Optivate

Package leaflet: Information for the user

Optivate 250 IU, 500 IU, 1000 IU
Powder and solvent for solution for injection
Human blood coagulation factor VIII
Please read all of this leaflet carefully before using this medicine, because it contains
important information for the patient.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, please ask your doctor.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, tell your doctor.

Contents of the leaflet

1. What Optivate is and what it is used for
2. What you need to know 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 Optivate is and what it is used for

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

*Note: The term "j.m." (jednostka miary) has been translated as "IU" (International Units), which is the standard term used in English for biological potency of coagulation factors.

2. Important information before using Optivate

When not to use Optivate:

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

Warnings and precautions

• If bleeding becomes more severe or lasts longer than usual, and if bleeding does not stop after injection of Optivate, consult a doctor. Some patients with factor VIII deficiency may develop inhibitors (antibodies) against factor VIII during treatment. As a result, treatment may not work as expected. The treating physician will regularly order tests to detect possible antibodies, especially before surgical procedures. Both before and after treatment with this medicine, particularly during the first treatment cycle, the doctor will likely order blood tests to check factor VIII levels.
• This medicine may contain small amounts of antibodies against blood group antigens originally present in donor plasma. This is normal and these antibodies usually do not cause problems. However, if high doses of Optivate are required, for example during surgery, and the patient has blood group A, B or AB, the doctor may order blood tests to check whether the medicine affects red blood cells.

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

• careful selection of blood and plasma donors to exclude donors who may carry infections,
• testing of individual blood samples and pooled plasma for the presence of viruses/infections,
• implementation of blood and plasma processing steps that can inactivate or remove viruses.

Despite these measures, it cannot be completely excluded that administration of medicines prepared from human blood or plasma might transmit infection. This also applies to unknown or newly emerging viruses and other types of infections.
These measures are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus, and non-enveloped hepatitis A virus. The effectiveness of these measures may be limited with respect to non-enveloped viruses such as parvovirus B19.
Infection with parvovirus B19 may be dangerous for pregnant women (fetal infection) and for individuals with weakened immune systems or certain types of anemia (e.g. sickle cell or hemolytic anemia).
It is recommended that the name and batch number of the Optivate product be recorded each time before administration to patients, in order to track batches used.
Patients receiving regular or repeated treatment with factor VIII products derived from human plasma may be advised by their doctor to consider vaccination against hepatitis A and B.

Optivate and other medicines
Optivate for injection must not be mixed in the same syringe with other medicines. Inform the doctor about all medicines currently used or recently used, as well as any medicines the patient plans to take.

Pregnancy, breastfeeding and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor before using this medicine.

Driving and operating machinery
The effect of this medicine on the ability to drive or operate machinery is unknown.

3. How to use Optivate

Before injecting the medicine at home, patients will be trained at a hemophilia treatment center
in the administration of the medicine. Only the recommended injection equipment supplied with
the medicine should be used.
This medicine should always be used exactly as prescribed by the doctor. In case of doubt,
consult the doctor.
The doctor will explain what dose to use and when to take the medicine.
The doctor usually specifies the dose in terms of the number of full vials required for the most appropriate
dose. If further treatment is needed, additional doses may be administered every 8, 12 or 24 hours,
depending on requirements. The doctor will provide the patient with information if this is necessary. The table below provides approximate doses of factor VIII required to control bleeding in various
clinical conditions:
Adults:

What dose is required to prevent bleeding in adults?
The usual dose is 20 to 40 IU/kg every 2 or 3 days.
Children
For children under 6 years of age, the doctor will recommend an appropriate dose, but usually
it ranges from 17 to 30 IU/kg. It can be administered up to 3 times per week for bleeding prevention.
Patients who have not been previously treated
The safety and efficacy of Optivate in patients who have not been previously treated have not been established.
When to inject Optivate

• The medicine should be injected at the first signs of bleeding.
• Injections should be repeated as needed until bleeding stops.
• Each bleeding episode should be individually assessed for severity.
• When using the product for the first time, the patient should be supervised by a doctor.

Reconstituting the medicine before use
The medicine must be reconstituted only with the sterile water provided with the product.

1. Optivate must be reconstituted only with water for injections supplied with the product.
2. Before removing the cap, check that the Optivate vial and the container with water supplied with it 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 stopper.
4. Optivate is supplied with the appropriate volume of water for injections, as indicated in the table.

How to reconstitute Optivate
Optivate can be reconstituted using a transfer device called Mix2Vial:
The Mix2Vial transfer device is supplied with the medicinal product to allow easy, safe,
needle-free use.
Preparation of the solution is performed as follows:

	Step 1 Remove the cap from the vial and clean the top of the rubber stopper with an alcohol swab. Repeat this procedure for the vial containing water for injections. Remove the upper part of the transfer device packaging, but leave the device inside the packaging.
	Step 2 Place the blue end of the transfer device onto the water vial and press down until the needle pierces the rubber stopper and clicks into place. Remove the outer plastic packaging from the transfer device and discard it, taking care not to touch the exposed end of the transfer device.
	Step 3 Invert the water vial without removing the transfer device. Place the transparent end of the transfer device onto the product vial and press down until the needle pierces the rubber stopper and clicks into place.
	Step 4 The water for injections will automatically transfer into the product vial due to the vacuum inside. Gently rotate the vial to thoroughly mix the product. Do not shake the vial. Typically, within 2 to 2.5 minutes (maximum 5 minutes), a clear or slightly opalescent solution is obtained.
	Step 5 Separate the empty water vial by detaching the blue part from the transparent part by twisting them counterclockwise. Draw air into an empty syringe by pulling the plunger to the required volume of added water. Attach the syringe to the transparent part of the Mix2Vial™ device. Inject the air from the syringe into the vial.
	Step 6 Immediately invert the vial containing the solution, which will be drawn into the syringe. Detach the filled syringe from the device. The product is now ready for administration. Standard safety procedures for drug administration should be followed. The product should be

Warning: If more than one vial is required to administer the dose, repeat steps 1 to 6 by withdrawing the solution from the vial into the same syringe. The transfer device supplied with the product is sterile and intended for single use only. After completion of the reconstitution process, it should be discarded into a container for contaminated waste.
Do not use this medicine if:

• water is not drawn into the vial containing the medicine (this indicates loss of vacuum in the vial; in such a case, the medicine must not be used)
• during step 6, particles are visible in the syringe, if the solution is cloudy, or if a gel or clot has formed (in such a case, contact Bio Products Laboratory, quoting the batch number printed on the vial).

Use of a higher than recommended dose of Optivate
If an overdose is suspected, stop administration immediately and consult a doctor. If the patient knows that an excessive dose has been administered, they should contact a doctor as soon as possible.
Missing a dose of Optivate
Do not administer a double dose to make up for a missed dose. Inject the normal dose as soon as possible, then continue dosing according to the recommendations of the doctor or haemophilia specialist nurse.
Stopping treatment with Optivate
Before deciding to discontinue treatment, consult your doctor.

4. Possible adverse reactions

Like any medicine, this medicine can cause adverse reactions, although not everyone will experience them.
If any of the following symptoms occur, stop administering the medicine immediately
and contact your doctor or go to the emergency department of the nearest hospital:

• swelling of the throat
• sudden skin redness
• hives
• dizziness (low blood pressure)
• rapid heartbeat
• nausea or vomiting
• restlessness
• chest tightness or wheezing
• tingling

These symptoms may lead to severe shock. The above allergic reactions are very rare (occurring in fewer than 1 in 10,000 treated patients).

Other known adverse reactions include:
Adults and children
Common adverse reactions (may occur in more than 1 in 100 treated patients):

• headache
• sensation that surrounding objects are moving, spinning, or tilting (dizziness)
• cough
• sneezing
• skin redness (rash) or pain at the injection site
• other skin rashes
• limb swelling
• itching
• elevated body temperature (fever)
• sudden chills, feeling cold, followed by rapid temperature rise
• muscle and joint stiffness
• drowsiness, sleepiness, or malaise

If any adverse reactions occur in the patient, you should talk to your doctor. This includes any possible adverse reactions not listed in this leaflet.

Reporting of adverse reactions
If any adverse symptoms occur, including any adverse symptoms not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration 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].
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Optivate

• Do not store at temperatures above 25°C.
• Do not freeze.
• Keep the vial in the outer packaging to protect 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 stated month.
• Do not use this medicine if small particles are observed in the solution. After reconstitution, Optivate should be used within one hour.
• Medicines must not be disposed of via wastewater or household waste. The treatment centre will provide the patient with a special container for the remaining solution, used syringes, needles, and empty vials. This procedure helps protect the environment.

6. Contents of the package and other information

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

What Optivate looks like and contents of the pack
Optivate is a white or pale yellow powder available in 250 IU (international units), 500 IU or 1000 IU contained in glass vials. The vials are sealed under vacuum with a halobutyl rubber stopper, protected with a polypropylene cap and an aluminium seal.
Optivate must be reconstituted only with the water for injections supplied with Optivate in clear glass bottles.
A transfer device called Mix2Vial is also included with the medicine, allowing easy and safe reconstitution of the product without using a needle.

Marketing Authorisation Holder and Manufacturer
Bio Products Laboratory Limited, Dagger Lane, Elstree, Hertfordshire, WD6 3BX, United Kingdom.

This medicinal product is authorised in the European Economic Area countries 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

March 2017
For additional information, please contact BPL via the Marketing Department at the address below or by email at [email protected].
Bio Products Laboratory Limited,
Dagger Lane,
Elstree,
Hertfordshire,
WD6 3BX, United Kingdom.