Factor IX (Recombinant [Fc Fusion Protein])

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Allergic side effects may rarely happen.
• Blood clots have happened with factor IX. Tell your doctor if you have ever had a blood clot. Talk with your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Call the doctor right away if the normal dose does not work as well.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• A burning, numbness, or tingling feeling that is not normal.
• Upset stomach or throwing up.
• Shortness of breath.
• Dizziness or passing out.
• Restlessness.
• Call your doctor right away if you have signs of a blood clot like chest pain or pressure; coughing up blood; shortness of breath; swelling, warmth, numbness, change of color, or pain in a leg or arm; or trouble speaking or swallowing.

Hypersensitivity (eg, anaphylaxis) to factor IX (recombinant [Fc fusion protein]) or any component of the formulation (ie, sucrose, mannitol, sodium chloride, L-histidine, and polysorbate 20).

Note: Contains only factor IX. Therefore, NOT INDICATED for the treatment of other factors deficiencies (eg, factors II, VII, VIII, and X), hemophilia A patients with inhibitors to factor VIII, reversal of coumarin-induced anticoagulation, and bleeding due to low levels of liver-dependent clotting factors.

Control or prevention of bleeding in patients with factor IX deficiency (hemophilia B or Christmas disease): IV: Dosage is expressed in units of factor IX activity; dosing must be individualized based on severity of factor IX deficiency, extent and location of bleeding, clinical status of patient, and recovery of factor IX. Refer to product information for specific manufacturer recommended dosing. Alternatively, the World Federation of Hemophilia (WFH) has recommended general dosing for factor IX products.

Formula for units required to raise blood level %: Note: If patient has severe hemophilia (ie, baseline factor IX level is or presumed to be <1%), then may just use “desired factor IX level” instead of “desired factor IX level increase”.

Number of factor IX units required = patient weight (in kg) x desired factor IX level increase (as % or units/dL) x reciprocal of observed recovery (as units/kg per units/dL)

Alternative dosing (off-label): Note: The following recommendations may vary from those found within prescribing information or practitioner preference.

Prophylaxis: 15 to 30 units/kg/dose twice weekly (Utrecht protocol; WFH [Srivastava 2013]) or 25 to 40 units/kg/dose twice weekly (Malmö protocol; WFH [Srivastava 2013]) or 40 to 100 units/kg/dose 2 to 3 times weekly (National Hemophilia Foundation, MASAC recommendation 2007); optimum regimen has yet to be defined.

Treatment:

Desired Factor IX Level to Maintain and Duration Based on Site of Hemorrhage/Clinical Situation:

Joint: 40 to 60 units/dL for 1 to 2 days, may be longer if response is inadequate

Superficial muscle (no neurovascular compromise): 40 to 60 units/dL for 2 to 3 days, sometimes longer if response is inadequate

Iliopsoas and deep muscle with neurovascular injury, or substantial blood loss: Initial: 60 to 80 units/dL for 1 to 2 days; Maintenance: 30 to 60 units/dL for 3 to 5 days, sometimes longer as secondary prophylaxis during physiotherapy

CNS/head: Initial: 60 to 80 units/dL for 1 to 7 days; Maintenance: 30 units/dL for 8 to 21 days

Throat and neck: Initial: 60 to 80 units/dL for 1 to 7 days; Maintenance: 30 units/dL for 8 to 14 days

Gastrointestinal: Initial: 60 to 80 units/dL for 7 to 14 days; Maintenance: 30 units/dL (duration not specified)

Renal: 40 units/dL for 3 to 5 days

Deep laceration: 40 units/dL for 5 to 7 days

Surgery (major): Preop: 60 to 80 units/dL; Postop: 40 to 60 units/dL for 1 to 3 days; then 30 to 50 units/dL for 4 to 6 days; then 20 to 40 units/dL for 7 to 14 days

Surgery (minor): Preop: 50 to 80 units/dL; Postop: 30 to 80 units/dL for 1 to 5 days depending on procedure type

Note: Factor IX level may either be expressed as units/dL or as %. Dosing frequency most commonly corresponds to the half-life of factor IX but should be determined based on an assessment of factor IX levels before the next dose.

Routine prophylaxis to prevent bleeding episodes in patients with factor IX deficiency (hemophilia B or Christmas disease): IV: 50 units/kg once weekly or 100 units/kg once every 10 days; adjust dose based on individual response

Refer to adult dosing.

Note: Contains only factor IX. Therefore, NOT INDICATED for the treatment of other factors deficiencies (eg, factors II, VII, VIII, and X), hemophilia A patients with inhibitors to factor VIII, reversal of coumarin-induced anticoagulation, and bleeding due to low levels of liver-dependent clotting factors.

Control or prevention of bleeding in patients with factor IX deficiency (hemophilia B or Christmas disease): IV: Dosage is expressed in units of factor IX activity; dosing must be individualized based on severity of factor IX deficiency, extent and location of bleeding, clinical status of patient, and recovery of factor IX. . Refer to product information for specific manufacturer recommended dosing. Alternatively, the World Federation of Hemophilia (WFH) has recommended general dosing for factor IX products.

Formula for units required to raise blood level %: Note: If patient has severe hemophilia (ie, baseline factor IX level is or presumed to be <1%), then may just use “desired factor IX level” instead of “desired factor IX level increase”.

Infants, Children, and Adolescents: IV: Number of factor IX units required = patient weight (in kg) x desired factor IX level increase (as % or units/dL) x reciprocal of observed recovery (as units/kg per units/dL)

Alternative recommendations (off label): Infants, Children, and Adolescents:

Prophylaxis: Refer to adult dosing.

Treatment: Refer to adult dosing.

Routine prophylaxis to prevent bleeding episodes in patients with factor IX deficiency (hemophilia B or Christmas disease): IV: 50 units/kg once weekly or 100 units/kg once every 10 days; adjust dose based on individual response

Refer to instructions provided by the manufacturer. Diluent and factor IX should come to room temperature (if refrigerated) before combining.

Administer by IV bolus infusion; maximum rate of administration: 10 mL/minute.

Solution should be infused at room temperature. Safety and efficacy of continuous infusion administration have not been determined.

Per the WFH, infuse by slow IV injection at a rate not to exceed 3 mL/minute (adults) or 100 units/minute (young children). With patients who have had allergic reactions during factor IX infusion, administration of hydrocortisone prior to infusion may be necessary (WFH [Srivstava 2013]).

Factor IX levels by the one-stage clotting assay (measure 15 minutes after infusion to verify calculated doses (WFH [Srivastava 2013]), aPTT, BP, HR, signs of hypersensitivity reactions, DIC, and thrombosis; screen for factor IX inhibitors if the patient experiences hypersensitivity reaction or when patient is to undergo surgery, if suboptimal response to treatment occurs, if patient is being intensively treated for >5 days within 4 weeks of the last infusion, or at the following intervals ( WFH [Srivastava 2013]):

Children: Screen for inhibitors every 5 exposure days until 20 exposure days, every 10 exposure days between 21 to 50 exposure days, and at a minimum of twice a year until 150 exposure days is reached.

Adults (with >150 exposure days apart from a 6 to 12 monthly review): Screen for inhibitors when suboptimal response occurs.