Label: information for the patient

Protamina sulfate LEO Pharma 1.400 IU anticoagulant (10mg)/ml

injectable solution and for perfusion

protamine, sulfate

Read this label carefully before starting to use this medication, because it contains important information for you.

• Keep this label, as you may need to read it again.
• This product will normally be administered by a doctor or nurse. If you have any questions, consult your doctor, nurse, or pharmacist.
• If you experience adverse effects, consult your doctor, nurse, or pharmacist, even if they are not listed in this label. See section 4.

1. What is Protamina sulfate LEO Pharma and how it is used

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

3. How to use Protamina sulfate LEO Pharma

4. Possible adverse effects

5. Storage of Protamina sulfate LEO Pharma

6. Contents of the package and additional information

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

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

This medication may be used to treat:

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

Do not use Protamina sulfate LEO Pharma:

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

Warnings and precautions

Consult your doctor, pharmacist or nurse before starting to use this medication

• if you are a diabetic using insulin (particularly protamine insulin)
• if you are allergic to fish
• if you are a sterile man (you cannot conceive a child) or if you have undergone a vasectomy (a procedure to sterilize a man)
• if you have been previously treated with protamine sulfate, protamine insulin or chloroprotamine

If you have already received your injection, inform healthcare personnel if you are in any of the above situations. If you are unsure, discuss it with your doctor.

Children and adolescents

This medication is not indicated for use in children and adolescents.

Other medications and Protamina sulfate LEO Pharma

Inform your doctor, nurse or pharmacist if you are taking, have taken recently or may need to take any other medication.

Pregnancy and breastfeeding

Pregnancy

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

No information is available regarding the use of this medication in pregnant women.

Protamina sulfate LEO Pharma should not be used during pregnancy except when clearly necessary.

Breastfeeding

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

No information is available regarding the use of this medication in breastfeeding women.

You should discontinue breastfeeding if treatment with Protamina sulfate LEO Pharma is necessary.

Driving and operating machinery

The influence of this medication on the ability to drive and operate machinery is negligible.

Protamina sulfate LEO Pharma contains sodium

This medication contains less than 1 mmol (23 mg) of sodium per 5 ml; it is essentially “sodium-free”.

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

Protamina sulfate LEO Pharma is for intravenous administration and can be administered as a slow injection (over a period of 10 minutes) into a vein or can be added to the solution contained in your "infusion pump".

You may require additional doses, especially if you need to reverse low molecular weight heparin or if your procedure is long.

You will not be administered more than 5 ml of this medication per 10-minute treatment period.

If you have been administered moreProtamina sulfate LEO Pharma than you should

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

In case of overdose or accidental administration, consult the Toxicological Information Service. Phone 91 562 04 20, or go to the nearest hospital emergency department, accompanied by this leaflet.

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

Like all medications, this medication may produce adverse effects, although not everyone will experience them.

Severe Adverse Effects:

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

• Severe Allergic Reaction. Symptoms include severe respiratory problems, wheezing, facial and lip swelling, heart problems, and collapse (due to low blood pressure)
• Pulmonary Hypertension. Symptoms include severe respiratory problems.
• Severe and Prolonged Decrease in Blood Pressure. Symptoms include low pulse rate, blue skin, feeling of fainting or collapse (especially if Protamina sulfato LEO Pharma is administered very quickly)

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

• Low Blood Pressure. Symptoms include dizziness
• Vomiting
• Back Pain
• Bleeding
• Allergic Reaction, similar to urticaria or other skin eruptions. Symptoms include feeling of heat, skin redness, difficulty breathing, and swelling of the deeper layers of the skin (occasionally with tongue and airway swelling).

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this prospectus. You can also report them through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

• Keep this medication out of the sight and reach of children.
• Do not use this medication after the expiration date that appears on the box and on the label after CAD. The expiration date is the last day of the month indicated.
• This medication does not require special conditions for conservation.

• Use immediately after opening the ampule.
• Dispose of any remaining solution.
• Use only if the solution is transparent and the ampule is intact.
• When diluted for administration as a slow intravenous infusion, the mixture must be used immediately.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of containers and medications that you no longer need. This will help protect the environment.

Composition of Protamina sulfate LEO Pharma

• The active ingredient is protamine sulfate. 1 ml contains 1,400 UI anti-heparin of protamine sulfate (equivalent to 10 mg), 5 ml contain 7,000 UI anti-heparin of protamine sulfate (equivalent to 50 mg).

