25
1.05
26.25
0.5
2.1
52.5
1
4.2
105
80 kg
0.05
0.24
6
0.1
0.48
12
0.25
1.2
30
0.5
2.4
60
1
4.8
120
90 kg
0.05
0.27
6.75
0.1
0.54
13.5
0.25
1.35
33.75
0.5
2.7
67.5
1
5.4
135
Duration of treatment and monitoring
Noradrenaline should be continued until adequate blood pressure and tissue perfusion are maintained without therapy. The patient should be monitored carefully for the duration of noradrenaline therapy.
Noradrenaline should only be administered by healthcare professionals who are familiar with its use and have appropriate facilities to adequately monitor the patient.
Withdrawal of therapy
Infusions should be reduced gradually, avoiding abrupt withdrawal which can result in acute hypotension.
Hepatic/renal impairment
There is no experience in treatment of hepatically or renally impaired patients.
Elderly
In general, dose selection for an elderly patient should be cautious, starting at the low end of the dosing range as to reflect the greater frequency of decreased hepatic, renal or cardiac function and concomitant disease or other drug therapy.
Paediatric population
The safety and efficacy of noradrenaline in children less than 18 years of age has not yet been established. No data are available.
Method of administration
Route of administration
Intravenous use after dilution.
Noradrenaline (Norepinephrine) 1 mg/ml concentrate for solution for infusion should be diluted and should be administered via a central venous catheter. The infusion should be at a controlled rate using either a syringe pump or an infusion pump or a drip counter.
For instructions on dilution of the medicinal product before administration, see section 6.6.
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Hypotension due to blood volume deficit (hypovolaemia).
Do not use with cyclopropane and halothane anaesthetics. For interactions see section 4.5.
The use of pressor amines during cyclopropane or halothane anaesthesia may cause serious cardiac arrhythmias. Because of the possibility of increasing the risk of ventricular fibrillation, noradrenaline should be used with caution in patients receiving these or any other cardiac sensitising agent or who exhibit profound hypoxia or hypercarbia.
The administration in the veins of the lower limbs of the elderly and patients with occlusive diseases due to possible vasoconstriction should be avoided (see section 4.4).
Do not use undiluted.
Noradrenaline should not be given to patients who are hypotensive from blood volume deficits except as an emergency measure to maintain coronary and cerebral artery perfusion until blood volume replacement therapy can be completed.
Noradrenaline should be used only in conjunction with appropriate blood volume replacement.
If noradrenaline is continuously administered to maintain blood pressure in the absence of blood volume replacement, the following may occur: severe peripheral and visceral vasoconstriction, decreased renal perfusion and urine output, poor systemic blood flow despite “normal” blood pressure, tissue hypoxia and lactic acidosis. Blood volume replacement can be administered before and/or concurrently with this agent; however, if whole blood or blood plasma is indicated to increase blood volume, administer separately (e.g. if given simultaneously, use Y-tubing and individual containers).
Prolonged administration of any potent vasopressor may result in plasma volume depletion which should be continuously corrected by appropriate fluid and electrolyte replacement therapy. If plasma volumes are not corrected, hypotension may recur when noradrenaline is discontinued or the blood pressure may be maintained at the risk of severe peripheral and visceral vasoconstriction (e.g. decreased renal perfusion) with diminution in blood flow and tissue perfusion with subsequent tissue hypoxia and lactic acidosis and possible ischemic injury; gangrene of extremities has been rarely reported.
When infusing noradrenaline, the blood pressure and rate of flow should be checked frequently to avoid hypertension, which may be associated with bradycardia as well as headache and peripheral ischemia, including rarely gangrene of the extremities. Extravasation may cause local tissue necrosis (see section 'Extravasation' below).
Caution is advised in patients with major left ventricular dysfunction associated with acute hypotension. Supportive therapy should be initiated simultaneously with diagnostic evaluation. Noradrenaline should be reserved for patients with cardiogenic shock and refractory hypotension, in particular those without elevated systemic vascular resistance.
Occurrence of heart rhythm disorders during the treatment must lead to a reduction in the dosage.
Cardiac arrhythmias may arise when noradrenaline is used in conjunction with cardiac sensitizing agents, and may be more likely in patients with hypoxia or hypercarbia.
Particular caution should be observed in patients with coronary, mesenteric or peripheral vascular thrombosis because noradrenaline may increase the ischemia and extend the area of infarction, unless in the opinion of the attending physician, the administration of noradrenaline is necessary as a life-saving procedure. Similar caution should be observed in patients with hypotension following myocardial infarction and in patients with angina, particularly Prinzmetal's variant angina, diabetes, hypertension or hyperthyroidism (see section 4.8).
Special caution should be used for patients with liver failure, severe renal dysfunction, ischemic heart diseases and elevated intracranial pressure. Overdoses or conventional doses in hypersensitive persons (e.g. hyperthyroid patients) may cause severe hypertension with violent headache, photophobia, stabbing retrosternal pain, pallor, intense sweating and vomiting. Hypertension may eventually lead to acute pulmonary oedema, arrhythmia or cardiac arrest.
