Coagadex

Patient Information Leaflet

Coagadex 250 IU powder and solvent for solution for injection, 500 IU powder and solvent for solution for injection

human coagulation factor X
Please read all of this leaflet carefully before you use this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it may be harmful.
• If any adverse reaction occurs, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What Coagadex is and what it is used for

Coagadex is a human coagulation factor X concentrate, a protein necessary for blood clotting. The factor X in Coagadex is extracted from human plasma (the liquid part of the blood). It is used to treat and prevent bleeding in patients with congenital factor X deficiency, including during surgical procedures.
Patients with factor X deficiency do not have enough factor X to allow blood to clot properly, which leads to excessive bleeding. Coagadex replaces the missing factor X, enabling blood to clot normally.

2. What you should know before using Coagadex

Do not use Coagadex:

• if you are allergic to human coagulation factor X or to any of the other ingredients of this medicine (listed in section 6). Please check with your doctor if this applies to you.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Coagadex:

• if you have bleeding that is heavier or longer than usual and does not stop after an injection of Coagadex;
• if you are taking a medicine to prevent blood clotting that works by blocking coagulation factor Xa. These medicines may interfere with the action of Coagadex.

Some patients with factor X deficiency may develop inhibitors (antibodies) against factor X during treatment. This means that the treatment may not work properly. Your doctor will regularly monitor for the development of these antibodies, especially before surgery. Both before and after treatment with this medicine, particularly during the first treatment cycle, your doctor will likely perform tests to monitor your blood factor X levels.

Viral safety
When medicines are manufactured from human blood or plasma, several safety measures are applied to prevent transmission of infections to recipients. These include:

• careful selection of plasma and blood donors to ensure potential carriers of infections are excluded;
• testing of donated plasma to detect the presence of viruses and infections;
• application of processing procedures that inactivate or remove viruses.

The measures taken are considered effective against the following viruses: human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, hepatitis A virus, and parvovirus B19. Despite these measures, whenever medicines prepared from human blood or plasma are administered, the possibility of transmitting an infection cannot be completely ruled out. This also applies to unknown or emerging viruses or other types of infections.

Each time you receive a dose of Coagadex, it is strongly recommended to record the name and batch number of the medicine in order to keep track of the batches used.

Your doctor may recommend that you consider vaccination against hepatitis A and B if you regularly receive multiple doses of medicines containing factor X derived from human plasma.

Children and adolescents
The warnings and precautions listed for adults also apply to children (aged 2 to 11 years) and adolescents (aged 12 to 18 years).

Other medicines and Coagadex
Tell your doctor if you are taking, have recently taken, or might take any other medicines.

Pregnancy, breast-feeding and fertility
If you are pregnant, think you might be pregnant, are planning to become pregnant, or are breast-feeding, please consult your doctor or pharmacist before using this medicine.

Driving and using machines
No effects of this medicine on the ability to drive or operate machinery are known.

Coagadex contains sodium
This medicine contains up to 9.2 mg of sodium (a main component of table salt) per millilitre of solution. This corresponds to 0.0046% of the maximum daily recommended dietary intake of sodium for an adult.

3. How to use Coagadex

Treatment must be initiated by a physician experienced in the treatment of bleeding disorders.
Use this medicine exactly as directed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Coagadex must be injected directly into a vein. Before injecting the medicine at home, you must
have received training from a healthcare professional on how to do it.
Your doctor will explain how much medicine you should use, when to use it, and for how long.
Your doctor will usually indicate your dose in terms of the number of full vials corresponding to the most appropriate dose for you. Do not administer more than 60 UI/kg per day at any age.

Use in adults
What dose of Coagadex should be administered for the treatment of bleeding or to
prevent further bleeding?
Your doctor will determine the dose of Coagadex needed to treat bleeding and to prevent further episodes; the required dose depends on the normal level of factor X in the blood.

What is the dose administered before, during, and after major surgery?
Before: The dose of Coagadex used should be sufficient to increase factor X levels in the blood to between 70 and 90 units/dL. The necessary dose for your case will depend on your normal factor X blood level and will be calculated by your doctor.
After: During the first few days after surgery, plasma factor X concentration will be monitored regularly. It is recommended to maintain factor X levels in the blood above 50 units/dL. The required dose will be determined by your doctor.

If the blood concentration of factor X is too low (this value will be tested by your doctor) or decreases more rapidly than expected, a factor X inhibitor may be present, which prevents the medicine from working properly. Your doctor will arrange appropriate laboratory tests to determine if this is the case.

What is the regularly administered dose for long-term prevention of bleeding?
Your doctor will advise whether this applies to your case and, if so, will determine the appropriate dose.

Use in children and adolescents
Your doctor will recommend a dose suitable for you or your child. Doses for children under 12 years of age are generally higher than those for adolescents and adults. Doses for adolescents will be similar to those for adults.

