Benefix 3000 IU, powder and solvent for solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

BeneFIX 250IU powder and solvent for solution for injection

BeneFIX 500IU powder and solvent for solution for injection

BeneFIX 1000IU powder and solvent for solution for injection

BeneFIX 1500IU powder and solvent for solution for injection

BeneFIX 2000IU powder and solvent for solution for injection

BeneFIX 3000IU powder and solvent for solution for injection

nonacog alfa (recombinant coagulation factor IX)

Read all of this leaflet carefully before you start using 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, pharmacist or nurse.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if it is a side effect not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What BeneFIX is and what it is used for

BeneFIX is a recombinant DNA-derived injectable coagulation factor IX product. The active substance in BeneFIX is nonacog alfa. People born with hemophilia B (Christmas disease) do not have enough factor IX to control bleeding. BeneFIX works by replacing factor IX in patients with hemophilia B, enabling their blood to clot.

BeneFIX is used for the treatment and prevention of bleeding in patients with hemophilia B (congenital factor IX deficiency) across all age groups.

2. What you need to know before using BeneFIX

Do not use BeneFIX

• if you are allergic to nonacog alfa or to any of the other components of this medicine (listed in section 6);
• if you are allergic to hamster proteins.

Warnings and precautions

• Consult your doctor or pharmacist before starting to use BeneFIX.

• Contact your doctor immediately if your bleeding does not stop as expected.

• Allergic reactions may occur. The product may contain traces of hamster proteins (see Do not use BeneFIX). Anaphylactic reactions (severe allergic reactions), which may potentially be life-threatening, have been reported with factor IX products, including BeneFIX. Early signs of allergic reactions include difficulty breathing, shortness of breath, swelling or puffiness, skin rash, itching, generalized hives, chest tightness, wheezing, low blood pressure, blurred vision, and anaphylaxis (a severe allergic reaction that may cause difficulty swallowing and/or breathing, redness or swelling of the face and/or hands).

• If an allergic or anaphylactic reaction occurs, stop the infusion immediately and contact a doctor or seek immediate emergency medical help. In case of severe allergic reactions, alternative therapy should be considered.

• The development of neutralizing antibodies (inhibitors) is an uncommon event in patients who have previously received treatment with factor IX-containing products. Nevertheless, as with all factor IX-containing products, you should be closely monitored for the development of factor IX inhibitors while receiving treatment with BeneFIX.

• Studies have shown an association between the development of a factor IX inhibitor and allergic reactions. Therefore, if you experience allergic reactions such as those described above, you should be tested for the presence of an inhibitor. It should be noted that patients with a factor IX inhibitor may have an increased risk of anaphylaxis during future treatment with BeneFIX.

• Factor IX production in the body is controlled by the factor IX gene. Patients with specific mutations in the factor IX gene, such as a large deletion, may be more likely to develop a factor IX inhibitor and/or experience allergic reactions. Therefore, if you are known to have such a mutation, your doctor may monitor you more closely for signs of an allergic reaction, especially when starting BeneFIX for the first time.

• Due to the risk of allergic reactions with factor IX, initial administrations of BeneFIX should be performed under medical supervision, where appropriate medical care for allergic reactions can be provided.

• Even in the absence of a factor IX inhibitor, higher doses of BeneFIX may be required than those needed for other plasma-derived factor IX products you may have previously received. Therefore, close monitoring of plasma factor IX activity (which measures your blood's ability to form clots) should be performed to appropriately adjust the dose. If bleeding is not controlled with the recommended dose, contact your doctor.

• If you have liver or heart disease or have recently undergone surgery, you may have an increased risk of blood clotting complications.

• Kidney impairment (nephrotic syndrome) has been reported after administration of high doses of plasma-derived factor IX in patients with hemophilia B who have factor IX inhibitors and a history of allergic reactions.

• Sufficient data from clinical trials in previously untreated patients (patients who have never received a factor IX infusion) with BeneFIX are not available.

• It is recommended that each time you use BeneFIX, you record the product name and batch number. You may use one of the peel-off labels on the vial to document the batch number in your diary or to report any adverse reactions.

Other medicines and BeneFIX

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, you should only receive BeneFIX upon specific instruction from your doctor. It is unknown whether BeneFIX can cause harm to the fetus when administered to pregnant women. If you are breastfeeding or become pregnant, your doctor may advise you to discontinue treatment with BeneFIX.

Consult your doctor or pharmacist before using this medicine.

Driving and using machines

BeneFIX has no influence on the ability to drive or operate machinery.

BeneFIX contains sodium

After reconstitution, BeneFIX contains 0.2 mmol of sodium (4.6 mg) per vial; this is essentially “sodium-free”. However, depending on your body weight and dose of BeneFIX, you may receive multiple vials. This should be taken into account if you are on a low-salt diet.