Care should be taken in diabetics as it increases the level of blood glucose (due to the glycogenolytic action in the liver and the inhibition of insulin release from the pancreas).
The elderly may be especially sensitive to the effects of noradrenaline due to the greater frequency of hepatic, renal or cardiac dysfunction and concomitant disease or other drug therapy.
The use of noradrenaline in children is not recommended (see sections 4.2 and 5.2).
Noradrenaline should only be used by doctors familiar with the selective indications for its use.
Where indicated, appropriate replacement therapy of blood or fluid together with adoption of the supine position with elevation of the legs, must be instituted and maintained prior to and/or during therapy with this product. When infusing noradrenaline, the blood pressure and rate of flow should be checked frequently to avoid hypertension. Therefore, it is desirable to record the blood pressure every two minutes from the time the administration started until the desired blood pressure is obtained and then every five minutes thereafter, if the administration is to be continued. The rate of flow must be watched constantly and the patient should never be left unattended while receiving noradrenaline. Hypertension may eventually lead to acute pulmonary oedema, arrhythmia or cardiac arrest.
The infusion of noradrenaline should be stopped gradually as sudden cessation may produce a catastrophic fall in blood pressure.
Extravasation
The infusion site should be checked frequently for free flow. Care should be taken to avoid extravasation of noradrenaline into the tissues, as local necrosis might ensue due to the vasoconstrictive action of the drug. Blanching along the course of the infused vein, sometimes without obvious extravasation, has been attributed to vasa vasorum constriction with increased permeability of the vein wall, permitting some leakage. On rare occasions this may progress to superficial slough, particularly during infusion into leg veins in elderly patients or in those suffering from obliterative vascular disease. If blanching occurs, consideration should be given to changing the infusion site at intervals to allow the effects of local vasoconstriction to subside.
IMPORTANT – Antidote for extravasation ischaemia
To prevent sloughing and necrosis in areas in which extravasation has taken place, the area should be infiltrated as soon as possible with 10 ml to 15 ml of saline solution containing from 5 mg to 10 mg of phentolamine, an adrenergic blocking agent. A syringe with a fine hypodermic needle should be used with the solution being infiltrated liberally throughout the area, which is easily identified by its cold, hard and pallid appearance. Sympathetic blockade with phentolamine causes immediate and conspicuous local hyperaemic changes if the area is infiltrated within 12 hours. Phentolamine should be given as soon as possible after the extravasation is noted and infusion should be stopped.
Excipients
Ampoules containing 1 ml, 2 ml, 4 ml or 5 ml of concentrate for solution for infusion contains less than 1 mmol sodium (23 mg) per ampoule, that is to say essentially 'sodium-free'.
Each ampoule containing 8 ml of concentrate for solution for infusion contains 26.4 mg (1.12 mmol) sodium, equivalent to 1.32 % of the WHO recommended maximum daily intake of 2 g sodium for an adult.
Each ampoule containing 10 ml of concentrate for solution for infusion contains 33 mg (1.40 mmol) sodium, equivalent to 1.65 % of the WHO recommended maximum daily intake of 2 g sodium for an adult.
Inadvisable combinations
- Volatile halogenated anaesthetics: severe ventricular arrhythmia (increase in cardiac excitability).
- Imipramine antidepressants: paroxysmal hypertension with the possibility of arrhythmia (inhibition of the entry of sympathomimetics into sympathetic fibres).
- Serotoninergic-adrenergic antidepressants: paroxysmal hypertension with the possibility of arrhythmia (inhibition of the entry of sympathomimetics into sympathetic fibres).
- Digitalis glycosides.
- Levodopa.
- Chlorpheniramine hydrochloride, tripelennamine hydrochloride and desipramine: significantly increase the toxicity of noradrenaline.
- Antihistamines, as some may block the intake of catecholamines by peripheral tissues and increase the toxicity of injected noradrenaline.
The use of pressor amines with cyclopropane, halothane, chloroform, enflurane or other halogenated anaesthetics may cause serious cardiac arrhythmias, because of the possibility of increasing the risk of ventricular fibrillation, noradrenaline should be used with caution in patients receiving these or any other cardiac sensitising agent or who exhibit profound hypoxia or hypercarbia.
Combinations requiring precautions for use
- Non-selective monoamine oxidase (MAO) inhibitors: increase in the pressor action of the sympathomimetic which is usually moderate. Should only be used under close medical supervision.
- Selective MAO-A inhibitors: by extrapolation from non-selective MAO inhibitors, risk of increase in the pressor action. Should only be used under close medical supervision.
- Linezolid: by extrapolation from non-selective MAO inhibitors: risk of increase in the pressor action. Should only be used under close medical supervision.
Noradrenaline should be used with extreme caution in patients receiving MAO inhibitors or within 14 days of cessation of such therapy.
The effects of noradrenaline may be enhanced by guanethidine, guanadrel, reserpine, methyldopa or tricyclic antidepressants, amphetamine, doxapram, mazindol, rauwolfia alkaloids.
Caution is required when using noradrenaline with alpha and beta blockers as severe hypertension may result.
