NORAGES 1 mg/ml INJECTABLE SOLUTION

Introduction

PACKAGE LEAFLET: INFORMATION FOR THE USER

NORAGES 1 mg/ml solution for injection

L-norepinephrine base

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

Contents of the pack and other information:

1. What is Norages and what is it used for
2. What you need to know before you use Norages
3. How to use Norages
4. Possible side effects
5. 5. Storage of Norages
6. Contents of the pack and further information

1. What is Norages and what is it used for

Norages is a medicine that belongs to the group of "adrenergic and dopaminergic agents", which acts by increasing blood pressure.

Norages is indicated for the treatment of acute hypotension (decrease in blood pressure).

2. What you need to know before you use Norages

Do not use Norages:

• if you are allergic (hypersensitive) to L-norepinephrine bitartrate monohydrate or any of the other ingredients of this medicine.
• if you are going to be administered other medicines such as halothane or cyclopropane during anesthesia.
• if you have ulcers or gastrointestinal bleeding.

Be careful with Norages if:

• You are diabetic.
• You have hyperthyroidism.
• Your oxygenation status is insufficient.
• You have any occlusive disease (obstructive) such as arteriosclerosis (hardening of the arteries), Buerger's disease (inflammation of a vein with thrombus formation), diabetes mellitus.
• You have had a thrombosis.

Warnings and precautions

Consult your doctor or pharmacist before starting to use this medicine.

Using Norages with other medicines

Tell your doctor or pharmacist that you are using, have recently used, or may need to use any other medicine.

Certain medicines may interact with Norages, and it may be necessary to change the dose of Norages and/or these medicines and administer them with caution.

It is important that you inform your doctor if you are using or have recently used any of the following medicines:

• Organic anesthetics.
• Tricyclic antidepressants (used to treat depression) or maprotiline.
• Digitalis glycosides (heart medicines).
• Ergoloid mesylates or ergotamine (migraine medicines).
• Levodopa (medicine for Parkinson's disease treatment).
• Cocaine.
• Guanadrel and guanethidine (medicines for hypertension treatment).
• Chlorpheniramine hydrochloride, tripelennamine hydrochloride (allergy medicines) and desipramine (medicine for depression treatment).
• Antihistamines (allergy medicines).
• Amphetamines (central nervous system stimulant medicine).
• Dihydroergotamine (migraine medicine), ergometrine, methylergometrine (medicines for postpartum or abortion hemorrhage treatment) or methysergide (migraine medicine).
• Doxapram (respiratory stimulant medicine).
• Mazindol (obesity treatment medicine).
• Meacamylamine (smoking cessation medicine) or methyldopa (arterial hypertension medicine).
• Methylphenidate (central nervous system stimulant medicine).
• Rauvolfia alkaloids (arterial hypertension medicine).
• Other sympathomimetics (medicines that increase blood pressure).
• Thyroid hormones (metabolism disorder treatment).
• Monoamine oxidase inhibitors (MAOIs) (depression treatment medicines).
• Medicines for tension or to increase urine elimination (diuretics).
• Beta-adrenergic blockers (medicines to reduce blood pressure).
• Desmopressin (medicine used for uncontrolled nighttime urination), lysine vasopressin or vasopressin (medicines for hypotension and antidiuretic treatment).
• Lithium (medicine for mental illness treatment).

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine, as there may be risks for the unborn child.

It is not known whether Norages is excreted in breast milk, so your doctor will assess the need for its administration.

Norages 1 mg/ml contains sodium.

This medicine contains less than 23 mg (1 mmol) of sodium per 4 ml ampoule, so it is considered essentially "sodium-free".

3. How to use Norages

Follow exactly the administration instructions of Norages 1 mg/ml indicated by your doctor. In case of doubt, consult your doctor again.

Norages 1 mg/ml is administered intravenously by a healthcare professional.

