Limitations of Use:

IDELVION is not indicated for immune tolerance induction in patients with Hemophilia B.

2.1 Dosage

• Each vial of IDELVION contains the recombinant Factor IX potency in international units (IU) that is stated on the carton and vial label.
• Dosage and duration of treatment with IDELVION depends on the severity of Factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition, age and recovery of Factor IX.
• The calculation of the required dose of IDELVION is based on the empirical finding that one IU of IDELVION per kg body weight is expected to increase the circulating level of Factor IX by 1.3 IU/dL in patients ≥12 years of age and by 1 IU/dL in patients <12 years of age. The required dose of IDELVION for treatment of bleeding episodes is determined using the following formula:

  Required Units (IU) = Body Weight (kg) × Desired Factor IX rise (% of normal or IU/dL) × (reciprocal of recovery (IU/dL per IU/kg))

  OR

  Increase in Factor IX IU/dL (or % of normal) = Dose (IU) × Recovery (IU/dL per IU/kg)/body weight (kg)

• Adjust the dose based on the individual patient's clinical condition and response.

2.2 Preparation and Reconstitution

The procedures below are provided as general guidelines for the preparation and reconstitution of IDELVION.

• Always work on a clean surface and wash your hands before performing the following procedures.
• Use aseptic technique during the reconstitution procedure.
• Reconstitute IDELVION using the diluent (Sterile Water for Injection) and transfer device (Mix2Vial) provided in the kit.
• To administer, you will also need a syringe and suitable needle (not provided).
• Ensure the vials of IDELVION and the Sterile Water for Injection are at room temperature before mixing.
• The reconstitution is performed as described in Table 3.

Table 3: IDELVION Reconstitution Instructions

1. Place the IDELVION vial, diluent vial, and Mix2Vial ® transfer set on a flat surface.
2. Remove flip caps from the IDELVION and Sterile Water for Injection (diluent) vials.
3. Wipe the stoppers with the sterile alcohol swab provided and allow to dry prior to opening the Mix2Vial transfer set package.
4. Open the Mix2Vial transfer set package by peeling away the lid (Fig. 1). Do not remove the device from the package.	Fig. 1
5. Place the diluent vial on a flat surface and hold the vial tightly. Grip the Mix2Vial transfer set together with the clear package and push the plastic spike at the blue end of the Mix2Vial transfer set firmly through the center of the stopper of the diluent vial (Fig. 2).	Fig. 2
6. Carefully remove the clear package from the Mix2Vial transfer set. Do not remove the Mix2Vial transfer set or touch the exposed end of the device (Fig. 3).	Fig. 3
7. With the IDELVION vial placed firmly on a flat surface, invert the diluent vial with the Mix2Vial transfer set attached and push the plastic spike of the transparent adapter firmly through the center of the stopper of the IDELVION vial (Fig. 4). The diluent will automatically transfer into the IDELVION vial.	Fig. 4
8. With the diluent and IDELVION vial still attached to the Mix2Vial transfer set, gently swirl the IDELVION vial to ensure that the powder is fully dissolved (Fig. 5). Do not shake the vial. The reconstituted solution should be a clear or yellow to colorless solution. Do not use if particulate matter or discoloration is observed.	Fig. 5
9. With one hand, grasp the IDELVION side of the Mix2Vial transfer set and with the other hand grasp the blue diluent-side of the Mix2Vial transfer set, and unscrew the set into two pieces (Fig. 6).	Fig. 6
10. Draw air into an empty, sterile syringe. While the IDELVION vial is upright, screw the syringe to the Mix2Vial transfer set. Inject air into the IDELVION vial.
11. While keeping the syringe plunger pressed, invert the system upside down and draw the concentrate into the syringe by pulling the plunger back slowly (Fig. 7).	Fig. 7
12. Disconnect the filled syringe by unscrewing it from the Mix2Vial transfer set (Fig. 8).	Fig. 8
13. Use immediately or within 4 hours of reconstitution. Store reconstituted solution at room temperature. Do not refrigerate.
14. If the dose requires more than one vial, use a separate, unused Mix2Vial transfer set and Sterile Water for Injection (diluent) vial for each product vial. Repeat steps 10-12 to pool the contents of the vials into one syringe.

2.3 Administration

For intravenous injection only.

• Do not mix or administer IDELVION in the same tubing or container with other medicinal products.
• Visually inspect the final solution for particulate matter and discoloration prior to administration, and whenever solution and container permit. Do not use if particulate matter or discoloration is observed.
• Attach the syringe containing the reconstituted IDELVION solution to a sterile infusion set and administer by intravenous injection. Adapt the infusion rate to the comfort level of each patient, not exceeding 10 mL per minute.
• Administer IDELVION at room temperature and within 4 hours of reconstitution. Discard any unused product.

5.1 Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, are possible. Early signs of hypersensitivity reactions, which can progress to anaphylaxis include angioedema, chest tightness, hypotension, generalized urticaria, wheezing, and dyspnea. If hypersensitivity symptoms occur, immediately discontinue administration and initiate appropriate treatment.

IDELVION contains trace amounts of Chinese hamster ovary (CHO) proteins. Patients treated with this product may develop hypersensitivity to these non-human mammalian proteins.

5.2 Neutralizing Antibodies

The formation of neutralizing antibodies (inhibitors) to Factor IX may occur. Monitor all patients treated with IDELVION for the development of neutralizing antibodies (inhibitors) by appropriate clinical observations or laboratory tests. Perform an assay that measures Factor IX inhibitor concentration if expected plasma Factor IX activity levels are not attained, or if the bleeding is not controlled with an appropriate dose.

Patients with Factor IX inhibitors are at an increased risk of severe hypersensitivity reactions or anaphylaxis if re-exposed to Factor IX. eva luate patients experiencing allergic reactions for the presence of an inhibitor and closely monitor patients with inhibitors for signs and symptoms of acute hypersensitivity reactions, particularly during early phases of exposure to the product [see Warnings and Precautions (5.1)].

5.3 Thromboembolic Complications

Thromboembolism (e.g., pulmonary embolism, venous thrombosis, and arterial thrombosis) may occur when using Factor IX-containing products. Because of the potential risk for thromboembolism with the use of Factor IX products, monitor for early signs of thromboembolism and consumptive coagulopathy when administering IDELVION to patients with liver disease, fibrinolysis, perioperative status, or risk factors for thromboembolic events or disseminated intravascular coagulation.

5.4 Nephrotic Syndrome

Nephrotic syndrome has been reported following attempted immune tolerance induction in hemophilia B patients with Factor IX inhibitors and a history of allergic reactions. The safety and efficacy of using IDELVION for immune tolerance induction have not been established.

5.5 Monitoring Laboratory Tests

• Monitor Factor IX plasma levels by a one-stage clotting assay to confirm that adequate Factor IX levels have been achieved and maintained [see Dosage and Administration (2.1)]. Factor IX activity assay results may vary with the type of activated partial thromboplastin time (aPTT) reagent used in the assay system.1 For example, kaolin-based aPTT reagents along with other reagents designed to exhibit low responsiveness to lupus anticoagulant2 have been shown to result in approximately 50% lower than expected recovery based on labeled potency.
• Consistent with similar findings for other recombinant Factor IX products, overestimation of Factor IX activity in spiked samples of IDELVION (mean overestimation 32%) occurred at low Factor IX levels with commonly used aPTT reagents.3
• Monitor patients for the development of inhibitors if expected Factor IX activity plasma levels are not attained, or if bleeding is not controlled with the recommended dose of IDELVION. Assays used to determine if a Factor IX inhibitor is present should be titered in Bethesda Units (BUs).