Nonafact 100 IU/ml powder and solvent for solution forinjection

Nonafact can be administered to prevent and treat bleeding in patients suffering from haemophilia B (a congenital lack of active factor IX). Factor IX is a normal constituent of human blood. A deficiency of factor IX causes blood coagulation problems, which may lead to bleeding in joints, muscles or internal organs. The administration of Nonafact can compensate for this deficiency.

Do not use Nonafact:

• if you are hypersensitive (allergic) to the active substance, human coagulation factor IX.
• if you are hypersensitive (allergic) to any of the other ingredients or to mouse proteins.

Take special care with Nonafact:

See your doctor immediately, if bleeding does not stop as expected.

After it has been dissolved in the supplied water for injections, the product should be clear. Check this immediately prior to administration. The product must not be administered if any cloudiness, lumps or particulate matter are visible.

In rare cases, Nonafact can give rise to a severe allergic reaction (anaphylactic shock). If, after administration, you develop hypersensitive reactions like hives, itching and rash, chest tightness, wheezing and light headedness contact your physician immediately. If you have previously experienced hypersensitivity in response to the administration of blood or a blood product,Nonafactshould only be administered when absolutely necessary (in life-threatening situations). This must be carried out in hospital or under the careful supervision of a doctor.

Individuals with haemophilia B who receive factor IX preparations, should be monitored for the development of neutralising antibodies against factor IX (inhibitors) (see Possible side effects). Your doctor will check your blood regularly for the presence of these antibodies, especially if you experienced a severe allergic reaction with the previous use of a factor IX product. The occurrence of activity-neutralising antibodies (inhibitors) is a very rare event in previously treated patients receiving factor IX-containing products.

There is a slight risk that higher doses of Nonafact will cause clots to form in blood vessels, resulting in thrombosis. If you suffer from a liver or cardiac disease or if you have recently had surgery, there is an increased risk for coagulation complications. This also applies to newborn babies and patients with an increased risk of thrombosis or ?DIC?, disseminated intravascular coagulation, a disease in which the blood coagulation system is disturbed. Your doctor will consider whether administration of Nonafact imposes a risk for coagulation complications.

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.

Your doctor may recommend that you consider vaccination against hepatitis A and B if you regularly/repeatedly receive human plasma-derived coagulation factor IX

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

There is no experience of the treatment of previously untreated patients with Nonafact.

Use in children

There are insufficient data to recommend the use of Nonafact in children less than 6 years of age.

Using other medicines:

There are no known interactions between Nonafact and other medicinal products.
Please inform your doctor or pharmacist if you are taking or have recently taken any other medicines, even those not prescribed.

Pregnancy and breast-feeding:

Based on the rare occurrence of haemophilia B in women, experience regarding the use of factor IX during pregnancy and breast-feeding is not available. Therefore, factor IX should be used by pregnant or breast-feeding women only if clearly indicated.
Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines:

Nonafact has no known effects on the ability to drive and to use machines.

Information about some of the ingredients of Nonafact:

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ?sodium- free?.

Dosage:

Your doctor will decide how much Nonafact you require. The exact dose will depend on the seriousness of the clinical situation, your body weight and the amount of factor IX in your blood. If you have to undergo surgery or have a tooth extracted, inform your doctor or dentist that you have factor IX deficiency. They will then ensure that factor IX is administered to you, should this prove necessary.

Nonafact is given to you by your doctor or nurse. Nonafact may be self administered if it is an approved practice in your country and when you have been trained sufficiently. Always use Nonafact exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

It is important that the concentration of factor IX in your blood is checked regularly. If you are administered 1 IU per kilogram of body weight, the concentration of factor IX in your blood will increase by 1.1 % of normal activity.

The required dosage is determined using the following formula:

Required units = body weight (kg) x desired factor IX rise (%) (IU/dl) x 0.9

Your doctor will determine the dose of Nonafact you need and how frequently you should use it depending on the situation. The following table can be used to guide dosing in bleeding episodes and surgery:

Degree of bleeding Type of surgical procedure Factor IX level Frequency of doses hoursDuration required of therapy days IUdl

Bleeding 20-40 Early signs of bleeding in joints, muscle bleeding or oral bleeding Repeat every 24 hours. At least 1 day, until the bleeding episode as indicated by pain is resolved or healing is achieved. 30-60 More extensive bleeding in joints, muscle bleeding or haematoma Repeat infusion every 24 hours for 3-4 days or more until pain and acute disability are resolved.

Life threatening bleeding 60-100 Repeat infusion every 8 to 24 hours until threat is resolved.

Surgery 30-60 Minor including tooth extraction Every 24 hours, at least 1 day, until healing is achieved.

80-100 Major Repeat infusion every 8-24 hours until adequate wound healing, then therapy for at least another 7 days. pre- and postoperative

During the course of treatment it is advised that the concentrations of factor IX in your blood are checked regularly. Particularly with major surgery, it is important that the concentrations of factor IX in your blood are checked carefully before and after the operation.

