BeneFix

BeneFix (coagulation factor IX) is a once-weekly, injectable, treatment for hemophilia B that may be used to control and prevent bleeding in adults and children with hemophilia B.

Hemophilia B is a condition where the blood lacks enough Factor IX for proper clotting. BeneFix works by temporarily replacing this missing factor, allowing the blood to clot effectively and prevent bleeding. BeneFix is NOT used to treat hemophilia A.

BeneFix was FDA-approved on February 11, 1997.

BeneFix may be used in adults and children with hemophilia B (congenital factor IX deficiency or Christmas disease) for:

• On-demand treatment and control of bleeding episodes
• Management of bleeding during surgery
• As a preventive to reduce the frequency of bleeding episodes.

Limitations of Use

BeneFix is not indicated for induction of immune tolerance in patients with hemophilia B.

BeneFix is administered by an intravenous (into a vein) injection, directly into the bloodstream. It is usually administered by a healthcare provider initially, but people can be taught how to self-administer it themselves, or a caregiver can be taught how to administer it to a person with hemophilia B.

• Do not attempt to administer BeneFix yourself unless you have been shown how to do so by a healthcare provider.
• Follow the step-by-step instructions provided in the product information.
• BeneFix needs to be diluted before use. Once diluted, it should be administered immediately or within 3 hours of mixing.
• BeneFix should not be administered by continuous infusion.

The frequency of administration depends on what BeneFix is being used to treat, but it is usually given every 7 days to prevent bleeding episodes.

Do not use BeneFix for a condition for which it is not prescribed or share it with other people, even if they have the same symptoms as you.

Note: If red blood cell clumping is observed in the tubing or syringe, discard all material (tubing, syringe, and BeneFix solution) and continue administration with a new package.

It is a good idea to record the lot number from the BeneFix vial label every time you use BeneFix. You can use the peel-off label on the vial to record the lot number.

Before receiving BeneFix, you should tell your healthcare provider if you:

• have or had any medical problems
• take any medicines, including prescription and non-prescription medicines, such as over-the-counter medicines, supplements, or herbal remedies
• have had an allergic reaction to any Factor IX product before using BeneFix
• have any allergies, including allergies to hamster proteins
• have been told that you have inhibitors to Factor IX (because BeneFix may not work for you)
• are pregnant or planning to become pregnant
• are breastfeeding.

Pregnancy

It is not known if BeneFix can harm your unborn baby. Talk to your healthcare provider about the risks involved with receiving BeneFix if you are pregnant.

Breastfeeding

It is not known if BeneFix passes into your milk and if it can harm your baby. Talk to your healthcare provider about the best way to feed your baby during treatment with BeneFix.

The most common side effects of BeneFix are:

• fever
• cough
• nausea
• injection site reactions (redness, swelling, pain)
• headache
• dizziness
• rash.

Do not receive BeneFix if you:

• have had life-threatening hypersensitivity reactions to BeneFix, other coagulation factor IX products, or any of the inactive ingredients in the vial or diluent
• are allergic to hamster proteins.

BeneFix can cause serious side effects.

Allergic and hypersensitivity reactions have been reported with BeneFix. Patients may develop hypersensitivity to hamster (CHO) protein as BeneFIX contains trace amounts. Call your healthcare provider right away and stop treatment if you get a rash or hives, itching, tightness of the chest or throat, difficulty breathing, light-headedness, dizziness, nausea, or a decrease in blood pressure.

Your body can make antibodies, called inhibitors, against Factor IX, which may stop BeneFix from working properly. Your healthcare provider may need to test your blood for inhibitors from time to time.

BeneFix may increase the risk of forming abnormal blood clots in your body, especially if you have risk factors for developing blood clots, including an indwelling venous catheter through which BeneFix is given by continuous infusion. Call your healthcare provider if you have chest pain, difficulty breathing, leg tenderness, or swelling.