3. How to use BeneFIX

Follow exactly the administration instructions for this medicine given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

Your doctor will decide the dose of BeneFIX you will receive. This dose and its duration will depend on your individual requirements for factor IX replacement therapy and the rate at which your body uses factor IX, which will be monitored regularly. You may notice a difference in the dose you receive if you switch from a plasma-derived factor IX product to BeneFIX.

Your doctor may adjust the dose of BeneFIX you receive during treatment.

Reconstitution and administration

The instructions provided below are a guide for the reconstitution and administration of BeneFIX. Patients must follow the venipuncture instructions specifically indicated by their doctor.

BeneFIX is administered by intravenous (IV) infusion after reconstitution of the lyophilized powder with the solvent provided in the pre-filled syringe (sodium chloride solution).

Always wash your hands before performing the following procedures. During the reconstitution procedure, an aseptic technique (meaning clean and germ-free) must be followed.

Reconstitution:

BeneFIX is administered by intravenous (IV) infusion after reconstitution with sterile solvent for injection.

1. Allow the vial of lyophilized BeneFIX and the pre-filled solvent syringe to reach room temperature.

2. Remove the closure cap from the BeneFIX vial so that the center of the rubber stopper is visible.

1. Clean the top of the vial with the alcohol swab provided or use another antiseptic solution and wait for it to dry. After cleaning, do not touch the rubber stopper with your hands and avoid contact with any surface.

2. Remove the protective cap from the transparent plastic packaging of the adapter. Do not remove the adapter from its packaging.

3. Place the vial on a flat surface. While holding the adapter in its packaging, place it onto the vial. Press firmly until the adapter snaps securely onto the top of the vial, with the tip of the adapter piercing the vial stopper.

1. Remove the adapter packaging and discard it.

1. Attach the plunger rod to the solvent syringe by pushing and firmly turning it.

2. Break the tamper-resistant plastic cap by bending the cap up and down until the perforation breaks. Do not touch the inside of the cap or the tip of the syringe. The cap may need to be replaced (if reconstituted BeneFIX is not administered immediately), so discard it by placing it on top.

1. Place the vial on a flat surface. Connect the solvent syringe to the vial adapter by inserting the syringe tip into the adapter opening, pushing and turning the syringe firmly clockwise until it is securely attached.

1. Slowly depress the plunger to inject all the solvent into the BeneFIX vial.

1. With the syringe still attached to the adapter, gently rotate the vial until the powder is completely dissolved.

1. The final solution should be inspected visually for particulate matter before administration. The solution should appear clear and colorless.

Note: If more than one vial of BeneFIX is used for infusion, each vial must be reconstituted according to the above instructions. The solvent syringe should be discarded, leaving the vial adapter in place, and then a large Luer Lock-type syringe (a device that connects the syringe to the vial) should be used to withdraw the reconstituted contents from each individual vial.

1. Rotate the vial, ensuring the syringe plunger has fully depressed. Slowly aspirate all the solution into the syringe.

1. Disconnect the syringe from the adapter by pushing and slowly turning the syringe clockwise. Discard the vial with the attached adapter.

Note: If the solution is not to be used immediately, the cap should be carefully replaced. Do not touch the syringe tip or the inside of the cap.

BeneFIX must be administered immediately after reconstitution, or within 3 hours thereafter. The reconstituted solution may be stored at room temperature prior to administration.

Administration (Intravenous injection):

BeneFIX should be administered using the pre-filled solvent syringe provided or using a sterile disposable plastic Luer Lock-type syringe. In addition, the solution must be withdrawn from the vial using the vial adapter.

BeneFIX should be injected intravenously over several minutes. Your doctor may adjust the recommended infusion rate to make it more comfortable for you.

Cases of red blood cell agglutination in the tubing or syringe during administration of BeneFIX have been reported. No adverse reactions have been reported in relation to this observation. To minimize the possibility of agglutination, it is important to limit the amount of blood entering the tubing. Blood must not enter the syringe. If red blood cell agglutination is observed in the tubing or syringe, discard all materials (tubing, syringe, and BeneFIX solution) and restart administration with a new kit.

Since the use of BeneFIX in continuous infusion (drip) has not been evaluated, BeneFIX must not be mixed with infusion solutions or administered by drip.

Discard unused solution, empty vials, and used needles and syringes in an appropriate container for sharps disposal if not handled properly.

If you use more BeneFIX than you should

If you inject more BeneFIX than prescribed by your doctor, contact your doctor immediately.

If you stop using BeneFIX

Do not stop treatment with BeneFIX without consulting your doctor.

If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Hypersensitivity/allergic reactions

Allergic-type hypersensitivity reactions may occur with BeneFIX. Such reactions may include swelling of the face or throat, stinging and itching at the infusion site, chills, flushing (reddening of the skin), pruritus, headache, urticaria, decreased blood pressure, lethargy, nausea, restlessness, increased heart rate, chest tightness, tingling, vomiting, wheezing (noises when breathing). In some cases, these reactions have progressed to severe anaphylaxis. Allergic reactions may occur together with the development of factor IX inhibitors (see also “Warnings and precautions”).

