Drug Detail:Rixubis (Coagulation factor ix [ koe-ag-yoo-lay-shun-fak-tor-nine ])
Generic Name: COAGULATION FACTOR IX RECOMBINANT HUMAN 250[iU] in 5mL;
Dosage Form: injection
Drug Class: Miscellaneous coagulation modifiers
For intravenous use after reconstitution only.
- Each vial of RIXUBIS has the recombinant Factor IX (rFIX) potency in international units stated on the vial.
- Initiate treatment under the supervision of a physician experienced in the treatment of hemophilia.
- Dosage and duration of treatment with RIXUBIS depend on the severity of factor IX deficiency, the location and extent of bleeding, the patient's clinical condition, age, and pharmacokinetic parameters of factor IX, such as incremental recovery and half-life.
- Dosing of RIXUBIS may differ from that of plasma-derived factor IX products [see Clinical Pharmacology (12)]. Subjects at the low end of the observed factor IX recovery range may require dose adjustment of RIXUBIS.
- Monitor patients using a factor IX activity assay to ensure that the desired factor IX activity plasma level has been attained. If necessary, adjust the dose and the frequency of repeated infusions as appropriate.
- Evaluate the patient for the development of factor IX inhibitors if the expected factor IX activity plasma levels are not attained or if bleeding is not controlled with an appropriate dose [see Warnings and Precautions (5.2)].
Dosing Guidelines
Calculating Initial Dose
The initial dose of RIXUBIS is calculated based on the empirical finding that one international unit of RIXUBIS per kg body weight is expected to increase the circulating level of factor IX by 0.7 international units/dL of plasma (0.7% of normal) for patients <12 years of age and by 0.9 international units/dL of plasma (0.9% of normal) in patients ≥12 years of age.
A guide for calculating the initial dose of RIXUBIS for treatment of bleeding episodes is as follows:
| Initial Dose = body weight (kg) × desired factor IX increase (% of normal or IU/dL) × reciprocal of observed recovery (IU/kg per IU/dL) |
Incremental Recovery in Previously Treated Patients (PTPs)
Base the calculation of the dose on the patient's individual incremental recovery using serial factor IX activity assays, due to the wide range of inter-individual differences in incremental recovery. Titrate the dose based on the patient's clinical response and individual pharmacokinetics, in particular incremental recovery and half-life.
Patients <12 Years of Age
On average, a 22% lower recovery has been observed in pediatric patients (<12 years, n=23). For an incremental recovery of 0.7 international units/dL of plasma (0.7% of normal), the dose is calculated as follows:
| Dose (international units) = body weight (kg) × desired factor IX increase (% of normal or IU/dL) × 1.4 dL/kg |
Example (assuming patient's baseline factor IX level is <1% of normal)
- A dose of 1500 international units of RIXUBIS, administered to a 20 kg patient should be expected to result in a peak post-infusion factor IX increase of 1500 international units × {[0.7 IU/dL]/[IU/kg]}/[20 kg] = 53.6 international units/dL (53.6% of normal).
Patients ≥12 Years of Age
For an incremental recovery of 0.9 international units/dL of plasma (0.9% of normal), the dose is calculated as follows:
| Dose (international units) = body weight (kg) × desired factor IX increase (% of normal or IU/dL) × 1.1 dL/kg |
Examples (assuming patient's baseline factor IX level is <1% of normal):
- A dose of 4550 international units of RIXUBIS, administered to a 70 kg patient, should be expected to result in a peak post-infusion factor IX increase of 4550 international units × {[0.9 IU/dL]/[IU/kg]}/[70 kg] = 58.5 international units/dL (58.5 % of normal).
- A peak level of 70% is required in a 60 kg patient. The appropriate dose would be 60 kg × 70 international units/dL/{[0.9 IU/dL]/[IU/kg]} = 4667 international units.
