CEPROTIN 500 IU POWDER AND SOLVENT FOR INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the User

CEPROTIN500UI powder and solvent for solution for injection.

Human Protein C

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. See section 4.

Contents of the pack

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

1. What is CEPROTIN and what is it used for

CEPROTIN belongs to a class of medicines called antithrombotics. This medicine contains Protein C, a natural protein synthesized in the liver and present in your blood. Protein C has an important role in preventing excessive clot formation and is therefore used to prevent and/or treat intravascular thrombosis.

CEPROTIN is used in the treatment and prevention of thrombotic and hemorrhagic lesions (called purpura fulminans) in patients with severe congenital Protein C deficiency. Additionally, CEPROTIN may be used to treat a rare complication of a medicine that prevents blood clot formation (anticoagulant medication called coumarin) that can lead to severe skin lesions (necrosis).

Furthermore, CEPROTIN is used to prevent thrombosis in patients with severe congenital Protein C deficiency if one or more of the following situations occur:

• if surgery or invasive therapy is imminent
• while coumarin therapy (anticoagulant medication) is being initiated
• when coumarin therapy is not sufficient
• when coumarin therapy is not possible

2. What you need to know before you use CEPROTIN

Do not use CEPROTIN

• if you are allergic to human Protein C or to any of the other components of this medicine (listed in section 6) including mouse protein or heparin.

However, in the case of life-threatening thrombotic complications, your doctor will decide whether to continue treatment with CEPROTIN or not.

Warnings and precautions

Consult your doctor before starting treatment with CEPROTIN. Be particularly careful with CEPROTIN if you experience symptoms of an allergic reaction. The symptoms of an allergic reaction include rash, urticaria, difficulty breathing, low blood pressure, chest tightness, and shock. If such symptoms occur during administration of CEPROTIN, the injection should be stopped. These symptoms may constitute an allergic reaction to any of the components, mouse protein, or heparin. The medicine may contain trace elements of heparin and/or mouse protein as a result of the manufacturing process. If such reactions occur, your doctor will decide on the most suitable treatment.

When medicines are prepared from human blood or plasma, certain measures are taken to prevent the transmission of infections to patients. These include careful selection of plasma and blood donors to ensure that those at risk of carrying infections are excluded, and testing of individual donations and plasma pools for signs of virus/infection. The manufacturers of these medicines also include stages in the processing of blood or plasma that can inactivate or eliminate viruses. Despite this, when medicines prepared from human blood or plasma are administered, it is not possible to completely rule out the transmission of infectious diseases. This also applies to unknown or emerging viruses or other possible types of infection.

The measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), and for non-enveloped viruses such as hepatitis A virus. The measures taken may not be sufficient against non-enveloped viruses, such as parvovirus B19. Parvovirus B19 infection can be severe for pregnant women (fetal infection) and for individuals with a weakened immune system or with certain types of anemia (e.g., hemolytic anemia).

Your doctor may recommend appropriate vaccination against hepatitis A and B if you frequently receive human plasma-derived factor VIII.

Using CEPROTIN with other medicines

Currently, no interactions with other medicines are known.

Tell your doctor or pharmacist if you are using or have recently used other medicines, including those obtained without a prescription.

If you switch from oral anticoagulant treatment, treatment with CEPROTIN should continue until the blood level of the oral anticoagulant medicine is adequate and stable.

Using CEPROTIN with food and drinks

Not applicable.

Pregnancy and breastfeeding

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.

Your doctor will decide whether CEPROTIN can be used during pregnancy or breastfeeding.

Driving and using machines

CEPROTIN has no influence on the ability to drive or use machines.

Important information about some of the ingredients of CEPROTIN

Given that the amount of sodium in the maximum daily dose may exceed 200 mg, it may be harmful to individuals on a low-sodium diet.

3. How to use CEPROTIN

CEPROTIN is intended for intravenous administration (infusion into a vein). You will be given CEPROTIN under the close supervision of a doctor with experience in replacement therapy with coagulation factors/inhibitors where monitoring of Protein C activity is possible.

The dosage will vary depending on your condition and body weight.

Dose

The dose, frequency of administration, and duration of treatment depend on the severity of the Protein C deficiency as well as your clinical condition and plasma levels of Protein C. These should be adjusted based on clinical efficacy and laboratory results.

Initially, a Protein C activity of 100% should be achieved and the activity should be maintained above 25% throughout the duration of treatment.

An initial dose of 60 to 80 IU/kg should be administered. Your doctor will take several blood samples to determine how long Protein C stays in your body.