When to inject Coagadex

• The medicine should be injected at the first sign of bleeding.
• The injection should be repeated, if necessary, to stop the bleeding.
• Each individual's bleeding episode must be assessed based on its actual severity.
• If you are using the medicine for the first time, your doctor will monitor you.

Reconstituting the medicine before use
The medicine must be reconstituted only with the solvent provided with it.

Coagadex is supplied with the amount of solvent indicated in the table.
This medicine can be reconstituted using the needle-free Mix2Vial transfer device included in each package.
Bring the Coagadex containers to room temperature before mixing.
Prepare the medicine as follows:

Step 1

• Remove the cap from the powder vial and clean the top of the stopper with an alcohol swab.
• Repeat this procedure with the solvent vial.
• Pull off the top part of the transfer device, leaving the device in the package.

Step 2

• Place the blue end of the transfer device onto the solvent vial and push down until the spike pierces the rubber stopper and locks securely in place.
• Remove the outer plastic packaging from the transfer device and discard it, taking care not to touch the exposed end of the device.

Step 3

• Turn the solvent vial upside down with the device still attached.
• Place the transparent end of the transfer device onto the powder vial and push down until the spike pierces the rubber stopper and locks securely in place.

Step 4

• The solvent will be drawn into the powder vial by vacuum.
• Gently rotate the vial to ensure the powder is completely dissolved. Do not shake the vial.
• The resulting solution, usually within about 1 minute (maximum 5 minutes), should be colorless, clear or slightly opalescent.

Step 5

• Detach the empty solvent vial and the blue part of the transfer device from the transparent part by unscrewing counterclockwise.
• Take an empty syringe (not provided in the Coagadex package) and draw air into the syringe by pulling the plunger to the volume corresponding to the water added in step 4.
• Attach the syringe to the transparent end of the transfer device and push the air from the syringe into the vial.

Step 6

• Immediately invert the solution vial, which will draw the solution into the syringe.
• Disconnect the filled syringe from the transfer device.
• The medicine is now ready for use. Follow standard safety procedures for administration. Ensure that the medicine is used within one hour of reconstitution.

Do not use this medicine:

• if the solvent is not drawn into the vial (this indicates loss of vacuum in the vial, and therefore the powder must not be used).
• if the dissolved powder and solvent form a gel or a clot (if this occurs, inform medical personnel, quoting the batch number shown on the vial).

If you use more Coagadex than you should
If you administer more of this medicine than prescribed by your doctor, you may develop a blood clot. If you think you have administered too much, stop the injection and consult your doctor, pharmacist, or nurse. If you know you have taken an excessive amount, consult your doctor, pharmacist, or nurse as soon as possible.

If you forget to use Coagadex
Do not use a double dose to make up for the missed dose. Inject the normal dose as soon as you remember, then continue with the dosing schedule as directed by your doctor.

If you stop treatment with Coagadex
Always consult your doctor before deciding to stop treatment.

If you have any questions 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.
Allergic reactions (hypersensitivity reactions) have rarely occurred during treatment of bleeding disorders with similar medicines (affecting up to 1 in 1,000 people), sometimes progressing to shock. Signs of allergic reactions may include rash (including urticaria), tingling, hot flushes, nausea, vomiting, headache, cough, wheezing, tightness of the chest, chills, rapid heartbeat, dizziness, drowsiness, restlessness, swelling of the face, throat tightness, and injection site discomfort.
If you experience any of the side effects listed above, consult your doctor.
The following side effects have been reported with Coagadex.
Common (may affect up to 1 in 10 people):

• pain or redness at the injection site
• fatigue
• back pain

Side effects in children and adolescents
Side effects in children are similar to those in adults.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, consult your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Coagadex

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the container after "Exp.". The expiry date refers to the last day of that month.
Do not store above 30°C.
Do not freeze.
Keep the vial in the outer packaging to protect the medicine from light.
Do not use this medicine if you notice small particles in the reconstituted solution. Once prepared, Coagadex must be used within one hour.
Do not dispose of any medicine via wastewater or household waste. Your treatment centre will provide you with a special container for the disposal of any remaining solution, syringes, needles, and empty containers used. This will help protect the environment.

6. Package contents and other information

What Coagadex contains

• The active substance is human coagulation factor X. One vial contains nominally 250 IU or 500 IU of human coagulation factor X.
• The other excipients are: citric acid, disodium phosphate dihydrate, sodium chloride, sodium hydroxide and sucrose (see section 2 for further information on excipients).
• Solvent: water for injections.

Description of the appearance of Coagadex and contents of the pack
Coagadex is a white or almost white powder available in 250 IU and 500 IU pack sizes. After reconstitution, the solution is colourless, clear or pearly (opalescent). Before injection, inspect the solution. Do not use if the solution is cloudy or contains particles.
A transfer device called Mix2Vial is also provided.