On-demand Treatment and Control of Bleeding Episodes and Perioperative Management of Bleeding
A guide for dosing RIXUBIS in the on-demand treatment and control of bleeding episodes and perioperative management of bleeding is provided in Table 1 and Table 2, respectively. Ensure the factor IX activity level is achieved and maintained in the corresponding period.
| Type of Bleeding Episodes | Circulating Factor IX Level Required (% or IU/dL) | Dosing Interval (hours) | Duration of Therapy (days) |
|---|---|---|---|
| Adapted from Roberts and Eberst1 | |||
| Minor Uncomplicated hemarthrosis, superficial muscular or soft tissue |
20-30 | 12-24 | At least 1 day, until healing is achieved |
| Moderate Intramuscular or soft tissue with dissection, mucous membranes, hematuria |
25-50 | 12-24 | 2-7 days, until bleeding stops, and healing is achieved |
| Major Pharyngeal, retropharyngeal, retroperitoneal, CNS |
50-100 | 12-24 | 7-10 days, until bleeding stops, and healing is achieved |
| Type of Surgery | Circulating Factor IX Level Required (% or IU/dL) | Dosing Interval (hours) | Duration of Therapy (days) |
|---|---|---|---|
| Minor e.g., tooth extraction |
30-60 | 24 | At least 1 day, until healing is achieved |
| Major e.g., intracranial, intraabdominal, intrathoracic, joint replacement |
80-100 | 8-24 | 7-10 days, until bleeding stops and healing is achieved |
Routine Prophylaxis
The dose for previously treated patients (PTPs) is 60 to 80 international units per kg twice weekly for patients <12 years of age and is 40 to 60 international units per kg twice weekly for patients ≥12 years of age. Adjust the dose based on the individual patient's age, bleeding pattern, and physical activity.
Preparation and Reconstitution
The procedures below are provided as general guidelines for the preparation and reconstitution of RIXUBIS. Always work on a clean surface and wash hands before performing the following procedures:
- Use aseptic technique during reconstitution procedure.
- Allow the RIXUBIS vial (dry factor concentrate) and Sterile Water for Injection, USP vial (diluent) to reach room temperature.
- Remove caps from the factor concentrate and diluent vials.
- Cleanse stoppers with germicidal solution and allow the stopper to dry prior to use. Place the vials on a flat surface.
- Open the BAXJECT II device package by peeling away the lid, without touching the inside (Figure A). Do not remove the device from the package. Note that the BAXJECT II device is intended for use with a single vial of RIXUBIS and Sterile Water for Injection, USP only; therefore, reconstituting and withdrawing a second vial into the syringe requires a second BAXJECT II device.
- Turn the package over. Press straight down to fully insert the clear plastic spike through the diluent vial stopper (Figure B).
- Grip the BAXJECT II package at its edge and pull the package off the device (Figure C). Do not remove the blue cap from the BAXJECT II device. Do not touch the exposed white plastic spike.
- Turn the system over so that the diluent vial is on top. Quickly insert the white plastic spike fully into the RIXUBIS vial stopper by pushing straight down (Figure D). The vacuum will draw the diluent into the RIXUBIS vial.
- Swirl gently until the powder is completely dissolved. Do not refrigerate after reconstitution. Use within 3 hours of reconstitution.
Administration
For intravenous bolus infusion only.
- The safety and efficacy of RIXUBIS administration by continuous infusion has not been established.
- Inspect parenteral drug products for particulate matter and discoloration prior to administration. The solution should be clear and colorless in appearance. Do not use RIXUBIS if you notice any particulates or turbidity in the solution and notify Takeda Pharmaceuticals.
- Perform product administration and handling of the administration set and needles with caution. Percutaneous puncture with a needle contaminated with blood can transmit infectious viruses including HIV (AIDS) and hepatitis. Obtain immediate medical attention if injury occurs. Place needles in a sharps container after single-use.
- Administer RIXUBIS at room temperature and within 3 hours of reconstitution. Discard any unused product.
- Use a plastic syringe with this product.
- Remove the blue cap from the BAXJECT II device. Connect the syringe to the BAXJECT II device by screwing it clockwise until the syringe is secured (Figure E). Do not over tighten.
- Do not inject air.
- Turn the system upside down (factor concentrate vial now on top). Draw the factor concentrate into the syringe by pulling the plunger back slowly (Figure F).
- Disconnect the syringe by unscrewing it counterclockwise; attach a suitable needle to the syringe and inject intravenously by bolus infusion. If a patient is to receive more than one vial of RIXUBIS, the contents of multiple vials may be drawn into the same syringe.
- Maximum infusion rate of 10 mL/min.
Figure A |
Figure B |
Figure C |
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Figure D |
Figure E |
Figure F |