These reactions may potentially be life-threatening. If anaphylactic/allergic reactions occur, stop the infusion immediately and contact a doctor or seek immediate emergency medical help. The treatment required will depend on the nature and severity of the adverse effects (see also “Warnings and precautions”).

Development of inhibitors

Patients with haemophilia B may develop neutralizing antibodies (inhibitors) to factor IX. If this occurs, a sign may be an increase in the amount of BeneFIX normally required to treat a bleed, and/or continued bleeding after treatment. In such cases, it is recommended to contact a specialized haemophilia centre. Your doctor may monitor you for the development of inhibitors (see “Warnings and precautions”).

Renal impairment has been reported after administration of high doses of plasma-derived factor IX for immune tolerance induction in patients with haemophilia B who have factor IX inhibitors and a history of allergic reactions (see also “Warnings and precautions”).

Thrombotic events

BeneFIX may increase the risk of thrombosis (abnormal blood clots) in your body if you have risk factors for developing blood clots, including a permanent venous catheter. Serious cases of blood clots, including life-threatening clots in critically ill infants, have been reported while receiving BeneFIX via continuous infusion through a central venous catheter. Cases of peripheral thrombophlebitis (vein pain and redness) and deep vein thrombosis (blood clots in the limbs) have also been reported; in most of these cases, BeneFIX had been administered by continuous infusion, which is a non-approved method of administration.

Very common adverse effects (may affect more than 1 in 10 people)

• Headache
• Cough
• Fever

Common adverse effects (may affect up to 1 in 10 people)

• Hypersensitivity or allergic reactions
• Dizziness, altered sense of taste
• Phlebitis (vein pain and redness), flushing (skin reddening)
• Vomiting, nausea
• Skin rash, urticaria
• Chest discomfort (including chest pain)
• Reaction at the infusion site (including itching and redness at the site), pain and discomfort at the infusion site

Uncommon adverse effects (may affect up to 1 in 100 people)

• Development of neutralizing antibodies (inhibitors)
• Cellulitis at the infusion site (skin pain and redness)
• Somnolence, tremors
• Visual disturbances (including blurred vision, appearance of spots or lights)
• Increased heart rate, decreased blood pressure
• Renal infarction (interruption of blood supply to the kidney)

Adverse effects with unknown frequency (cannot be estimated from available data)

• Anaphylactic reaction
• Thrombotic events (abnormal blood clots)
• Lack of response to treatment (bleeding episodes cannot be stopped or prevented)

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of BeneFIX

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the carton and on the label of the vial. The expiry date refers to the last day of the month indicated.

BeneFIX must be stored below 30°C and used before the expiry date shown on the label.

Do not freeze the product, as this may damage the pre-filled syringe.

The reconstituted product should be used immediately or within 3 hours.

Do not use this medicine if the solution is not clear and colourless.

For reconstitution, only use the pre-filled syringe provided in the pack. For administration, other sterile disposable syringes may be used.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the container and other information

Composition of BeneFIX

• The active substance is nonacog alfa (recombinant coagulation factor IX). Each vial of BeneFIX contains nominally 250, 500, 1000, 1500, 2000, or 3000 IU of nonacog alfa.
• The other components are sucrose, glycine, L-histidine, polysorbate 80. A solvent for reconstitution is included (0.234% sodium chloride solution).
• After reconstitution with the included solvent (0.234% sodium chloride solution), each vial contains 50, 100, 200, 300, 400, or 600 IU, respectively (see Table 1), of nonacog alfa per 1 ml of prepared injection solution.

Table 1. Concentration of BeneFIX per ml of prepared solution

Appearance of the product and contents of the pack

BeneFIX is supplied as a powder for injection in a glass vial and a solvent supplied in a pre-filled syringe.

The pack contains:

• one vial with BeneFIX 250, 500, 1000, 1500, 2000 or 3000 IU powder
• one pre-filled syringe with solvent, 5 ml of 0.234% sodium chloride solution for reconstitution
• one sterile adapter for reconstitution
• one sterile infusion system
• two alcohol swabs
• one adhesive dressing
• one gauze pad

Marketing Authorization Holder

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Brussels

Belgium

Manufacturer responsible for batch release

Wyeth Farma S.A

Autovía del Norte.A-1, Km. 23. Desvío Algete, Km. 1, 28700 San Sebastián de los Reyes, Madrid

Spain

Further information on this medicinal product is available upon request by contacting the local representative of the Marketing Authorization Holder.

Date of the most recent review of this leaflet: 03/2025.

Detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa.eu. There are also links to other websites about rare diseases and orphan medicinal products.