Measurement of Protein C activity using chromogenic substrates for determination of plasma Protein C levels is recommended before and during treatment with CEPROTIN.

The dose should be determined based on the measured laboratory Protein C activity. In the case of acute thrombotic events, determination should be performed every 6 hours until the patient is stabilized, then twice a day, and always immediately before the next injection. It should be taken into account that the half-life of Protein C can be significantly shortened in certain clinical situations such as acute thrombosis with purpura fulminans and skin necrosis.

If you have liver or kidney disease, please inform your doctor, as the treatment may need to be adjusted accordingly.

If you switch to permanent prophylaxis with oral anticoagulants, Protein C replacement should only be discontinued when stable anticoagulation is achieved (see "Important information about some of the components of CEPROTIN").

If you receive prophylactic administration of Protein C, higher trough levels may be required in situations with increased risk of thrombosis (such as infection, trauma, or surgical intervention).

Your doctor may adjust your treatment if you have resistance to activated Protein C, which is a thromboembolic risk factor present in up to 5% of the European population.

Administration

CEPROTIN will be administered to you by intravenous injection after reconstitution of the lyophilized powder for solution for injection with sterile water for injection. It is strongly recommended to record the name and batch number of the product each time you receive a dose of CEPROTIN to maintain a record of the batches used.

Reconstitute the lyophilized powder of CEPROTIN for solution for injection with the supplied solvent (sterile water for injection) using the sterile transfer needle. Gently swirl the vial until all the powder is dissolved.

Once reconstituted, the solution is withdrawn with the sterile filter needle and transferred to a sterile disposable syringe. A new sterile filter needle must be used for each vial of reconstituted CEPROTIN. The solution should be discarded if it contains visible particles.

The reconstituted solution should be administered immediately by intravenous injection.

CEPROTIN should be administered at a maximum injection rate of 2 ml per minute. In children with a body weight below 10 kg, the injection rate should not exceed 0.2 ml/kg/min.

Unused solution, empty vials, and used needles and syringes should be disposed of properly.

The frequency and duration of treatment depend on the severity of your Protein C deficiency, the results of the determination of Protein C levels in your plasma, as well as the location and degree of thrombosis.

In the case of acute thrombosis, CEPROTIN may be administered every 6 hours. As the tendency to form thrombi decreases, the frequency may be reduced.

If you use more CEPROTIN than you should

It is recommended to follow the recommended dose and frequency of administration prescribed by your doctor. If you administer more CEPROTIN than recommended, inform your doctor as soon as possible.

If you forget to use CEPROTIN

Not applicable.

If you stop using CEPROTIN

Do not stop using CEPROTIN without consulting your doctor.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

You may notice some of the following side effects after administration of CEPROTIN:

• As with any medicine administered by intravenous infusion, it is possible (but not seen with CEPROTIN) that allergic reactions may occur, including severe and life-threatening reactions (anaphylaxis). In any case, you should be warned of the initial signs of allergic reactions such as burning and itching at the injection site, chills, flushing, rash, urticaria, difficulty breathing, nausea, headache, lethargy, low blood pressure, and chest tightness.
• The following side effects were observed very rarely during clinical trials (less than 1 case per 10,000 administrations provided to patients): fever (pyrexia), increased C-reactive protein, inflamed patches (urticaria), itching (pruritus), rash, and dizziness.
• In post-marketing experience, restlessness, thoracic hemorrhage, increased sweating, pain, and redness at the injection site have been observed.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly to the Spanish Medicines Agency's Pharmacovigilance System for Human Use: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of CEPROTIN

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 shown.

Store in a refrigerator (2°C - 8°C). Do not freeze. Keep the container in the outer carton in order to protect from light.

The reconstituted solution 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. These measures will help protect the environment.

6. Contents of the pack and other information

Composition of CEPROTIN

Powder:

• The active substance is human Protein C
• The other ingredients are human albumin, sodium chloride, and sodium citrate.2H2O. Solvent: Sterile water for injection.

Appearance and pack contents

CEPROTIN is presented as a powder and solvent for solution for injection and is a white or off-white powder or solid that is easily broken up. After reconstitution, the solution is colorless to slightly yellowish and transparent to slightly opalescent and essentially free of visible particles.

Each pack also contains a transfer needle and a filter needle.

Marketing Authorization Holder and Manufacturer

BAXTER AG

Industriestrasse 67

A-1221 Vienna, Austria

You can obtain further information on this medicine from the local representative of the Marketing Authorization Holder:

Date of last revision of this leaflet:

Detailed information on this medicine is available on the European Medicines Agency website http://www.ema.europa.eu.