Protamine sulfate Leo Pharma 1.400 IU anti-heparin (10 mg)/ml solution for injection and infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Protamine sulfate LEO Pharma 1,400 heparin-neutralizing units (10 mg)/ml

solution for injection and infusion

protamine, sulfate

Read the entire 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.
• This product is normally administered by a doctor or nurse. If you have any questions, consult your doctor, nurse, or pharmacist.
• If you experience any adverse effects, consult your doctor, nurse, or pharmacist, even if they are effects not listed in this leaflet. See section 4.

Leaflet contents

1. What Protamine sulfate LEO Pharma is and what it is used for
2. What you need to know before using Protamine sulfate LEO Pharma
3. How to use Protamine sulfate LEO Pharma
4. Possible side effects
5. How to store Protamine sulfate LEO Pharma
6. Contents of the pack and other information

1. What Protamina sulfato LEO Pharma is and what it is used for

The active substance is protamine sulfate, which is used as an anti-heparin agent to block the action of heparin and low molecular weight heparins, and to reduce the effects of these substances in the body.

Heparins are used to prevent blood clotting and therefore may cause bleeding.

You may be treated with this medicine:

• To help stop bleeding caused by administration of heparin/low molecular weight heparin
• To prevent excessive bleeding if you have been treated with heparin/low molecular weight heparin and are about to undergo a procedure
• To reverse the effect of heparin used during certain types of heart surgery

2. What you need to know before starting to use Protamine sulfate LEO Pharma

Do not use Protamine sulfate LEO Pharma:

if you are allergic to protamine sulfate or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before using this medicine

• if you are a diabetic using insulin (particularly protamine insulin)
• if you are allergic to fish
• if you are a sterile man (unable to father a child) or have had a vasectomy (a procedure to sterilize a man)
• if you have previously been treated with protamine sulfate, protamine insulin, or protamine chloride

If you have already received your injection, inform the healthcare staff if any of the above situations apply to you. If you are unsure, discuss this with your doctor.

Children and adolescents

This medicine is not intended for use in children and adolescents.

Other medicines and Protamine sulfate LEO Pharma

Tell your doctor, nurse, or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Pregnancy and breastfeeding

Pregnancy

If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor, nurse, or pharmacist before using this medicine.

There is no available information regarding the use of this medicine in pregnant women.

Protamine sulfate LEO Pharma should not be used during pregnancy unless clearly necessary.

Breastfeeding

If you are breastfeeding, consult your doctor, nurse, or pharmacist before using this medicine.

There is no available information regarding the use of this medicine in breastfeeding women.

Breastfeeding must be discontinued if treatment with Protamine sulfate LEO Pharma is required.

Driving and using machines

The effect of this medicine on the ability to drive and operate machinery is negligible or none.

Protamine sulfate LEO Pharma contains sodium

This medicine contains less than 1 mmol (23 mg) of sodium per 5 ml; i.e., essentially “sodium-free”.

3. How to use Protamina sulfato LEO Pharma

Your doctor will determine the appropriate amount of Protamina sulfato LEO Pharma for you. This depends on the results of blood tests performed to determine how much heparin needs to be neutralized.

Protamina sulfato LEO Pharma is for intravenous use and may be administered either as a slow injection (over approximately 10 minutes) into a vein or added to the solution in your intravenous infusion bag.

You may require additional doses, especially if reversal of low molecular weight heparin is needed or if your procedure is prolonged.

You will not be administered more than 5 ml of this medicine during each 10-minute treatment period.

If you have been given more Protamina sulfato LEO Pharma than you should have

This may interfere with blood clotting processes, increasing the time required for blood to clot.

In case of overdose or accidental administration, contact the Toxicology Information Service at telephone number 91 562 04 20, or go immediately to the nearest hospital emergency department, taking this leaflet with you.

If you have any further questions about the use of this product, ask your doctor, nurse, or pharmacist.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Serious adverse effects:

If you experience any of the following adverse effects, you must contact your doctor, nurse, or local hospital immediately for emergency assistance:

• Severe allergic reaction. Symptoms include severe breathing problems, wheezing, swelling of the face and lips, heart problems, collapse (fainting due to low blood pressure)
• High blood pressure in the lungs. Symptoms include severe breathing difficulties.
• Severe and prolonged decrease in blood pressure. Symptoms include a low pulse rate, bluish skin, feeling faint or collapse (especially if Protamina sulfato LEO Pharma is administered too rapidly)

The following less serious adverse effects have been observed with administration of Protamina sulfato LEO Pharma:

• Low blood pressure. Symptoms include dizziness
• Vomiting
• Back pain
• Bleeding
• Allergic reaction, similar to hives or other skin rashes. Symptoms include feeling hot, skin redness, difficulty breathing, and swelling of the deeper layers of the skin (occasionally with swelling of the tongue and airways).

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Conservation of Protamine sulphate LEO Pharma

• 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 and label after EXP. The expiry date refers to the last day of the month indicated.

• This medicine does not require any special storage conditions.

• Use immediately after opening the ampoule.

• Discard any unused solution.