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

Appearance of Protamina sulfate LEO Pharma and packaging content

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

5 ml ampoules. Packaging sizes of 5 or 50 ampoules.

Only some packaging sizes may be commercially available.

Marketing authorization holder and manufacturer responsible:

Marketing authorization holder

LEO Pharma A/S

55 Industriparken, DK-2750 Ballerup, Denmark.

Manufacturer responsible

CENEXI SAS

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

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

LEO Pharma, S.A.

Via Laietana 33, 7th floor

08003 Barcelona

Spain

Last review date of this leaflet: 09/2014

The detailed information about this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).

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Please cut here and keep this part of the leaflet. Give the rest of the leaflet to the patient.

This information is intended solely for healthcare professionals:

Protamina sulfate LEO Pharma 1,400 UI anti-heparin (10 mg)/ml injectable and perfusion solution

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

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

For more information, see the complete technical datasheet.

Therapeutic indications:This medication may be used to neutralize the anticoagulant effect of heparin or low molecular weight heparin (LMWH) (see technical datasheet).

Dosage and administration

This medication is administered as an intravenous injectionslowlyover a period of about 10 minutes or as an intravenous perfusion slowly. The maximum dose to be administered as a single injection (bolus dose) should not exceed 5 ml (7,000 UI anti-heparin/50 mg). Generally, the dose should be established based on the results of blood coagulation tests. For this purpose, the determination of activated partial thromboplastin time (aPTT), activated coagulation time (ACT), anti-Xa activity and protamine neutralization test are suitable. Blood coagulation tests are usually performed 5–15 minutes after administration of protamine sulfate. Additional doses may be necessary since protamine sulfate is eliminated from the blood more quickly than heparin and especially more quickly than LMWH. Prolonged absorption after subcutaneous administration of heparin or LMWH may also indicate that repeated doses should be administered.

Neutralization of Heparin

1 ml of Protamina sulfate LEO Pharma (10 mg of protamine sulfate) will neutralize approximately 1,400 UI 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 based on the time elapsed since the intravenous administration of heparin was interrupted. The dose of protamine sulfate in relation to the amount of heparin administered should be reduced if more than 15 minutes have elapsed since the end of the intravenous heparin injection.

Neutralization of Low Molecular Weight Heparin (LMWH)

Generally, a dose of 1 ml of Protamina sulfate LEO Pharma (10 mg of protamine sulfate) is recommended for every 1,000 UI anti-Xa of LMWH. Protamine sulfate neutralizes different LMWHs in different ways; therefore, in cases of overdose, the manufacturer's recommendations for the specific LMWH in question should be consulted. Protamine sulfate is only able to partially neutralize the anti-Xa activity of LMWH, and neutralization will not be more effective if doses of protamine sulfate greater than those recommended are administered. There is a risk of incomplete neutralization with a single injection of protamine sulfate in the case of subcutaneous administration of LMWH. The absorption phase from the injection site will result in additional amounts of LMWH reaching the circulation (also known as the 'depot effect'). In these cases, repeated administrations of protamine sulfate or the use of a continuous intravenous perfusion may be necessary. When estimating the dose of protamine sulfate required in relation to the time elapsed since the last dose of LMWH was administered, the half-life of LMWHs should also be taken into account.

Bypass cardiopulmonary procedures

It is recommended to establish the dose of protamine sulfate based on the results of blood coagulation tests. For this purpose, the determination of activated partial thromboplastin time (aPTT), activated coagulation time (ACT), anti-Xa activity and protamine neutralization test are suitable. Blood coagulation tests are usually performed 5–15 minutes after administration of protamine sulfate. Generally, a dose of 0.1 ml to 0.2 ml (1 – 2 mg) of Protamina sulfate LEO Pharma is administered intravenously for every 100 units of heparin administered.

Special precautions for disposal

It should be used immediately after opening the ampoule.

Dispose of any remaining solution.

Only use if the solution is transparent, free of visible particles, and the ampoule is intact. The disposal of unused medication and all materials that have come into contact with it will be carried out in accordance with local regulations.

Protamina sulfate LEO Pharma may be administered as an intravenous perfusion slowly, in which case a solution of sodium chloride 9 mg/ml should be used. Such mixtures should not be stored.