For long-term prevention of bleeding in individuals with severe haemophilia B, doses of 20 IU to 40 IU of factor IX per kilogram body weight should be given at intervals of 3 to 4 days. In some cases, especially in younger patients, shorter dosage intervals or higher doses may be necessary.

If you have the impression that the effect of Nonafact is too strong or too weak, talk to your doctor. Individuals with haemophilia B may develop antibodies (inhibitors) against factor IX. As a result, the factor IX product used becomes inactivated (see Possible side effects). It is advised that the treatmentof this serious condition be taken care of in a haemophilia treating centre where an appropriate dose will be determined. The administration of factor IX can repress these inhibitors.

Instructions for use:

Dissolving the powder

The powder should be dissolved in the supplied amount of water for injections. The solution should not be too cold when it is administered. In addition, the powder will dissolve more readily if both vials are first allowed to reach room temperature (15°C ? 25°C).

1. Remove from the refrigerator and allow the two vials to reach room temperature (15°C ? 25°C).

2. Remove the plastic cap from the vials.

3. Disinfect the surface of the stoppers of both vials with a gauze soaked in 70 % alcohol.

4. Remove the protective sheath from one end of a transfer needle and pierce the stopper of the vial containing water for injections. Remove the protective sheath from the other end of the transfer needle. Invert the solvent vial and pierce the stopper of the vial containing the powder.

5. Tilt the product vial when transferring the solvent to allow the solvent to flow down the side of the vial.

6. Remove the empty vial and the transfer needle.

7. Swirl the vial gently to completely dissolve the powder. Do not shake! The powder dissolves within 5 minutes to produce a clear, colourless to light-yellow solution.

Immediately before administration, the solution should be inspected: the solution should be clear and must be free of lumps. Once dissolved, the product should be used immediately (at least within 3 hours).

Nonafact should never be mixed with other medicinal products.

Administration

1. Using a hypodermic needle and syringe, draw the dissolved product out of the vial.

2. Nonafact should be injected into a vein (intravenous administration).

3. Inject the dissolved product very gradually (approx. 2 ml per minute).

Disposal

Any unused product or waste material must be discarded as instructed by your doctor or pharmacist.

Duration of treatment:

Haemophilia B is a chronic disease, therefore lifelong treatment with a factor IX product may be necessary.

If you use more Nonafact than you should:

No symptoms of overdose with human coagulation factor IX have been reported.

As with all medicinal products derived from human blood, the use of Nonafact can cause allergic reactions which may include swelling of the larynx, burning and stinging at the infusion site, chills, flushing, hives, itching and rash, headache, tiredness, nausea, restlessness, fast heart beat, chest tightness, tingling, vomiting, wheezing.
You should discuss the possible side effects with your doctor in order to know how to recognise them and what to do if they occur. Where necessary, mild allergic reactions, such as hives, can be treated with antihistamines (medicinal products which counteract allergies). In the case of a severe allergic reaction (anaphylactic shock), immediately stop the administration of the product and contact your doctor immediately.

There is a very slight risk that Nonafact will cause clots to form in blood vessels, resulting in thrombosis. The use of Nonafact may also produce an increase in body temperature in rare cases.

Your body may develop antibodies (inhibitors) against factor IX, which will inactivate Nonafact. Your doctor will check your blood regularly for the presence of these antibodies. Contact your doctor immediately if you suspect that the product is becoming progressively less effective. This will show itself as an increased tendency to bleed.

If you need therapy for repressing antibodies (inhibitors) this should be taken care of in a haemophilia treating centre. You will be closely monitored for any possible side effect during this treatment.

If you should experience one of these side effects, you are advised to contact your doctor. If you notice any side effects not mentioned in this leaflet, please inform your doctor or pharmacist.

Keep out of the reach and sight of children.

Do not use after the expiry date stated on the label and carton.
Store in a refrigerator (at 2°C ? 8°C ).

Keep the vial in the outer carton in order to protect from light.
From a microbiological point of view the product, once dissolved, should be used immediately, but no longer than 3 hours after reconstitution.

Before administration, check that the solution is clear. The product must not be used if any cloudiness, lumps or particulate matter are visible.

Nonafact 100 IU/ml human coagulation factor IX

What Nonafact contains:

• The active substance is human coagulation factor IX. Each vial contains 500 IU or 1000 IU of human coagulation factor IX.
• The other ingredients are sodium chloride, sucrose, histidine and water for injections.

What Nonafact looks like and contents of the pack:

Nonafact is presented as a powder and a solvent for solution for injection (vial of 5 ml or 10 ml)

Nonafact consists of a carton containing:

• A vial of Nonafact containing 500 IU or 1000 IU of factor IX
• A vial water for injections containing 5 ml or 10 ml

Marketing Authorisation Holder and Manufacturer

Sanquin, Plesmanlaan 125 NL, 1066 CX Amsterdam, the Netherlands

This leaflet was last approved