• Use only if the solution is clear and the ampoule is undamaged.

• When diluted for administration as a slow intravenous infusion, the mixture must be used immediately.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Protamine sulphate LEO Pharma

• The active substance is protamine sulphate. 1 ml contains 1,400 anti-heparin units (IU) of protamine sulphate (equivalent to 10 mg); 5 ml contain 7,000 anti-heparin IU of protamine sulphate (equivalent to 50 mg).

• The other components are: sodium chloride, hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), and water for injections.

Appearance of Protamine sulphate LEO Pharma and contents of the pack

This product is presented as an injectable and perfusion solution, a colourless and transparent liquid.

Ampoules of 5 ml. Pack sizes of 5 or 50 ampoules.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer:

Marketing Authorisation Holder

LEO Pharma A/S
55 Industriparken, DK-2750 Ballerup, Denmark.

Manufacturer

CENEXI SAS
52, rue Marcel et Jacques Gaucher, 94120 Fontenay-sous-Bois, France.

Further information on this medicinal product is available from the local representative of the Marketing Authorisation Holder:

Laboratorios LEO Pharma, S.A.
Via Laietana 33, 7th floor
08003 Barcelona
Spain

Date of the most recent review of this leaflet: 09/2014

Detailed information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/).

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Please cut along this line and retain this section of the leaflet. Hand over the remainder of the leaflet to the patient.

This information is intended for healthcare professionals only:

Protamine sulphate LEO Pharma 1,400 anti-heparin IU (10 mg)/ml solution for injection and for infusion

1 ml contains 1,400 anti-heparin IU of protamine sulphate (equivalent to 10 mg)

5 ml contain 7,000 anti-heparin IU of protamine sulphate (equivalent to 50 mg)

For more information, see the full summary of product characteristics.

Therapeutic indications: This medicinal product may be used to neutralise the anticoagulant effect of heparin or LMWH (see summary of product characteristics).

Dosage and method of administration

This medicinal product is administered as a slow intravenous injection over approximately 10 minutes or as a slow intravenous infusion. The maximum dose to be administered as a single injection (bolus dose) must not exceed 5 ml (7,000 anti-heparin IU / 50 mg). Generally, the dose should be determined based on coagulation test results. For this purpose, activated partial thromboplastin time (aPTT), activated coagulation time (ACT), anti-Xa activity, and protamine neutralisation test are suitable. Coagulation tests are usually performed 5–15 minutes after administration of protamine sulphate. Additional doses may be required, as protamine sulphate is eliminated from the blood more rapidly than heparin, and especially more rapidly than LMWH. Prolonged absorption after subcutaneous administration of heparin or LMWH may also indicate the need for repeated dosing.

Neutralisation of Heparin

1 ml of Protamine sulphate LEO Pharma (10 mg of protamine sulphate) will neutralise approximately 1,400 IU of heparin. Since heparin has a relatively short half-life when administered intravenously (30 minutes – 2 hours), the dose of protamine sulphate should be adjusted according to the time elapsed since the discontinuation of intravenous heparin administration. The dose of protamine sulphate relative to the amount of heparin administered should be reduced if more than 15 minutes have passed since the end of the intravenous heparin injection.

Neutralisation of Low Molecular Weight Heparin (LMWH)

Generally, a dose of 1 ml of Protamine sulphate LEO Pharma (10 mg of protamine sulphate) per 1,000 anti-Xa IU of LMWH is recommended. Protamine sulphate neutralises different LMWHs to varying degrees; therefore, in cases of overdose, the manufacturer's recommendations for the specific LMWH should be consulted. Protamine sulphate only partially neutralises the anti-Xa activity of LMWH, and administering higher than recommended doses of protamine sulphate will not enhance neutralisation. There is a risk of incomplete neutralisation with a single dose of protamine sulphate when neutralising subcutaneously administered LMWH. The absorption phase from the injection site may result in additional amounts of LMWH entering the circulation (also known as the 'depot effect'). In such cases, repeated administrations of protamine sulphate or a continuous slow intravenous infusion may be necessary. When estimating the required dose of protamine sulphate in relation to the time elapsed since the last LMWH dose, the half-life of LMWHs should also be taken into account.

Cardiopulmonary bypass procedures

The dose of protamine sulphate should be based on coagulation test results. For this purpose, activated partial thromboplastin time (aPTT), activated coagulation time (ACT), anti-Xa activity, and protamine neutralisation test are suitable. Coagulation tests are usually performed 5–15 minutes after administration of protamine sulphate. Generally, a dose of 0.1 ml to 0.2 ml (1–2 mg) of Protamine sulphate LEO Pharma intravenously per 100 units of heparin administered is recommended.

Special precautions for disposal

Use immediately after opening the ampoule.

Discard any unused solution.

Only use if the solution is clear, free from visible particles, and the ampoule is intact. Disposal of unused medicine and all materials that have come into contact with it must be carried out in accordance with local regulations.

Protamine sulphate LEO Pharma may be administered as a slow intravenous infusion, in which case a sodium chloride 9 mg/ml solution should be used. Such mixtures must not be stored.