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NORADRENALINE (NOREPINEPHRINE) 1MG/ML CONCENTRATE FOR SOLUTION FOR INFUSION

Active substance(s): NORADRENALINE TARTRATE / NORADRENALINE TARTRATE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Noradrenaline (Norepinephrine) 1 mg/ml Concentrate for Solution for Infusion

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml concentrate for solution for infusion contains 2 mg noradrenaline tartrate
equivalent to 1 mg noradrenaline base.
1 ampoule of 2 ml contains 4 mg noradrenaline tartrate equivalent to 2 mg
noradrenaline base.
1 ampoule of 4 ml contains 8 mg noradrenaline tartrate equivalent to 4 mg
noradrenaline base.
When diluted as recommended, each ml contains 80 micrograms noradrenaline
tartrate equivalent to 40 micrograms noradrenaline base.
Excipient(s) with known effects:
1 ampoule of 2 ml contains 0.29 mmol (or 6.7 mg) sodium.
1 ampoule of 4 ml contains 0.58 mmol (or 13.3 mg) sodium.
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Concentrate for solution for infusion
A clear colourless or yellowish solution
pH: 3.0 – 4.0
Osmolarity: approximately 280 mOsm/l

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Indicated for use as an emergency measure in the restoration of blood pressure in
cases of acute hypotension.

4.2

Posology and method of administration
Posology

Adults
Initial rate of infusion:
When diluted as recommended in section 6.6 (the concentration of the
prepared infusion is 40 mg/litre noradrenaline base (80 mg/litre noradrenaline
tartrate)) the initial rate of infusion, at a body weight of 70 kg, should be
between 10 ml/hour and 20 ml/hour (0.16 to 0.33 ml/min). This is equivalent
to 0.4 mg/hour to 0.8 mg/hour noradrenaline base (0.8 mg/hour to 1.6 mg/hour
noradrenaline tartrate). Some clinicians may wish to start at a lower initial
infusion rate of 5 ml/hour (0.08 ml/min), equivalent to 0.2 mg/hour
noradrenaline base (0.4 mg/hour noradrenaline tartrate).
Titration of dose:
Once an infusion of noradrenaline has been established the dose should be
titrated in steps of 0.05 -0.1 µg/kg/min of noradrenaline base 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).

Patient’s
Weight

50 kg

Noradrenaline Infusion Solution
40 mg/litre (40 µg /ml) noradrenaline base
Posology (µg/kg/min)
Posology
noradrenaline base
(mg/hour)
noradrenaline
base
0.05
0.15
0.1
0.3
0.25
0.75
0.5
1.5

Infusion Rate
(ml/hour)

3.75
7.5
18.75
37.5

60 kg

70 kg

80 kg

90 kg

1
0.05
0.1
0.25
0.5
1
0.05
0.1
0.25
0.5
1
0.05
0.1
0.25
0.5
1
0.05
0.1
0.25
0.5
1

3
0.18
0.36
0.9
1.8
3.6
0.21
0.42
1.05
2.1
4.2
0.24
0.48
1.2
2.4
4.8
0.27
0.54
1.35
2.7
5.4

75
4.5
9
22.5
45
90
5.25
10.5
26.25
52.5
105
6
12
30
60
120
6.75
13.5
33.75
67.5
135

Some clinicians may prefer to dilute to other concentrations. If dilutions other than 40
mg/l are used, check the infusion rate calculation carefully before starting treatment.
Renal or hepatic impairment:
There is no experience in treatment of renally or hepatically impaired patients
Elderly:
As for adults but see section 4.4.
Paediatric population
Not recommended.
Duration of Treatment and Monitoring:
Noradrenaline should be continued for as long as vasoactive drug support is indicated.
The patient should be monitored carefully for the duration of therapy. Blood pressure
should be carefully monitored for the duration of therapy.
Withdrawal of Therapy:
The noradrenaline infusion should be gradually decreased since abrupt withdrawal
can result in acute hypotension.

Route of Administration:
For intravenous use.
Method of administration:
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.
For instructions on dilution of the medicinal product before administration, see
section 6.6.

4.3

Contraindications

Hypersensitivity to noradrenaline tartrate or to any of the excipients listed in section
6.1.
4.4

Special warnings and precautions for use

Noradrenaline should only be administered by healthcare professionals who are
familiar with its use.
Elderly patients may be especially sensitive to the effects of noradrenaline.
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. Similar caution should be observed in patients with
hypotension following myocardial infarction, in patients with Prinzmetal’s variant
angina and in patients with diabetes, hypertension or hyperthyroidism.
Noradrenaline should be used with caution in patients who exhibit profound hypoxia
or hypercarbia.
Noradrenaline should be used only in conjunction with appropriate blood volume
replacement. When infusing noradrenaline, the blood pressure and rate of flow
should be checked frequently to avoid hypertension.
Extravasation of the solution may cause local tissue necrosis. The infusion site should
be checked frequently. If extravasation occurs, the infusion should be stopped and the
area should be infiltrated with phentolamine without delay.
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 the infusion is discontinued, or 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 ischaemic injury.
Contains sodium. To be taken into consideration by patients on a controlled sodium
diet, see section 2.
4.5

Interaction with other medicinal products and other forms of interaction
The use of noradrenaline with volatile halogenated anaesthetic agents, monoamine
oxidase inhibitors, linezolid, tricyclic antidepressants, adrenergic-serotoninergic drugs
or any other cardiac sensitising agents is not recommended because severe, prolonged
hypertension and possible arrhythmias may result.