Caution is required when using noradrenaline with the following drugs as they may cause increased cardiac effects: thyroid hormones, cardiac glycosides, antiarrhythmic.
Ergot alkaloids (ergoloid mesylates, ergotamine, dihydroergotamine, ergometrine, methylergometrine, and methysergide) or oxytocin may enhance the vasopressor and vasoconstrictive effects.
Concomitant administration of propofol and noradrenaline may lead to propofol infusion syndrome (PRIS).
Desmopressin or vasopressin: its antidiuretic effect is diminished.
Lithium decreases the effect of noradrenaline.
Noradrenaline infusion solutions should not be mixed with other medications (except those mentioned in section 6.6).
Pregnancy
Noradrenaline may impair placental perfusion and induce foetal bradycardia. It may also exert a contractile effect on the pregnant uterus and lead to foetal asphyxia in late pregnancy. These possible risks to the foetus should therefore be weighed against the potential benefit to the mother.
Breast-feeding
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when noradrenaline is administered to a nursing woman.
Fertility
No studies have been performed to collect fertility data for noradrenaline.
No information is available. Therefore, driving or operating machinery is not recommended.
Table 2 lists adverse reactions that have been experienced following treatment with noradrenaline. This data has largely been collected from spontaneous reporting, and due to the problems in calculating reporting frequencies from spontaneous reporting, the frequency of the listed adverse reactions is 'not known' (cannot be estimated from the available data). The adverse reactions are reported in decreasing order of frequency within each system order class (SOC).
Table 2 Adverse reactions reported with noradrenaline through spontaneous reporting
System Organ Class (SOC)
Adverse Reactions
Psychiatric disorders
Anxiety, insomnia, confusion, weakness, psychotic state
Nervous system disorders
Transient headache, tremor
Cardiac disorders
Bradycardia1, arrhythmia, electrocardiogram change, tachycardia, cardiogenic shock, stress cardiomyopathy, palpitations, increase in the contractility of the cardiac muscle resulting from the beta-adrenergic effect on the heart (inotrope and chronotrope)
Vascular disorders
Hypertension, peripheral ischaemia2 including gangrene of the extremities, plasma volume depletion with prolonged use, ischaemic injury due to potent vasoconstrictor action may result in coldness and paleness of the limbs
Gastrointestinal disorders
Nausea, vomiting
Skin and subcutaneous tissue disorders
Paleness, scarification of the skin, bluish skin colour, hot flushes or skin redness, skin rash, hives or itching
Renal and urinary disorders
Retention of urine
Respiratory, thoracic and mediastinal disorders
Dyspnoea
General disorders and administration site conditions
Extravasation, injection site necrosis
1 Bradycardia, probably as a reflex result of a rise in blood pressure
2 Ischaemia, due to potent vasoconstrictor action and tissue hypoxia
The continuous administration of vasopressor to maintain blood pressure in absence of blood volume replacement may cause the following symptoms:
- severe peripheral and visceral vasoconstriction
- decrease in renal blood flow
- decrease in urine production
- hypoxia
- increase in lactate serum levels.
In case of hypersensitivity or overdose, the following effects may appear more frequently: hypertension, photophobia, retrosternal pain, pharyngeal pain, pallor, intense sweating and vomiting.
The vasopressor effect (resulting from the adrenergic action on the vessels) can be reduced by the concomitant administration of an alpha blocking agent (phentolamine mesilate) whereas the administration of a beta blocking agent (propranolol) may result in a reduction of the stimulating effect of the product on the heart and in an increase of the hypertensor effect (through reduction of arteriolar dilatation), resulting from beta-1 adrenergic stimulation.
Prolonged administration of any potent vasopressor may result in plasma volume depletion which should be continuously corrected by appropriate water and electrolyte replacement therapy. If plasma volumes are not corrected, hypotension may recur when the noradrenaline infusion is discontinued, or blood pressure may be maintained with the risk of severe peripheral and visceral vasoconstriction with diminution in blood flow.
Hypertension may occur, which may be associated with bradycardia as well as headache and peripheral ischemia, including gangrene of the extremities.
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: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Symptoms
Overdosage may result in headache, severe hypertension, reflex bradycardia, marked increase in peripheral resistance, and decreased cardiac output. These may be accompanied by violent headache, cerebral haemorrhage, photophobia, retrosternal pain, pallor, fever, intense sweating, pulmonary oedema and vomiting.
Treatment
In case of accidental overdose, as evidenced by excessive blood pressure elevation, discontinue the drug until the condition of the patient stabilises.
Ask anything about Noradrenaline (Norepinephrine) 1 mg/ml concentrate for solution for infusion. The assistant answers only from this leaflet — if the leaflet does not cover it, it will say so. It does not give medical advice.
Answers come from the patient leaflet published on the electronic medicines compendium (emc). They are not medical advice. Ask a pharmacist or your GP if you are unsure. For urgent help call NHS 111, or 999 in an emergency.
We use essential cookies to make the site work. We would also like to set optional cookies to understand how the site is used, so we can improve it. We will not set optional cookies unless you accept. See our cookie policy and privacy policy.