Adults

The initial dose is administered at a rate of 8 to 12 micrograms (0.008 to 0.012 mg) (base) per minute. For maintenance, the rate is adjusted to 2 to 4 micrograms (0.002 to 0.004 mg) (base) per minute.

In the case of septic shock, the doses should be adjusted to around 0.5 micrograms/kg/min (up to a maximum of 1.0 micrograms/kg/min).

Children

Intravenous infusion, 0.1 micrograms (base) per kg per minute. Up to a maximum of 1 microgram (base) per kg per minute.

If you use more Norages than you should:

A severe increase in blood pressure may occur with intense headache, photophobia, acute retrosternal pain, pharyngeal pain, pallor, and intense sweating, and vomiting.

In case of overdose or accidental ingestion, consult the Toxicology Information Service. Phone: 91 - 5620420.

4. Possible side effects

Like all medicines, Norages can cause side effects, although not everybody gets them.

If the liquid leaks out of the vein, it can cause destruction of the surrounding tissue.

A reduction in heart rate may occur.

Prolonged use can decrease cardiac output.

Prolonged administration of this type of substance can cause loss of blood fluids, which, if not corrected, can cause a relapse in blood pressure when treatment is stopped.

A severe narrowing of the body's and visceral veins (e.g., decreased renal blood flow) with decreased blood flow and tissue perfusion, resulting in tissue hypoxia, increased blood acidity, and damage due to lack of blood flow, may occur.

Although rare, the following symptoms may occur during its application, requiring medical attention:

Skin disorders: Pallor of the skin along the infusion vein, scarification, bluish discoloration, flushing or redness of the skin, skin rash, urticaria, or pruritus.

Cardiovascular system disorders: Irregular heartbeats, decreased heart rate.

Respiratory system disorders: Wheezing or difficulty breathing.

General disorders: Severe dizziness or feeling of fainting.

Less frequently, the following symptoms may occur, requiring medical attention only if they persist or are bothersome:

Skin disorders: Pallor.

Cardiovascular system disorders: Heart palpitations.

Nervous system disorders: Anxiety or restlessness, sleep problems, tremors, headache.

General disorders: Dizziness, swelling in the neck.

In sensitive individuals, such as those with nervous system disorders or hyperthyroidism, it can cause:

Nervous system disorders: Fear, anxiety, pulsating headache, and breathing difficulties.

Cardiovascular system disorders: Pallor, tachycardia, palpitations, slight increase in blood pressure.

If you experience side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report them directly through the Spanish Medicines and Healthcare Products Agency (AEMPS) website: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Norages

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of the month stated.

Do not store above 25°C. Store in the original package to protect from light.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and further information

Composition of Norages

The active substance is norepinephrine (L-norepinephrine) base.

Each ml of solution contains 1 mg of norepinephrine (L-norepinephrine) base equivalent to 2 mg of norepinephrine (L-norepinephrine) bitartrate monohydrate.

Each 4 ml ampoule contains 4 mg of norepinephrine (L-norepinephrine) base equivalent to 8 mg of norepinephrine (L-norepinephrine) bitartrate monohydrate.

The other ingredients (excipients) are sodium chloride and water for injections.

Appearance and packaging

Norages 1 mg/ml is an injectable solution presented in packs containing 10 ampoules of 4 ml.

Marketing authorization holder and manufacturer

Altan Pharmaceuticals, S.A.

C/ Cólquide 6, Portal 2, 1st floor, office F

Edificio Prisma

28230 Las Rozas - Madrid, Spain

Manufacturer:

Laboratoire RENAUDIN

Z.A. Errobi

64250 Itxassou, France

This leaflet was approved in July 2019

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Healthcare Products (AEMPS) http://www.aemps.gob.es

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This information is intended only for healthcare professionals:

Dosage and administration

Norepinephrine should be administered intravenously:

Usual dose for adults

The initial dose is administered at a rate of 8 to 12 micrograms (0.008 to 0.012 mg) (base) per minute, adjusting the administration rate to establish and maintain the desired blood pressure.