Nephrotic syndrome (a kidney disorder that causes your body to pass too much protein in your urine) has been reported following immune tolerance induction with factor IX products in hemophilia B patients with factor IX inhibitors and a history of allergic reactions to factor IX.

These are not the only side effects possible with BeneFix. To learn more, talk to your healthcare provider or pharmacist. Tell your healthcare provider about any side effect that bothers you or does not go away. You may report side effects to Wyeth Pharmaceuticals LLC at 1-800-934-5556 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

Your healthcare provider will tell you how much BeneFix to administer based on your weight, the severity of your hemophilia B, or where you are bleeding. BeneFix may be used:

• To control and prevent bleeding episodes
• During surgery
• To reduce the number of bleeding episodes when used regularly (prophylaxis).

Calculating the initial dose

In adults, on average, 1 international unit (IU) of BeneFIX per kilogram of body weight increased the circulating activity of factor IX as follows:

• Adolescents/Adults (≥12 years): 0.8 ± 0.2 IU/dL (range 0.4 to 1.2 IU/dL)
• Children (<12 years): 0.7 ± 0.3 IU/dL (range 0.2 to 2.1 IU/dL).

Determine the initial estimated dose using the following formula

• Required units = body weight (kg) × desired factor IX increase (IU/dL or % of normal) × reciprocal of observed recovery (IU/kg per IU/dL)

The dosage and duration of treatment with BeneFix depend on the severity of the factor IX deficiency, the location and extent of bleeding, the patient's clinical condition, age, and recovery of factor IX.

• You may need to have blood tests done after administering BeneFix to be sure that the blood level of Factor IX is high enough to clot the blood.

Call your healthcare provider right away if your bleeding does not stop after administering BeneFix.

Dosing for on-demand treatment and control of bleeding episodes and perioperative management

Routine Prophylaxis

• For long-term prophylaxis against bleeding, the recommended regimen is 100 IU/kg once weekly. Children less than 12 years old have a lower recovery, shorter half-life, and higher clearance compared with adolescents and adults. Adjust the dosing regimen (dose or frequency) based on the patient's clinical response.

BeneFix comes in five different dosage strengths which are printed on the vial label:

• 250 IU (yellow)
• 500 IU (blue)
• 1000 IU (green)
• 2000 IU (red)
• 3000 IU (grey).

Always check the actual dosage strength printed on the label to make sure you are using the strength prescribed by your healthcare provider.

If you miss a dose, administer that dose as soon as possible and then resume your regular dosing schedule. Call your healthcare provider for more information.

Call your healthcare provider or call the Poison Help line at 1-800-222-1222.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. BeneFix may affect the way other medicines work. Especially tell your healthcare provider if you take other medications that:

• affect the way your blood clots, such as carfilzomib
• affect other coagulation factors, such as efgartigimod alfa or Rozanolixizumab

Know the medicines you take and the vaccines you receive. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. See the prescribing information for a full list of interactions.

Store the unmixed vial of BeneFix in its original carton to protect it from light. It can be stored in the refrigerator or at room temperature at 36-86°F (2-30°C). Do not freeze.

Do not use it after the expiration date printed on the label.

Once the dry product has been mixed with the diluent (reconstituted) it must be used within 3 hours. Do not refrigerate, keep at room temperature. Do not use BeneFix if the reconstituted solution is not clear and colorless.

Discard any BeneFix left in the vial at the end of your infusion.

Active: recombinant human coagulation Factor IX

Inactive: 0.234% sodium chloride, 8 mM L-histidine, 0.8% sucrose, 208 mM glycine, 0.004% polysorbate 80.

Contains no preservatives.

Available in the following unit strengths: 250, 500, 1000, 2000, or 3000 IU.

BeneFix, when reconstituted, contains polysorbate-80, which is known to increase the rate of di-(2-ethylhexyl) phthalate (DEHP) extraction from polyvinyl chloride (PVC). This should be considered during the preparation and administration of BeneFix, including storage time elapsed in a PVC container following reconstitution. The tubing of the infusion set included in this kit does not contain DEHP.

Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc., makes BeneFix.