Bleeding disorders:
Indications for: BENEFIX
On-demand treatment and control of bleeding in hemophilia B. Perioperative management in patients with hemophilia B. Routine prophylaxis to reduce the frequency of bleeding episodes in patients aged ≥16yrs with hemophilia B.
Limitations of Use:
Not for induction of immune tolerance in patients with hemophilia B.
Clinical Trials:
Efficacy of BeneFIX has been evaluated in clinical trials in which a total of 153 patients received BeneFIX either for the on-demand treatment and control of bleeding episodes, perioperative management, and routine prophylaxis in patients with hemophilia B.
On-demand Treatment and Control of Bleeding Episodes
Fifty-six previously treated patients (PTPs) and sixty-three previously untreated patients (PUPs) were treated for bleeding episodes on an on-demand treatment and control of bleeds. The PTPs were followed over a median interval of 24 months (mean 23.4 ± 5.3 months) and for a median of 83.5. The PUPs were followed over a median interval of 37 months (mean 38.1 ± 16.4 months) and for a median of 89 exposure days.
Fifty-five PTPs and fifty-four PUPs received BeneFIX for the treatment of bleeding episodes. Bleeding episodes that were managed successfully included hemarthrosis and bleeding in soft tissue and muscle. In the PTPs, 88% of total infusions administered for on-demand treatment were rated as an “excellent” or “good” response.
A total of 20 PTPs were treated with BeneFIX for secondary prophylaxis (the regular administration of FIX replacement therapy to prevent bleeding in patients who may have already demonstrated clinical evidence of hemophilic arthropathy or joint disease) at some regular interval during the trial with a mean of 2 infusions per week. Thirty-two PUPs were administered BeneFIX for routine (primary and secondary) prophylaxis. Seven PTPs experienced a total of 26 spontaneous bleeding episodes within 48 hours after an infusion. Six spontaneous bleeds within 48 hours after an infusion were reported in 5 PUPs. Prophylaxis therapy was rated as “excellent” or “effective” in 93% of PTPs receiving prophylaxis one to two times per week.
Perioperative Management
Management of hemostasis was evaluated in the surgical setting in both PTPs and PUPs. Thirty-six surgical procedures have been performed in 28 PTPs with 23 major surgical procedures performed (including 6 complicated dental extractions). Thirty surgical procedures have been performed in 23 PUPs. Twenty-eight of these procedures were considered minor. Hemostasis was maintained throughout the surgical period; however, one PTP subject required evacuation of a surgical wound-site hematoma, and another PTP subject who received BeneFIX after a tooth extraction required further surgical intervention due to oozing at the extraction site. There was no clinical evidence of thrombotic complications in any of the subjects. See full labeling for results.
Routine Prophylaxis
In an open-label trial of 25 patients (age range 12-54 years) comparing on-demand treatment versus prophylaxis when administered at a dose of 100 IU/kg once weekly, the annualized bleed rate (ABR) for the prophylaxis period was significantly lower (P <0.0001) than the ABR for the on-demand period (mean ± standard deviation (SD): 3.6 ± 4.6, median: 2.0, min-max: 0-13.8 vs mean: 32.9 ± 17.4, median: 33.6, min-max: 6.1-69.0, respectively).
In an open-label crossover trial in patients aged 6-64 years, of 100 IU/kg once weekly (44 patients) and 50 IU/kg twice weekly (43 patients) with 4-month treatment periods, the ABR for the 100 IU/kg once-weekly prophylaxis period was mean 4.4 ± 10.0 episodes per year (median: 0.0, min-max: 0–50.5) and mean 2.8 ± 5.7 (median: 0.0, min-max: 0–24.1) for the 50 IU/kg twice-weekly period.
Adults and Children:
See full labeling. Initial Dose Required (IU) = Body Weight (kg) x Desired FIX increase x Reciprocal of observed recovery (IU/kg per IU/dL). Average recovery (≥12yrs): Dose Required (IU) = Body Weight (kg) x Desired FIX increase x 1.3 (IU/kg per IU/dL); (<12yrs): Dose Required (IU) = Body Weight (kg) x Desired FIX increase x 1.4 (IU/kg per IU/dL). Give by IV infusion over several minutes. If inhibitor present or low factor IX recovery, may need higher doses. Hemorrhage (Minor): 20–30% increase every 12–24hrs for 1–2 days; (Moderate): 25–50% increase every 12–24hrs for 2–7 days until resolved; (Major): 50–100% increase every 12–24hrs for 7–10 days. Routine prophylaxis (≥16yrs): 100 IU/kg once weekly; adjust dose or frequency based on clinical response.
BENEFIX Contraindications:
Hamster protein hypersensitivity.
BENEFIX Warnings/Precautions:
Safety and efficacy as continuous infusion: not established. Perform initial (approx. 10–20) administrations under medical supervision. Monitor closely for acute hypersensitivity reactions (esp. during the early phases); discontinue immediately if occurs and treat appropriately. Monitor for development of factor IX inhibitors; increased risk of anaphylaxis. Pregnancy. Nursing mothers.
BENEFIX Classification:
Clotting factor.
Adverse Reactions:
Fever, cough, nausea, inj site reaction/pain, headache, dizziness, rash; hypersensitivity reactions, inhibitor development, thromboembolic complications, nephrotic syndrome.
Generic Drug Availability:
NO
How Supplied:
Kit—1 (vial + diluent, supplies)
