Optivate

Package Leaflet: Information for the User

Optivate 250 IU, 500 IU, 1000 IU

Powder and solvent for solution for injection

Human coagulation factor VIII

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

• Keep this package leaflet, you may need to read it again.
• If you have any further questions, ask your doctor.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this package leaflet, please inform your doctor.

Table of Contents of the Package Leaflet

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

1. What is Optivate and what is it used for

Optivate is a highly purified concentrate of human coagulation factor VIII obtained from human plasma from screened donors. It is a white or pale yellow sterile powder, supplied with water for injections. Optivate is administered by intravenous injection for the prevention and treatment of bleeding in patients with hemophilia A (congenital factor VIII deficiency in the blood). Your doctor may explain in more detail why this medicine has been prescribed for you.

2. Important information before using Optivate

When not to use Optivate:

• if you are allergic (hypersensitive) to human coagulation factor VIII or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

• In case of more severe or prolonged bleeding than usual, and if the bleeding does not stop after injection of Optivate, consult your doctor. In some patients with factor VIII deficiency, inhibitors (antibodies) against factor VIII may develop during treatment. As a result, the treatment may not work as it should. Your treating doctor will regularly order tests to detect any antibodies, especially before surgery. Both before and after the end of treatment with this medicine, especially during the first treatment cycle, your doctor will likely order tests to check the level of factor VIII in the blood.
• This medicine may contain small amounts of antibodies against blood group antigens originally present in the donors' plasma. This is normal and in most cases, these antibodies do not cause any problems. However, if large doses of Optivate are to be administered, for example during surgery, and the patient has blood group A, B, or AB, the doctor may order a blood test to check if the medicine affects red blood cells.

Complications related to catheterization: if it is necessary to use a device that provides access to the central vein (CVAD, central venous access device), consider the risk of complications associated with the use of CVAD, including local infections, bacteremia, and thrombosis at the catheter insertion site. For medicines produced from human blood or plasma, certain measures are taken to prevent the transmission of infections to patients. These measures include:

• careful selection of blood and plasma donors to ensure the exclusion of donors who may be carriers of infections,
• testing of individual blood samples and plasma pools for the presence of viruses/infections,
• use of blood and plasma processing stages that can inactivate or remove viruses.

Despite these measures, it cannot be completely ruled out that infectious agents may be transmitted during the administration of medicines prepared from human blood or plasma. This also applies to unknown or newly discovered viruses and other types of infections. The measures taken are considered effective against enveloped viruses, such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, as well as non-enveloped hepatitis A virus. The effectiveness of these measures may be limited for non-enveloped viruses, such as parvovirus B19. Parvovirus B19 infection can be hazardous for pregnant women (fetal infection) and for individuals with weakened immune systems or with certain types of anemia (e.g., sickle cell or hemolytic). It is recommended that before each administration of a dose of Optivate to the patient, the name and batch number of the product be recorded for the purpose of registering the batches used. Patients who regularly or repeatedly receive products containing factor VIII from human plasma may be advised by their doctor to consider vaccination against viral hepatitis A and B.

Optivate and other medicines

Optivate should not be mixed in the same syringe with other medicines. Tell your doctor about all medicines you are taking or have recently taken, as well as any medicines you plan to take.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, consult your doctor before using this medicine.

Driving and using machines

The effect of this medicine on the ability to drive and use machines is not known.

3. How to use Optivate

Before injecting the medicine at home, patients will be trained at a hemophilia treatment center on how to administer the medicine. Only the recommended injection equipment provided with the medicine should be used. This medicine should always be used exactly as your doctor has told you. If you are not sure, ask your doctor. Your doctor will explain what dose to use and when to take the medicine. The doctor usually prescribes a dose in relation to the number of whole vials for the most suitable dose. If further treatment is needed, subsequent doses can be administered every 8, 12, or 24 hours, depending on the needs. Your doctor will provide you with information if necessary. The following table shows the approximate doses of factor VIII needed to stop bleeding in different disease states:

Adults:

What dose is needed to prevent bleeding in adults?

Usually, a dose of 20 to 40 IU/kg every 2 or 3 days is sufficient.

Children

In children under 6 years of age, the doctor will recommend the appropriate dose, but it usually ranges from 17 to 30 IU/kg. It can be administered up to 3 times a week to prevent bleeding.

Patients who have not been previously treated

The safety and efficacy of the Optivate medicinal product have not been established in patients who have not been previously treated.

When to inject Optivate

• The medicine should be injected after the first symptoms of bleeding appear.
• Injections should be repeated as needed until the bleeding stops.
• Each bleeding episode should be evaluated individually in terms of severity.
• In case of first-time use of the product, the doctor should supervise the patient.

Dissolving the medicine before use

The medicine should be dissolved onlyin the sterile water for injections provided with the product.

• 1. Optivate should be dissolved only in the water for injections provided with the product.
• 2. Before removing the cap, check that the Optivate vial and the supplied water vial are at room temperature (between 20°C and 30°C).
• 3. The water for injections intended for use with Optivate is supplied in a glass vial with a rubber stopper.
• 4. Optivate is supplied with the appropriate amount of water for injections, as presented in the table.