For maintenance, the rate is adjusted to 2 to 4 micrograms (0.002 to 0.004 mg) (base) per minute, titrating the dosage according to the patient's response.

In the case of septic shock, the doses should be adjusted to around 0.5 micrograms/kg/min (up to a maximum of 1.0 micrograms/kg/min) to achieve the desired mean blood pressure. It is recommended to administer it together with doses of 2-2.5 micrograms/kg/min of dopamine, which counteract vasoconstriction, ensuring good renal and splenic circulation.

• To prepare the solution for intravenous infusion of norepinephrine, add 4 mg of L-norepinephrine (base) to 1 liter of 5% glucose solution. The resulting solution will contain 4 micrograms (0.004 mg) of L-norepinephrine (base) per ml. Note that 1 mg of L-norepinephrine bitartrate is equivalent to 0.5 mg of L-norepinephrine base.

Duration of treatment

The infusion should be continued until adequate blood pressure and tissue perfusion are maintained without treatment. The norepinephrine infusion should be gradually reduced, avoiding abrupt interruption. In some cases of vascular collapse due to acute myocardial infarction, treatment was required for up to six days.

Usual pediatric dose

Intravenous infusion, 0.1 micrograms (base) per kg per minute, gradually adjusting the administration rate to achieve the desired blood pressure, up to 1 microgram (base) per kg per minute.

• When added to local anesthetics, these solutions contain a concentration of norepinephrine around 1:200,000 (5 micrograms/ml).

It should be avoided:

• Norepinephrine should not be used as the sole therapy in hypotensive patients due to hypovolemia, except as an emergency measure to maintain coronary and cerebral arterial perfusion until volume replacement therapy is completed.
• Its administration should be avoided in the veins of the lower limbs of elderly patients and those with occlusive diseases due to possible vasoconstriction.
• Accidental cases may occur where, if adequate precautions are not taken, extravasation or even gangrene may occur. To avoid tissue necrosis and scarification in the areas where extravasation has occurred, the area should be immediately infiltrated with 10 to 15 ml of sodium chloride solution containing 5 to 10 mg of phentolamine. A syringe with a fine hypodermic needle should be used, and the solution should be infiltrated abundantly throughout the area. If the area is infiltrated within 12 hours, the sympathetic blockade with phentolamine produces immediate and noticeable local hyperemic changes.
• The lost blood volume should be replaced as completely as possible before administering any vasopressor.

Special precautions for use

• Before administration, norepinephrine injectable should be diluted with 5% glucose in water or 5% glucose in sodium chloride solution. Sodium chloride solution alone should not be used.
• To prepare the solution for intravenous infusion of norepinephrine, add 4 mg of L-norepinephrine (base) to 1 liter of 5% glucose solution. The resulting solution will contain 4 micrograms (0.004 mg) of L-norepinephrine (base) per ml. Note that 1 mg of L-norepinephrine bitartrate is equivalent to 0.5 mg of L-norepinephrine base.
• A controlled drip system should be used to achieve an accurate estimate of the flow rate in drops per minute. The infusion should be administered in the veins of the upper limbs.
• The catheter ligature technique should be avoided, if possible, because the obstruction of blood flow around the tube can cause stasis and an increase in the local concentration of norepinephrine.
• The injectable should not be used if it has a brown color or contains precipitate.

Overdose

Symptoms

Overdose causes severe hypertension with intense headache, photophobia, acute retrosternal pain, pharyngeal pain, pallor, and intense sweating, and vomiting.

Treatment of emergency, antidotes

The recommended treatment for norepinephrine overdose includes:

• suspending the medication
• adequate fluid and electrolyte replacement therapy

for hypertensive effects: if necessary, an alpha-adrenergic blocker can be administered intravenously with 5 to 10 mg of phentolamine.