Protamine sulfate Leo Pharma

Package leaflet: Information for the patient

Protamine sulphate LEO Pharma

anti 1400 IU of heparin (10 mg)/ml
Solution for injection or infusion
Protamine sulphate
Please read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• This product will usually be administered by a doctor or nurse. If you have any questions, please consult your doctor or pharmacist.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, nurse or pharmacist. See section 4.

Contents of this leaflet

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

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

The active substance is protamine sulfate, which is used as an anti-heparin agent, i.e. to block the action of heparin and low molecular weight heparins, and to reduce the effect of these substances on the body.
Heparins are used to prevent blood clotting and may cause bleeding.
You may be given this medicine:

• to help stop bleeding caused by heparin or low molecular weight heparin;
• to prevent bleeding if you have been treated with heparin or low molecular weight heparin and are about to undergo surgery;
• to reverse the effect of heparin used during certain types of cardiac surgery.

2. What you need to know before using Protamine sulphate LEO Pharma

Do not take Protamine sulphate LEO Pharma:
if you are allergic to protamine sulphate 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 you are given Protamine sulphate LEO Pharma if:

• you are a diabetic using insulin (particularly protamine insulin)
• you are allergic to fish
• you are an infertile man (unable to have children) or have had a vasectomy (a procedure causing sterility in men)
• you have previously been treated with protamine sulphate, protamine insulin, or protamine chloride.

If you have previously received an injection, inform the hospital staff if you have any of the conditions listed above. If you are unsure, speak with your doctor.

Children and adolescents
Protamine sulphate LEO Pharma is not indicated for use in children and adolescents.

Other medicines and Protamine sulphate LEO Pharma
Tell your doctor, nurse, or pharmacist if you are taking, have recently taken, or might take any other medicines.

Pregnancy and breastfeeding
Pregnancy
If you are pregnant, suspect you may be pregnant, or are planning a pregnancy, consult your doctor, nurse, or pharmacist before taking this medicine.
There is no available information on the use of this product in pregnant women.
Protamine sulphate LEO Pharma should not be used unless strictly necessary.

Breastfeeding
If you are breastfeeding, consult your doctor, nurse, or pharmacist before taking this medicine.
There is no available information on the use of this product in breastfeeding women.
If treatment with Protamine sulphate LEO Pharma is necessary, breastfeeding must be discontinued.

Driving and using machines
Protamine sulphate LEO Pharma has no effect or has a negligible effect on the ability to drive vehicles and operate machinery.

Protamine sulphate 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 Protamine sulphate LEO Pharma

Your doctor will decide the correct amount of Protamine sulphate LEO Pharma for you. The dose depends on the results of blood tests performed to determine how much heparin needs to be neutralized.
Protamine sulphate LEO Pharma is administered intravenously by slow injection into a vein (over approximately 10 minutes) or may be added to your intravenous infusion.
Additional doses may be required, especially if reversing the effect of low molecular weight heparin or if the surgical procedure takes a long time.
You will not be given more than 5 ml of this medicine within 10 minutes.
If you have been given more Protamine sulphate LEO Pharma than you should have received
This may interfere with the blood clotting process, increasing the time required for blood to clot.
If you have any further questions about the use of this product, consult your doctor, nurse, or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.

Serious side effects:

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

• Severe allergic reaction. Symptoms include severe breathing problems, shortness of breath, swelling of the face and lips, heart problems, collapse (fainting due to low blood pressure).
• High blood pressure in the lungs (pulmonary hypertension). Symptoms include severe breathing difficulties.
• Severe and prolonged low blood pressure. Symptoms include slow heart rate, blue skin, feeling faint or collapse (particularly if Protamine sulfate LEO Pharma has been administered too rapidly).

The following less serious side effects have been observed with the administration of Protamine sulfate 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, shortness of breath, and swelling of the deeper layers of the skin (occasionally with swelling of the tongue and airways).

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effect not listed in this leaflet. You can also report side effects directly via the national reporting system at:
https://www.aifa.gov.it/content/segnalazioni-reazioniavverse
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Protamine sulfate LEO Pharma

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the carton and label after EXP. The expiry date refers to the last day of that month.
• This medicine does not require any special storage conditions.
• Use immediately after opening the vial.
• Any unused portion of the solution must be discarded.
• This medicine should only be used if the solution is clear and the vial is intact.
• When diluted for administration as a slow intravenous infusion, the mixture must be used immediately.

Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of
medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What Protamina solfato LEO Pharma Contains

• The active substance is protamine sulfate. 1 ml contains 10 mg of protamine sulfate neutralizing 1400 IU of heparin; 5 ml contain 50 mg of protamine sulfate neutralizing 7000 IU of heparin.
• The other components are: sodium chloride, hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), and water for injections.

Description of the Appearance of Protamina solfato LEO Pharma and Contents of the Pack
This product is a clear, colourless liquid supplied as a solution for injection or infusion. 5 ml vials. Packs of 5 or 50 vials.
Not all 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

Detailed information on this medicinal product is available on the website of:
{Member State Agency}
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The following information is intended for healthcare professionals only
Protamine sulfate LEO Pharma neutralizing 1400 IU of heparin (10 mg)/ml
solution for injection or infusion
1 ml contains 10 mg of protamine sulfate neutralizing 1400 IU of heparin
5 ml contain 50 mg of protamine sulfate neutralizing 7000 IU of heparin
See the Summary of Product Characteristics (SmPC) for further details.
Therapeutic indications: Protamine sulfate may be used to counteract the anticoagulant effects of heparin or low molecular weight heparin (LMWH) (see SmPC).

Dosage and Method of Administration
Protamine sulfate is administered as a slow intravenous injection over approximately 10 minutes or as a slow, continuous intravenous infusion. The maximum single injection (bolus dose) must not exceed 5 ml (i.e., 50 mg of protamine sulfate, neutralizing 7000 IU of heparin). Preferably, dosing should be based on repeated coagulation tests: activated partial thromboplastin time (APTT), activated coagulation time (ACT), anti-Xa assay, and protamine neutralization test at the patient's bedside are suitable for this purpose. Coagulation tests are usually performed 5 to 15 minutes after administration of protamine sulfate. Additional doses may be required, as protamine sulfate is eliminated from the blood more rapidly than heparin and especially than LMWH. Prolonged absorption after subcutaneous administration of heparin or LMWH may also indicate the need for repeated dosing.

Neutralization of Heparin
1 ml of Protamine sulfate LEO Pharma (equivalent to 10 mg of protamine sulfate) neutralizes approximately 1400 IU of heparin. Since heparin has a relatively short half-life when administered intravenously (30 minutes – 2 hours), the dose of protamine sulfate should be adjusted according to the time elapsed since discontinuation of intravenous heparin administration. The dose of protamine sulfate relative to the amount of heparin administered should be reduced if more than 15 minutes have passed since stopping the intravenous heparin infusion.

Neutralization of Low Molecular Weight Heparin (LMWH)
A dose of 1 ml of Protamine sulfate LEO Pharma (equivalent to 10 mg of protamine sulfate) per 1000 IU anti-Xa of LMWH is generally recommended. Protamine sulfate neutralizes different LMWHs to varying degrees; therefore, in cases of overdose, refer to the guidelines provided by the manufacturer of the administered LMWH (see section 5.1). Protamine sulfate only partially neutralizes the anti-Xa activity of LMWH, and administering doses of protamine sulfate higher than those recommended will not achieve greater neutralization.

The risk of incomplete neutralization with a single dose of protamine sulfate exists when neutralizing subcutaneously administered LMWH. The absorption phase from the injection site leads to additional release of LMWH into the circulation (the so-called "depot effect"). In such cases, repeated administrations of protamine sulfate may be necessary, or a slow, continuous intravenous infusion may be used. The half-life of LMWH should also be considered when estimating the required dose of protamine sulfate relative to the time elapsed since the last LMWH dose.

Cardiopulmonary Bypass Procedures
Doses of protamine sulfate should be determined based on coagulation tests: activated partial thromboplastin time (APTT), activated coagulation time (ACT), anti-Xa assay, and protamine neutralization test at the patient's bedside are suitable for this purpose. Coagulation tests are generally performed 5 to 15 minutes after administration of protamine sulfate. Typically, an intravenous dose of 0.1 ml to 0.2 ml (1–2 mg) of Protamine sulfate LEO Pharma per 100 units of administered heparin is recommended.

Special Precautions for Disposal
Use immediately after opening the vial.
Any unused portion of the solution must be discarded.
The medicine should only be used if the solution is clear, free from visible particles, and the vial is intact.
Unused medicine and waste material derived from this medicine must be disposed of in accordance with local regulations.
Protamine sulfate LEO Pharma may be administered as a slow intravenous infusion, in which case a 9 mg/ml sodium chloride solution should be used.
Such mixtures must not be stored.