4.6

Fertility, pregnancy and lactation

Pregnancy
Noradrenaline may impair placental perfusion and induce fetal bradycardia. It may
also exert a contractile effect on the pregnant uterus and lead to fetal asphyxia in late
pregnancy. These possible risks to the fetus should therefore be weighed against the
potential benefit to the mother.
Breastfeeding
No information is available on the use of noradrenaline in lactation.
4.7

Effects on ability to drive and use machines
None stated.

4.8

Undesirable effects
System Organ Class
Undesirable effect
Psychiatric disorders
Anxiety
Nervous system disorders Headache
Cardiac disorders
Arrhythmias (when used in conjunction with cardiac
sensitising agents), bradycardia
Vascular disorders
Hypertension, peripheral ischaemia including gangrene of
the extremities, plasma volume depletion with prolonged
use
Respiratory, thoracic and Dyspnoea

mediastinal disorders
General disorders and
administration site
conditions

Extravasation necrosis at injection site

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 national reporting system listed in Appendix V

4.9

Overdose
Overdosage may result in severe hypertension, reflex bradycardia, marked increase in
peripheral resistance and decreased cardiac output. These may be accompanied by
violent headache, photophobia, retrosternal pain, pallor, intense sweating and
vomiting. In the event of overdosage, treatment should be withdrawn and appropriate
corrective treatment initiated.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Adrenergic and dopaminergic agents, ATC code:
C01CA03
The vascular effects in the doses normally used clinically result from the
simultaneous stimulation of alpha and beta adrenergic receptors in the heart and
vascular system. Except in the heart, its action is predominantly on the alpha
receptors. This results in an increase in the force (and in the absence of vagal
inhibition, in the rate) of myocardial contraction. Peripheral resistance increases and
diastolic and systolic pressures are raised.
The increase in blood pressure may cause a reflex decrease in heart rate.
Vasoconstriction may result in decreased blood flow in kidneys, liver, skin and
smooth muscles. Local vasoconstriction may cause haemostasis and/or necrosis.
The effect on blood pressure disappears 1-2 minutes after stopping the infusion.

5.2

Pharmacokinetic properties

Up to 16% of an intravenous dose is excreted unchanged in the urine with methylated
and deaminated metabolites in free and conjugated forms.

5.3

Preclinical safety data
Most of the adverse effects attributable to sympathomimetics result from excessive
stimulation of the sympathetic nervous system via the different adrenergic receptors.
Noradrenaline may impair placental perfusion and induce fetal bradycardia. It may
also exert a contractile effect on the uterus and lead to fetal asphyxia in late
pregnancy.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Sodium chloride
Sodium hydroxide (for pH adjustment)
Hydrochloric acid (for pH adjustment)
Water for Injections

6.2

Incompatibilities
Noradrenaline must not be mixed with other medicinal products except those
mentioned in section 6.6.
Infusion solutions containing noradrenaline tartrate have been reported to be
incompatible with the following substances: alkalis and oxidising agents, barbiturates,
chlorpheniramine, chlorothiazide, nitrofurantoin, novobiocin, phenytoin, sodium
bicarbonate, sodium iodide, streptomycin.
For compatibility with infusion bags see section 6.6.

6.3

Shelf life
18 months.
After dilution:
Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C
when diluted to 4 mg/litre and 40 mg/litre noradrenaline base in sodium chloride 9
mg/ml (0.9%) solution or glucose 5% solution. However, from a microbiological
point of view, the product should be used immediately. If not used immediately, inuse 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.

6.4

Special precautions for storage

Do not store above 25°C.
For storage conditions after dilution of the medicinal product, see section 6.3.
6.5

Nature and contents of container
Ampoules containing 2 ml and 4 ml of concentrate.
Pack size of 5 ampoules.

6.6

Special precautions for disposal

Dilution instructions:
Dilute before use with glucose 5% solution or sodium chloride 9 mg/ml (0.9%) with
glucose 5 % solution.
Either add 2 ml concentrate to 48 ml glucose 5% solution (or sodium chloride 9
mg/ml (0.9%) with glucose 5% solution) for administration by syringe pump, or add
20 ml of concentrate to 480 ml glucose 5 % solution (or sodium chloride 9 mg/ml
(0.9%) with glucose 5% solution) for administration by drip counter. In both cases
the final concentration of the infusion solution is 40 mg/litre noradrenaline base
(which is equivalent to 80 mg/litre noradrenaline tartrate). Dilutions other than 40
mg/litre noradrenaline base may also be used (see section 4.2). If dilutions other than
40 mg/litre noradrenaline base are used, check the infusion rate calculation carefully
before starting treatment.
The product is compatible with PVC infusion bags.

Any unused medicinal product or waste material should be disposed of in accordance
with local requirements.

7

MARKETING AUTHORISATION HOLDER
Hospira UK Limited
Horizon
Honey Lane
Hurley
Maidenhead
SL6 6RJ
UK

8

MARKETING AUTHORISATION NUMBER(S)
PL 04515/0240

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
05/08/2011

10

DATE OF REVISION OF THE TEXT
11/01/2017

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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