Noradrenaline (Norepinephrine) 1:1000 or Levophed

N

1. Name Of The Medicinal Product

Noradrenaline (Norepinephrine) 1:1000 or Levophed

concentrate for solution for infusion

2. Qualitative And Quantitative Composition

Noradrenaline Tartrate 2 mg/ml

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Concentrate for solution for infusion

4. Clinical Particulars 4.1 Therapeutic Indications

Norepinephrine 1:1000 is recommended for use as an emergency measure in the restoration of blood pressure in cases of acute hypotension.

4.2 Posology And Method Of Administration

Route of Administration:

For intravenous use.

Route and method of infusion:

Norepinephrine 1:1000 should be administered in 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.

Dilution instructions:

Norepinephrine 1:1000 should be diluted either with dextrose 5%, or with isotonic dextrose saline.

Adults:

Either add 2 ml of Norepinephrine 1:1000 to 48 ml 5% dextrose for administration by syringe pump, or add 20 ml of Norepinephrine 1:1000 to 480 ml 5% dextrose for administration by drip counter.

In both cases the final concentration of the infusion solution is 80 mg/litre norepinephrine tartrate, which is equivalent to 40 mg/litre norepinephrine base. 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 0.33 ml/min). This is equivalent to 0.8 mg/hr to 1.6 mg/hr norepinephrine tartrate (or 0.4 mg/hr to 0.8 mg/hr norepinephrine base).

Titration of dose:

Once an infusion of norepinephrine 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 80 mm Hg).

Duration of Treatment and Monitoring:

Norepinephrine should be continued for as long as vasoactive drug support is indicated. The patient should be monitored carefully for the duration of norepinephrine therapy.

Elderly.

As for adults but see Precautions.

Children:

Not recommended.

4.3 Contraindications

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, norepinephrine should be used with caution in patients receiving these or any other cardiac sensitising agent or who exhibit profound hypoxia or hypercarbia.

Particular caution should be observed in patients with coronary, mesenteric or peripheral vascular thrombosis because norepinephrine may increase the ischemia and extend the area of infarction. Similar caution should be observed in patients with hypotension following myocardial infarction and in patients with Prinzmetal's variant angina.

4.4 Special Warnings And Precautions For Use

Norepinephrine should be used only in conjunction with appropriate blood volume replacement. When infusing norepinephrine, 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 area should be infiltrated with phentolamine without delay.

It has been suggested that phentolamine may be added directly to the infusion flask to act as an antidote against sloughing without affecting the vasopressor activity of norepinephrine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Norepinephrine should be used with extreme caution in patients receiving monoamine oxidase inhibitors or tricyclic antidepressants because severe, prolonged hypertension may result. The elderly may be especially sensitive to the effects of norepinephrine.

4.6 Pregnancy And Lactation

Norepinephrine 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.

4.7 Effects On Ability To Drive And Use Machines

None stated.

4.8 Undesirable Effects

Hypertension may occur, which may be associated with bradycardia as well as headache and peripheral ischemia, including gangrene of the extremities. Cardiac arrhythmias may arise when norepinephrine is used in conjunction with cardiac sensitising agents, and may be more likely in patients with hypoxia or hypercarbia. Prolonged administration may result in plasma volume depletion.

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 of norepinephrine in the doses usually 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.

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

None stated.

6. Pharmaceutical Particulars 6.1 List Of Excipients

Sodium Chloride

Water for Injections.

This medicinal product contains sodium

? 2 ml container contains 0.29 mmol (or 6.7 mg) sodium per container.

? 4 ml container contains 0.58 mmol (or 13.3 mg) sodium per container.

? 20 ml container contains 2.9 mmol (or 67 mg) sodium per container.

To be taken into consideration by patients on a controlled sodium diet.

6.2 Incompatibilities

Infusion solutions containing norepinephrine 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.

6.3 Shelf Life

18 months.

6.4 Special Precautions For Storage

Do not store above 25°C. Keep the container in the outer carton.

6.5 Nature And Contents Of Container

2ml, 4ml and 20ml ampoules packed in boxes of 5.

6.6 Special Precautions For Disposal And Other Handling

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

7. Marketing Authorisation Holder

Hospira Enterprises BV.

Randstad 22-11, 1316 BN Almere,

The Netherlands

8. Marketing Authorisation Number(S)

PL 23061/0006

9. Date Of First Authorisation/Renewal Of The Authorisation

1 July 2005

10. Date Of Revision Of The Text

October 2010

Noradrenaline Norepinephrine 1 1000 or Levophed

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