How to dissolve Optivate

The medicine can be dissolved using a transfer system called Mix2Vial:

The Mix2Vial transfer system is provided with the medicine to enable easy, safe use without the need for a needle. Preparation of the solution is as follows:

	Step 1 Remove the cap from the vial and wipe the top of the rubber stopper with an alcohol swab. Repeat this step for the water vial. Remove the top part of the Mix2Vial packaging, but leave it in the packaging.
	Step 2 Place the blue end of the Mix2Vial system on the water vial and press until the needle pierces the rubber stopper, until it clicks. Remove the outer plastic packaging from the Mix2Vial system and discard it, being careful not to touch the exposed end of the Mix2Vial system.
	Step 3 Turn the water vial upside down without removing the Mix2Vial system from it. Place the transparent end of the Mix2Vial system on the Optivate vial and press until the needle pierces the rubber stopper, until it clicks.
	Step 4 The water for injections will automatically flow into the Optivate vial due to the vacuum in the vial. Gently rotate the vial to mix the product thoroughly. Do not shake the vial. Usually, within 2 to 2.5 minutes (maximum 5 minutes), a clear or slightly pearl-colored solution is obtained.
	Step 5 Separate the empty water vial and the blue part from the transparent part by twisting them in the opposite direction of the clock hands. Draw air into the empty syringe by pulling the plunger to the required volume of added water. Attach the syringe to the transparent part of the Mix2Vial system. Inject air from the syringe into the vial.
	Step 6 Immediately turn the vial with the solution upside down and draw the solution into the syringe. Detach the filled syringe from the Mix2Vial system. The product is now ready for administration. Follow the usual safety procedures when administering the medicine. The product should be

Warning:If more than one vial of the product is needed to administer the dose, repeat steps 1 to 6 by drawing the solution from the vial into the same syringe. The Mix2Vial system provided with the product is sterile and intended for single use. After completing the dissolution process, dispose of it in a container for contaminated items. Do not use this medicine if:

• the water does notflow into the vial with the medicine (this means that the vacuum in the vial is lost; in this case, do notuse the medicine)
• if during step 6, there are any particles in the syringe, if the solution is cloudy, or if a gelor clotforms (in this case, inform Bio Products Laboratory, providing the batch number printed on the vial).

Using more than the recommended dose of Optivate

If you suspect that the dose of Optivate is too high, stop the injection and consult your doctor. If you know that you have taken too much of the medicine, contact your doctor as soon as possible.

Missing a dose of Optivate

Do not take a double dose to make up for a forgotten dose. Take the normal dose as soon as possible and then continue dosing as recommended by your doctor or nurse specialized in hemophilia treatment.

Stopping treatment with Optivate

Beforestopping treatment, consult your doctor.

4. Possible side effects

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

If you experience any of the following symptoms, stop the injection immediately and inform your doctor or go to the emergency room of the nearest hospital:

• throat swelling
• sudden skin redness
• hives
• dizziness (low blood pressure)
• rapid heartbeat
• nausea or vomiting
• restlessness
• chest tightness or wheezing
• tingling. These symptoms can lead to severe shock. The above allergic reactions are very rare(occurring in less than 1 in 10,000 treated patients).

Other known side effects include:

Adults and children

Common side effects (may affect more than 1 in 100 treated patients):

• headache
• feeling that objects around are moving, spinning, or tilting (dizziness)
• cough
• sneezing

• skin redness (rash) or pain at the injection site
• other skin rash
• limb swelling
• itching
• increased body temperature (fever)
• sudden chills, feeling cold, and rapid temperature rise
• muscle and joint stiffness
• drowsiness, lethargy, or malaise

If you experience any side effects, talk to your doctor. This includes any possible side effects not listed in this package leaflet.

Reporting side effects

If you experience any side effects, including those not listed in this package leaflet, please inform 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, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, e-mail: [email protected]. 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 Optivate

• Do not store above 25°C.
• Do not freeze.
• Store the vial in the outer packaging to protect it from light.
• Keep the medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the month stated.
• Do not use this medicine if you notice small particles in the solution. After dissolution, Optivate should be used within 1 hour.
• Medicines should not be disposed of via wastewater or household waste. The treatment center will provide you with a special container for the remains of the solution, used syringes, needles, and empty containers. This will help protect the environment.

6. Contents of the pack and other information

What Optivate contains

The active substance is human coagulation factor VIII. The other ingredients are sodium chloride, calcium chloride, sodium citrate, polysorbate 20, sodium hydroxide (for pH adjustment), hydrochloric acid (for pH adjustment), and trehalose. The preparation contains human von Willebrand factor (Von Willebrand factor, VWF).

What Optivate looks like and what the pack contains

Optivate is a white or pale yellow powder with a content of 250 IU (International Units), 500 IU, or 1000 IU in glass vials. The vials are closed under vacuum with a rubber stopper, secured with a polypropylene cap and an aluminum seal. Optivate should be dissolved only with the water for injections provided with the Optivate medicine in transparent glass vials. A transfer system called Mix2Vial is also provided with the medicine to enable easy and safe dissolution of the product without the need for a needle.

Marketing authorization holder and manufacturer

Bio Products Laboratory Limited, Dagger Lane, Elstree, Hertfordshire, WD6 3BX, United Kingdom.

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Austria, Cyprus, Czech Republic, Estonia, Germany, Hungary, Ireland, Latvia, Lithuania, Malta, Netherlands, Poland, Portugal, Romania, Slovakia, United Kingdom: Optivate Belgium: Optiwate.

Date of last revision of the package leaflet:

March 2017 For further information, contact BPL through the Marketing Department at the following address or at [email protected]. Bio Products Laboratory Limited, Dagger Lane, Elstree, Hertfordshire, WD6 3BX, United Kingdom.