250 IU pack contents
1 vial containing 250 IU of powder
1 vial containing 2.5 mL of water for injections
1 transfer device (Mix2Vial)

500 IU pack contents
1 vial containing 500 IU of powder
1 vial containing 5 mL of water for injections
1 transfer device (Mix2Vial)

Not all pack sizes may be marketed.

Marketing Authorisation Holder
Kedrion S.p.A. - Loc. Ai Conti, 55051 Castelvecchio Pascoli, Barga (Lucca), Italy.

Manufacturer
PharmaKorell GmbH, Georges-Köhler-Str. 2, 79539 Lörrach, Germany

For further information on this medicinal product, contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien                                             Lietuva
Kedrion S.p.A.                                                                 Kedrion S.p.A.
Tél/Tel: +39 0583 767507                                             Tel: +39 0583 767507
e-mail: [email protected]                                     e-mail: [email protected]
(Italie/Italië/Italien)                                                     (Italija)

България                                                                    Luxembourg/Luxemburg
Kedrion S.p.A.                                                                 Kedrion S.p.A.
Teл.: +39 0583 767507                                                 Tél/Tel: +39 0583 767507
e-mail: [email protected]                                     e-mail: [email protected]
(Италия)                                                                         (Italie/Italien)

Česká republika                                                         Magyarország
Kedrion S.p.A.                                                                 Kedrion S.p.A.
Tel: +39 0583 767507                                                 Tel: +39 0583 767507
e-mail: [email protected]                                     e-mail: [email protected]
(Itálie)                                                                            (Olaszország)

Danmark                                                                     Malta
Kedrion S.p.A.                                                                 Kedrion S.p.A.
Tfl: +39 0583 767507                                                 Tel: +39 0583 767507
e-mail: [email protected]                                     e-mail: [email protected]
(Italien)                                                                         (l-Italja)

Deutschland                                                               Nederland
Kedrion S.p.A.                                                                 Kedrion S.p.A.
Tel: +39 0583 767507                                                 Tel: +39 0583 767507
e-mail: [email protected]                                     e-mail: [email protected]
(Italien)                                                                         (Italië)

Eesti                                                                            Norge
Kedrion S.p.A.                                                                 Kedrion S.p.A.
Tel: +39 0583 767507                                                 Tlf: +39 0583 767507
e-mail: [email protected]                                     e-mail: [email protected]
(Itaalia)                                                                         (Italia)

Ελλάδα                                                                         Österreich
Kedrion S.p.A.                                                                 Kedrion S.p.A.
Τηλ: +39 0583 767507                                                 Tel: +39 0583 767507
e-mail: [email protected]                                     e-mail: [email protected]
(Ιταλία)                                                                            (Italien)

España                                                                         Polska
Kedrion S.p.A.                                                                 Kedrion S.p.A.
Tel: +39 0583 767507                                                 Tel.: +39 0583 767507
e-mail: [email protected]                                     e-mail: [email protected]
(Italia)                                                                            (Włochy)

France                                                                         Portugal
Laboratoire Cevidra                                                     Kedrion S.p.A.
Tel: +33 493705831                                                     Tel: +39 0583 767507
e-mail: [email protected]                                     e-mail: [email protected]
France                                                                             (Itália)

Hrvatska                                                                     România
Kedrion S.p.A.                                                                 Kedrion S.p.A.
Tel: +39 0583 767507                                                 Tel: +39 0583 767507
e-mail: [email protected]                                     e-mail: [email protected]
(Italija)                                                                            (Italia)

Ireland                                                                         Slovenija
Kedrion S.p.A.                                                                 Kedrion S.p.A.
Tel: +39 0583 767507                                                 Tel: +39 0583 767507
e-mail: [email protected]                                     e-mail: [email protected]
(Italy)                                                                             (Italija)

Ísland                                                                            Slovenská republika
Kedrion S.p.A.                                                                 Kedrion S.p.A.
Sími: +39 0583 767507                                                 Tel: +39 0583 767507
Netfang: [email protected]                                 e-mail: [email protected]
(Ítalíu)                                                                            (Taliansko)

Italia                                                                             Suomi/Finland
Kedrion S.p.A.                                                                 Kedrion S.p.A.
Tel: +39 0583 767507                                                 Puh/Tel: +39 0583 767507
e-mail: [email protected]                                     e-mail: [email protected]
Italia                                                                                (Italia)

Κύπρος                                                                         Sverige
Kedrion S.p.A.                                                                 Scandinavian Biopharma Distribution AB
Τηλ: +39 0583 767507                                                 Tel: +46 (0)8 470 56 00
e-mail: [email protected]                                     E-mail: [email protected]
(Ιταλία)                                                                            Sverige

Latvija
Kedrion S.p.A.
Tel: +39 0583 767507
e-mail: [email protected]
(Itālija)

More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu