Package Leaflet: Information for the User    optgenls

OPTIVATE® 250 IU, 500 IU, 1000 IU POWDER FOR SOLUTION FOR INJECTION HIGH PURITY FACTOR VIII AND VON WILLEBRAND FACTOR CONCENTRATE

Please read all of this leaflet carefully before you start using this medicine.

•    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 you personally. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

•    If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

In this leaflet:

1.    What Optivate is and what it is used for

2.    Before you use Optivate

3.    How to use Optivate

4.    Possible side effects

5.    How to store Optivate

6.    Further information

1.    WHAT OPTIVATE IS AND WHAT IT IS USED FOR

Optivate is a high purity factor VIII and von Willebrand Factor concentrate from human blood plasma obtained from screened donors.

It is a white sterile powder, supplied with sterile water (Sterilised Water for Injections, Ph.Eur.). Optivate is given by injection into a vein (intravenously) and is used to prevent and treat bleeding in patients with Haemophilia A (congenital factor VIII deficiency in the blood). Your doctor will explain further why this medicine has been given to you.

2.    BEFORE YOU USE OPTIVATE

Do not use this medicine and speak to your doctor if you think you could be allergic (hypersensitive) to the active substance(s) or to any of the other ingredients (See section 6 for a list of these).

•    Your doctor will advise you as to which vaccinations you should be given as a routine precaution, because you are receiving a blood plasma product.

Blood Tests

•    If you have a larger or longer bleed than usual and the bleeding does not stop after an injection of Optivate, speak to your doctor.

Some patients with a shortage of factor VIII may develop inhibitors (antibodies) to factor VIII during treatment. This could mean that the treatment will not work properly. Your doctor will check regularly for the development of these antibodies, and especially before an operation.

Both before and after treatment with this medicine, particularly for your first course of treatment, your doctor will probably carry out tests to check the level of factor VIII in your blood.

•    This medicine may contain small amounts of blood group antibodies originally present in the plasma from the donors. This is normal and, in most cases, these antibodies do not cause any problems. However, if you need large doses of Optivate, for example during surgery, and are blood group A, B, or AB, your doctor may need to do a blood test to check if the medicine has had any effect on your red blood cells.

Taking other medicines

These injections must not be mixed with other medicinal products in the same syringe.

Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Pregnancy and breast-feeding

If you are pregnant, think you may be pregnant or are breast-feeding, tell your doctor. Your doctor will tell you if this product is necessary for you to take at this time.

Driving and using machines

There are no known effects of this product on the ability to drive or operate machinery.

Please note:

When medicines are made from human blood or plasma, certain measures are put in place to prevent infections being passed on to patients. These include careful selection of blood and plasma donors to make sure those at risk of carrying infections are excluded, and the testing of each donation and pools of plasma for signs of virus/infections. Manufacturers of these products also include steps in the processing of the blood or plasma that can inactivate or remove viruses. Despite these measures, when medicines prepared from human blood or plasma are administered, the possibility of passing on infection cannot be totally excluded. This also applies to any unknown or emerging viruses or other types of infections.

The measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus and hepatitis C virus and for the non-enveloped hepatitis A and parvovirus B19 viruses.

It is strongly recommended that every time you receive a dose of Optivate, the name and batch number of the product are recorded in order to maintain a record of the batches used.

3. HOW TO USE OPTIVATE

Before injecting this medicine at home, you will have received training at your Haemophilia Centre on how to do so.

Use only the recommended injection equipment provided with your medicine.

How much Optivate to give

Always use this medicine exactly how your doctor has told you. You should check with your doctor if you are not sure.

•    Your doctor will explain to you how much you should use and when you should use it.

•    Your doctor will usually tell you your dose in terms of the number of full vials nearest to the dose most suited to you.

•    If further treatment is needed, doses may be repeated at intervals of 8, 12 or 24 hours, as required. Your doctor will advise you if this is necessary.

The table gives the approximate doses of factor VIII which are needed to stop bleeding in various conditions:

Adults

Condition	Initial dose of Optivate (IU/kg body weight)
Minor spontaneous bleeding in joints and muscles.	8 - 16
Severe bleeding in joints and muscles, haematoma (swelling caused by collection of blood) in potentially serious situations, blood in the urine.	12 - 24
Major surgery.	See below

How much do adults require to prevent bleeding?

20 to 40 IU/kg every 2 or 3 days is usually enough.

Children

For children under the age of 6 years, your doctor will recommend the appropriate dose but the usual dose is 17 to 30 IU/kg. This can be given up to 3 times a week for prevention of bleeding.

When to inject Optivate

•    The medicine should be injected when the first sign of bleeding occurs.

•    The injection should be repeated as necessary to stop the bleeding.

•    Each individual bleed should be judged on its own severity.

•    If you are using this product for the first time, your doctor will supervise you.

Dissolving your medicine before use

Your medicine must only be dissolved in the sterile water provided with the product.

Quantity of Optivate	Quantity of Water
250 IU	2.5 mL
500 IU	5 mL
1000 IU	10 mL

1.    Before you remove the “flip-off” top, make sure that the vial of Optivate and the container of water supplied with it are both at room temperature (between 20°C and 30°C).

2.    Sterile water for use with Optivate is provided in an ampoule with a “snap-off” cap or a glass vial with a stopper.

3.    Keep all injection equipment sterile.

4.    Do not use any solution if any small bits can be seen in the vials.

There are two ways of continuing to make up the Optivate for injection by the use of a filter needle or Mix2Vial device - only one of

these options will be provided in your pack. Ensure the correct method below is utilised for the transfer device supplied:

Using the Filter Needle (where supplied):

1.    If the Water for Injections is in a plastic ampoule, break open the top and draw up the volume of water needed with a sterile needle and syringe (not the filter needle).

2.    If the Water for Injections is in a glass vial remove the “flip-off” top and clean the top of the stopper with an alcohol swab.

3.    If using a double spiked needle (only for use with the correct volume of water for injection in glass vials), remove the cover guard from one end of the double-ended transfer needle (which your doctor can provide) and insert the needle through the stopper into the vial of water.

4.    Remove the other end of the needle guard, turn it upside down over the vial of Optivate and push the needle through the Optivate stopper..

5.    On piercing the stopper of the Optivate vial, the water will be drawn in as the vial is sealed under vacuum. A small amount of water will remain in the water vial, which can be discarded. Continue from point 8 below

6.    If using a transfer needle, transfer the water to the vial of Optivate by pushing the needle through the stopper of the vial. The water in the syringe will be drawn into the vial, which is under vacuum, so there is no need to push the plunger of the syringe. Note: The filter needle provided must not be used to draw up the Water for Injections.

7.    Gently swirl the Optivate vial (do not shake) and then remove the syringe from the needle to release the vacuum in the vial.

8.    Continue to swirl the Optivate vial gently until the powder is dissolved (usually in about 2 to 21/2 minutes).

9.    When dissolved, draw up the solution using the filter needle attached to a syringe. Use a new filter needle for each vial of Optivate if your dose is more than one vial.

10.    Disconnect the filter needle from the syringe.

11.    The product is now ready for administration. Follow the normal safety practices for administration. Use the product immediately after reconstitution, the product must not be stored.

Using the Mix2Vial (where supplied):

The Mix2Vial^TM Transfer Device is provided with your product for needle-free, easy and safe use.

The reconstitution is performed as follows:

Note: If you have to use more than one vial to make up your required dose, repeat Steps 1 to 6 withdrawing the solution in the vial into the same syringe. The Transfer Device supplied with your product is sterile and cannot be used more than once. When the reconstitution process is complete dispose of in your ‘sharps box’.

Do not use this medicine if:

•    the water is not pulled into the product vial (this indicates a loss of vacuum in the vial, so the product must not be used).

•    the dissolved product and Sterilised Water for Injections forms a gel or a clot (if this happens, please tell Bio Products Laboratory Limited, reporting the batch number printed on the vial). Do not use solutions which are cloudy or have bits in them.

Injecting the medicine

After the medicine is dissolved inject the medicine and attach a suitable needle to the syringe.

The dose, especially your first, should be given slowly (no more than 3 mL per minute) into your vein.

Remember

-    the solution must not be stored after reconstitution.

-    you must finish injecting the dose into a vein within one hour of dissolving the medicine.

-    the solution must not be added to any other fluids, blood or any other medicine.

-    you should only use the sterile water supplied to make up the solution. Never inject the water on its own, without first dissolving the powder in it.

How much is given before, during and after major surgery?

1.    Major surgery should only be performed when levels of factor VIM can be tested.

2.    Your blood should be tested for factor VI11 inhibitors (antibodies).

3.    If antibodies are not present, a dose of 32 to 40 IU per kg of body weight is given before the operation.

4.    During the first few days after the operation, the plasma factor VIII concentration is usually checked at regular periods.

5.    A dose of Optivate is usually given every 8 to 24 hours, as needed.

6.    After the first few days, the number of times the dose is given may be reduced.

7.    Treatment will be continued for as long as recommended by your doctor.

8.    If the factor VIII concentration does not reach the expected level (this will be tested by your doctor), or if it decreases quicker than expected (within 12 hours), an inhibitor to factor VIII may be present, which stops factor VIII from working properly. Your doctor is likely to have the appropriate laboratory tests done to see if there is such an inhibitor present.

If you use more Optivate than you should

If you think you may be using too much, stop the injection and tell your doctor. If you know you have used too much, tell your doctor as soon as possible.

If you forget to use Optivate

Do not use a double dose to make up for a forgotten dose. Inject your normal dose as soon as you remember and then continue as instructed by your doctor or Haemophilia nurse.

If you stop using Optivate

Always consult your doctor before deciding to stop your treatment.

4. possible side effects

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

Stop the infusion and tell your doctor immediately or go to the emergency department of your nearest hospital, if you get any of the following symptoms:

•    Swelling around the throat    • Feeling lightheaded or dizzy (low blood pressure)

• Flushing    • Rapid heart beat

•    Hives (nettle rash)

These symptoms may worsen into severe shock. The above allergic-type reactions are very rare (fewer than 1 patient in every 10,000 patients treated get them).

•    Feeling sick or being sick    • Tightness in the chest or wheezing

• Restlessness    • Tingling sensation

Other known side effects are:

Adults and Children

Common (more than 1 in every 100 patients treated):

•    Headache    • Swelling in the extremities of the body

•    Other skin rashes    • Itching

•    Feeling that everything is moving, spinning round or tilting (vertigo) • Raised temperature (fever)

•    Cough    • Sudden shivering and feeling cold and rapid rise in temperature

•    Sneezing    • Stiffness in muscles and joints

•    Redness of the skin (rashes) or pain at the    • Sleepiness, lethargy or feeling unwell

place where the medicine was injected

5.    how to store optivate

•    Keep out of the reach and sight of children.

•    You should store the powder in its container and carton, in the dark, either in a refrigerator or at room temperature (2°C to 25°C), but no higher. Do not freeze.

•    The vial of sterilised water that comes with the medicine should also be stored, either in a refrigerator or at room temperature, (up to 25°C, but no higher). Do not freeze.

•    Neither the medicine nor the water should be used after the expiry date which is stated as “EXPIRY” on the containers. The expiry date refers to the last day of that month.

•    Do not use any solution if any small bits can be seen in it.

•    Once reconstituted, Optivate must be used within one hour.

Disposal

After injection of the correct dose, dispose of any solution that remains, any used syringes and needles and empty containers. Your treatment centre will provide a special container (‘sharps box’) for this purpose. Medicines should not be disposed of via wastewater or household waste.

6.    further information

What Optivate contains Powder

The active substances are human coagulation factor VIM with associated von Willebrand Factor (VWF), the natural stabiliser for factor VIM. The other ingredients are: sodium chloride, calcium chloride, sodium citrate, polysorbate 20 and trehalose.

Solvent

Water for injections, sterilised.

What Optivate looks like and contents of the pack

Optivate, in the form of a white or yellow, crumbly powder, comes in quantities of 250 IU (International Units), 500 IU and 1000 IU in glass vials. These vials are closed with a synthetic rubber stopper under vacuum, held with a tamper-evident cap.

Optivate should only be reconstituted with Sterilised Water for Injections which is supplied with Optivate in plastic ampoules or clear glass bottles.

Marketing Authorisation Holder and Manufacturer

Bio Products Laboratory Limited,

Dagger Lane,

Elstree,

Hertfordshire,

WD6 3BX,

United Kingdom.

Marketing Authorisation Number PL 08801/0055

The leaflet was last approved in

September 2014

For further information or if you have any questions about the use of this product, please contact BPL via the Marketing Department at the address above or through info@bpl.co.uk.

Bio Products Laboratory Limited

Dagger Lane, Elstree, Herts., WD6 3BX, U.K. Tel: +44 (0)20 8957 2200

Bio Products Laboratory

DATE OF LEAFLET PREPARATION September 2014

1627 Optivate PIL UK 3.indd 5 27/08/2014 09:51