Protamine sulfate Leo Pharma

PATIENT INFORMATION LEAFLET

Leaflet accompanying the packaging: patient information

Protamine sulfate LEO Pharma, 1400 anti-heparin IU/mL

(which corresponds to 10 mg/mL), solution for injection/infusion
Protamine sulfate

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• This product is usually administered by a doctor or nurse. If you have any doubts, consult your doctor, nurse, or pharmacist.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Protamine sulfate LEO Pharma and what is it used for
• 2. Important information 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 is Protamine sulfate LEO Pharma and what is it used for

The active substance is protamine sulfate, which is used as an antidote to counteract the effects of heparin and low molecular weight heparin (LMWH) and reduce the impact of these substances on the body.
Heparins are used to prevent blood clotting and may cause bleeding.
The patient may receive this medicine:

• To help stop bleeding caused by heparin/LMWH
• To prevent frequent bleeding, if the patient has been treated with heparin/LMWH and is to undergo surgery
• To reverse the effects of heparin used in certain types of heart surgery.

2. Important information before using Protamine sulfate LEO Pharma

When not to use Protamine sulfate LEO Pharma

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

Warnings and precautions

Before starting treatment with Protamine sulfate LEO Pharma, discuss it with your doctor, pharmacist, or nurse if the patient:

• is diabetic using insulin (especially protamine insulin)
• is allergic to fish
• is an infertile man (cannot have children) or has undergone a vasectomy (an operation that makes a man infertile)
• has previously been treated with protamine sulfate, protamine insulin, or protamine chloride.

Children and adolescents

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

Protamine sulfate LEO Pharma and other medicines

Tell your doctor or pharmacist about all medicines the patient is taking, has recently taken, or might take.

Pregnancy and breastfeeding

Pregnancy
If the patient is pregnant, thinks she may be pregnant, or plans to have a baby, she should consult her doctor, nurse, or pharmacist before using this medicine.
There is no available information on the use of this product in pregnant women.
Do not use Protamine sulfate LEO Pharma unless absolutely necessary.
Breastfeeding
If the patient is breastfeeding, she should consult her doctor, nurse, or pharmacist before using this medicine.
There is no available information on the use of this medicine in breastfeeding women.
If treatment with protamine sulfate LEO Pharma is necessary, breastfeeding should be discontinued.

Driving and using machines

Protamine sulfate LEO Pharma has no or negligible influence on the ability to drive and use machines.

Protamine sulfate LEO Pharma contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per 5 mL, which means it is essentially 'sodium-free'.

3. How to use Protamine sulfate LEO Pharma

The doctor will decide what dose of Protamine sulfate LEO Pharma is suitable for the patient.
This depends on the results of blood tests to determine how much heparin needs to be counteracted.
Protamine sulfate LEO Pharma is intended for intravenous administration and can be administered by slow injection (over about 10 minutes) into a vein or added to an intravenous infusion solution.
The patient may need additional doses, especially if it is necessary to counteract the effects of LMWH or if the operation is prolonged.
No more than 5 mL of this medicine will be administered in any 10-minute period.

Using more than the recommended dose of Protamine sulfate LEO Pharma

This may interfere with the blood clotting process by prolonging the time it takes for the blood to clot.
If you have any further doubts about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

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

Severe side effects

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

• Severe allergic reaction. Symptoms include severe breathing difficulties, wheezing, swelling of the face and lips, heart problems, and collapse (fainting due to low blood pressure)
• High blood pressure in the lungs. Symptoms include severe breathing difficulties
• Severe and prolonged low blood pressure. Symptoms include slow heart rate, blue skin, feeling of fainting or collapse (especially if Protamine sulfate LEO Pharma is administered too quickly)

Less severe side effects that have been observed during 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 of warmth, skin redness, shortness of breath, and swelling of the deeper layers of the skin (sometimes with swelling of the tongue and airways).

Reporting side effects

If you experience any side effects, including any side effects not listed in this leaflet, tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C, 02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl.
Side effects can also be reported to the marketing authorization holder.
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 the 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 the month stated.
• This medicine does not require any special storage conditions.
• Use immediately after opening the ampoule.
• Any remaining solution should be discarded.
• Only use if the solution is clear and the ampoule is intact.
• After dilution for slow intravenous infusion, the mixture should be used immediately.

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 other information

What Protamine sulfate LEO Pharma contains

• The active substance is protamine sulfate. 1 mL contains 1400 anti-heparin IU of protamine sulfate (10 mg), 5 mL contains 7000 anti-heparin IU of protamine sulfate (50 mg).
• The other ingredients are sodium chloride, hydrochloric acid (for pH adjustment), sodium hydroxide (for pH adjustment), and water for injections.

What Protamine sulfate LEO Pharma looks like and contents of the pack

This product is a solution for injection/infusion, which is a clear, colorless liquid.
Ampoules of 5 mL. Pack of 5 ampoules.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder

LEO Pharma A/S
Industriparken 55
2750 Ballerup
Denmark

Manufacturer

CENEXI
52, rue Marcel et Jacques Gaucher
94120 Fontenay-sous-Bois
France
To obtain more information on this medicine, contact the local representative of the marketing authorization holder:
LEO Pharma Sp. z o.o.
ul. Marynarska 15
02-674 Warsaw
Phone: 22 244 18 40
This medicine is authorized in the Member States of the European Economic Area under the following names:
Protaminsulfat LEO Pharma: Austria, Denmark, Finland, Germany, Iceland, Norway, Sweden, Czech Republic, Slovakia
Protamine sulfaat LEO Pharma: Belgium, Netherlands
Protamine sulfate LEO Pharma: Estonia, Greece, Ireland, Lithuania, Luxembourg, Malta
Sulfato de protamina LEO Pharma: Portugal
Protaminijev sulfat LEO Pharma: Slovenia
Protamina sulfato LEO Pharma: Spain
Protamina solfato LEO Pharma: Italy

Date of last revision of the leaflet:

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Information intended for healthcare professionals only:

Protamine sulfate LEO Pharma

1400 anti-heparin IU/mL (which corresponds to 10 mg/mL) solution for injection/infusion

1 mL contains 1400 anti-heparin IU of protamine sulfate (10 mg)

5 mL contains 7000 anti-heparin IU of protamine sulfate (50 mg)

For more information, see the Summary of Product Characteristics (SPC).

Therapeutic indications:Protamine sulfate may be used to counteract the anticoagulant effect of heparin or LMWH (see SPC).

Dosage and administration

Protamine sulfate is administered by slow intravenous injection over a period of about 10 minutes or as a continuous, slow infusion. The maximum single injection (bolus dose) should not exceed 5 mL (7000 anti-heparin IU/50 mg of protamine sulfate). It is best if the dose is based on coagulation tests. For this purpose, the activated partial thromboplastin time (APTT), activated clotting time (ACT), anti-Xa test, and protamine neutralization test are suitable. Coagulation tests are usually performed 5 to 15 minutes after administration of protamine sulfate. Further doses may be required, as protamine sulfate is eliminated from the blood more quickly than heparin, and especially LMWH. Prolonged absorption after subcutaneous administration of heparin or LMWH may also indicate the need for multiple doses.

Neutralization of heparin

1 mL of Protamine sulfate LEO Pharma (10 mg of protamine sulfate) neutralizes approximately 1400 IU of heparin. Since heparin has a relatively short half-life after intravenous administration (from 30 minutes to 2 hours), the dose of protamine sulfate should be adjusted based on the time elapsed since the discontinuation of intravenous heparin administration. The dose of protamine sulfate in relation to the amount of heparin administered should be reduced if more than 15 minutes have passed since the end of intravenous heparin administration.

Neutralization of low molecular weight heparin (LMWH)

Typically, a dose of 1 mL of Protamine sulfate LEO Pharma (10 mg of protamine sulfate) per 100 anti-Xa IU of LMWH is recommended. Protamine sulfate neutralizes different LMWHs to varying degrees; therefore, for each LMWH, the manufacturer's own guidelines should be consulted in case of overdose. Protamine sulfate only partially neutralizes the anti-Xa activity induced by LMWH, and neutralization will not be more effective if higher doses of protamine sulfate are administered than recommended. The risk of incomplete neutralization with a single injection of protamine sulfate exists when neutralizing subcutaneously administered LMWH. The absorption phase from the injection site then leads to the release of additional LMWH into the circulation (the so-called "depot effect"). In such cases, repeated administration of protamine sulfate or a continuous, slow intravenous infusion may be necessary. When estimating the required dose of protamine sulfate, the half-life of LMWH in relation to the time elapsed since the last dose of LMWH should also be taken into account.

Cardiopulmonary bypass procedures

It is recommended that doses of protamine sulfate be based on coagulation tests. The activated partial thromboplastin time (APTT), activated clotting time (ACT), anti-Xa, and protamine neutralization test at the bedside are suitable for this purpose. Coagulation tests are usually performed 5 to 15 minutes after administration of protamine sulfate. Generally, a dose of 0.1 mL to 0.2 mL (1-2 mg) of Protamine sulfate LEO Pharma is administered intravenously per 100 units of heparin administered.

Special precautions for disposal

Use immediately after opening the ampoule.
Any remaining solution should be discarded.
The medicine can only be used if the solution is clear, without visible particles, and the ampoule is intact. Any unused product or waste material should be disposed of in accordance with local requirements.
Protamine sulfate LEO Pharma can be administered in a slow intravenous infusion, in which case sodium chloride 9 mg/mL should be used. Such mixtures should not be stored.