Product Information for the User

BeneFIX 250UI Powder and Diluent for Injectable Solution

BeneFIX 500UI Powder and Diluent for Injectable Solution

BeneFIX 1000UI Powder and Diluent for Injectable Solution

BeneFIX 1500UI Powder and Diluent for Injectable Solution

BeneFIX 2000UI Powder and Diluent for Injectable Solution

BeneFIX 3000UI Powder and Diluent for Injectable Solution

nonacog alfa (recombinant factor IX)

Read this entire product information carefully before starting to use this medication, as it contains important information for you.

• Keep this product information, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you, and you should not give it to others who may have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this product information. See section 4.

1.What is BeneFIX and how is it used

2.What you need to know before starting to use BeneFIX

3.How to use BeneFIX

4.Possible adverse effects

5.Storage of BeneFIX

6.Contents of the package and additional information

BeneFIX is an injectable factor IX coagulation product obtained by recombinant DNA technology. The active substance of BeneFIX is nonacog alfa. Individuals born with hemophilia B (Christmas disease) do not have enough factor IX to control bleeding. BeneFIX acts by replenishing factor IX in patients with hemophilia B to allow their blood to clot.

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

Do not use BeneFIX

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

Warnings and precautions

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

• Consult 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). Severe allergic reactions (anaphylaxis) have been reported with factor IX products, including BeneFIX, which can potentially be life-threatening. Initial signs of allergic reactions include difficulty breathing, wheezing, swelling, hives, itching, generalized urticaria, chest tightness, shortness of breath, low blood pressure, blurred vision, and anaphylaxis (a severe allergic reaction that can cause difficulty swallowing and/or breathing, facial or hand swelling).

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

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

• Studies have shown a relationship between the development of a factor IX inhibitor and allergic reactions. Therefore, if you experience allergic reactions as described above, you should be examined to determine the presence of an inhibitor. It should be noted that patients with a factor IX inhibitor may have an increased risk of anaphylaxis in future treatment with BeneFIX.

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

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

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

• If you have liver or heart disease or have recently undergone surgery, there is a higher risk of blood clotting complications.

• A renal impairment (nephrotic syndrome) has been reported after high-dose administration of factor IX derived from plasma in patients with hemophilia B and inhibitors of factor IX and a history of allergic reactions.

• No sufficient data are available from clinical trials of untreated patients (patients who have never received a factor IX infusion) with BeneFIX.

• It is recommended that each time you use BeneFIX, record the name and batch number of the product. You can use one of the removable labels found in the vial to record the batch number in your diary or to report any adverse reactions.

Other medications and BeneFIX

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, you should only receive BeneFIX on the specific advice of 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 medication.

Driving and operating machinery

The influence of BeneFIX on the ability to drive and operate machinery is negligible.

BeneFIX contains sodium

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

Follow exactly the administration instructions of this medication as indicated 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 needs for factor IX replacement therapy and the speed at which your body uses factor IX, which will be checked 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 modify the dose of BeneFIX you receive throughout treatment.

Reconstitution and Administration

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

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

Wash your hands before performing the following procedures. During the reconstitution procedure, follow aseptic technique (meaning clean and free of germs).

Reconstitution:

BeneFIX will be administered via intravenous infusion (IV) after reconstitution with sterile diluent for injection.

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

1. Remove the closure cap from the vial of BeneFIX so that the central rubber stopper is visible.

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

1. Remove the protective cover from the transparent plastic container of the adapter. Do not remove the adapter from the container.

1. Place the vial on a flat surface. While holding the adapter in its container, place it on top of the vial. Press it firmly until the adapter fits onto the top of the vial, with the tip of the adapter penetrating the rubber stopper of the vial.

1. Remove the container from the adapter and discard it.

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

1. Break the tamper-evident plastic cover by bending the cap upwards and downwards 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 BeneFIX reconstituted is not administered immediately), so discard it by placing it on top.

1. Place the vial on a flat surface. Connect the syringe of diluent to the adapter of the vial by inserting the tip of the syringe into the opening of the adapter while pushing and turning it firmly in a clockwise direction until it fits perfectly.

1. Slowly lower the plunger to inject all the diluent into the vial of BeneFIX.

1. With the syringe still connected to the adapter, gently turn the vial until the powder dissolves.

1. The final solution must be visually inspected for fine particles before administration. The solution must appear transparent and colorless.

Nota: If you use more than one vial of BeneFIX for infusion, each vial must be reconstituted according to the instructions above. The diluent syringe must be discarded, leaving the adapter on the vial and then a large Luer Lock syringe (a device that connects the syringe to the vial) will be used to withdraw the reconstituted contents from each individual vial.

1. Gently turn the vial to ensure the plunger of the syringe has descended completely. Aspirate the solution slowly into the syringe.

1. Release the syringe from the adapter by pushing and turning it slowly in a clockwise direction. Discard the vial attached to the adapter.

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

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

Administration (Intravenous Injection):

BeneFIX must be administered via the pre-filled syringe of diluent provided or via a sterile disposable plastic syringe type Luer Lock. Additionally, the solution must be withdrawn from the vial using the vial adapter.

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

Cases of hematocrit agglutination in the tubing or syringe have been reported during BeneFIX administration. No adverse reactions have been reported in relation to this observation. To minimize the risk of agglutination, it is essential to limit the amount of blood entering the tubing. Blood should not enter the syringe. If hematocrit agglutination is observed in the tubing or syringe, discard all this material (tubing, syringe, and BeneFIX solution) and resume administration with a new container.

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

Discard unused solution, empty vials, and used needles and syringes in an appropriate container for disposing of hazardous waste that may cause injury if not handled properly.

If you use more BeneFIX than you should

If you inject a higher amount of BeneFIX than recommended by your doctor, contact them immediately.

If you interrupt BeneFIX treatment

Do not stop BeneFIX treatment without consulting your doctor.

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

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

Allergic reactions/hypersensitivity

Allergic reactions of a hypersensitivity type may occur with BeneFIX. Such reactions may include swelling of the face or throat, itching and prickling at the site ofinfusion, chills, redness of the skin, pruritus, headache, urticarial rash, decreased blood pressure, drowsiness, nausea, restlessness, increased heart rate, chest tightness, paresthesia, vomiting, wheezing (breathing sounds). In some cases, these reactions have progressed to become severe anaphylaxis. Allergic reactions may occur along 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 required treatment will depend on the nature and severity of the side effects (see also “Warnings and precautions”).

Development of inhibitors

Patients with hemophilia B may develop neutralizing antibodies (inhibitors) to factor IX. If this occurs, a sign may be an increase in the amount of BeneFIX that normally requires treatment for a hemorrhage, and/or that the hemorrhage continues after treatment. In these cases, it is recommended to contact a specialized hemophilia center. Your doctor may monitor you to control the development of inhibitors (see “Warnings and precautions”).

A renal alteration has been reported after administration of high doses of plasma-derived factor IX for immunotolerance induction in patients with hemophilia B with 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 the development of blood clots, including a permanent central venous catheter. Severe cases of blood clots, including life-threatening blood clots in critically ill babies, have been reported while receiving BeneFIX through continuous infusion through a central venous catheter. Also, cases of peripheral thrombophlebitis (pain and redness of the veins) and deep vein thrombosis (blood clots in the extremities) have been reported; in most of these cases, BeneFIX was administered through continuous infusion, which is an unapproved method of administration.

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

• Headache
• Cough
• Fever

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

• Allergic reactions or hypersensitivity
• Dizziness, altered sense of taste
• Phlebitis (pain and redness of the veins), redness of the skin
• Vomiting, nausea
• Skin rash, urticarial rash
• Chest discomfort (including chest pain)
• Reaction at the site ofinfusion(including itching and redness at the site ofinfusion), pain and discomfort at the site ofinfusion

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

• Appearance of neutralizing antibodies (inhibitors)
• Celulitis at the site ofinfusion(pain and redness of the skin)
• Drowsiness, tremors
• Visual disturbances (including blurred vision, appearance of spots or lights)
• Increased heart rate, decreased blood pressure
• Renal infarction (interrupted blood supply to the kidney)

Side effects of 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 side effects

If you experience any type of side effect, consultyour doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in thisleaflet. You can also report them directly through the national reporting system included in Appendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the packaging and on the vial label. The expiration date is the last day of the month indicated.

BeneFIX, must be stored below 30°C and must be used before the expiration date that appears on the label.

Do not freeze the product to avoid damaging the preloaded syringe.

The reconstituted product must be used immediately or within a 3-hour period.

Do not use this medication if you observe that the solution is not transparent or colorless.

For reconstitution, only the preloaded syringe included in the packaging should be used. For administration, other sterile disposable syringes may be employed.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. In this way, you will help protect the environment.

Composition of BeneFIX

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

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-loaded syringe.

The pack contains:

• a vial with BeneFIX 250, 500, 1000, 1500, 2000 or 3000 UI powder
• a pre-loaded syringe with solvent, 5 ml of sodium chloride solution 0.234% for reconstitution
• a sterile reconstitution adapter
• a sterile infusion set
• two alcohol swabs
• a adhesive plaster
• a gauze pad

Marketing authorisation holder

Pfizer Europe MA EEIG

Boulevard de la Plaine 17

1050 Bruxelles

Belgium

Responsible for manufacturing

Wyeth Farma S.A

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

Spain

For further information about this medicinal product, please consult the representative of the marketing authorisation holder in your country.

Last update of this leaflet: 03/2025.

For further information about this medicinal product, please consult the representative of the marketing authorisation holder in your country.

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