Brief Summary
See package insert for full Prescribing Information. For further product information and current package
insert, please visit www.BeneFix.com or call our medical communications department toll-free
at 1-800-438-1985.
INDICATIONS AND USAGE
BeneFix® Coagulation Factor IX (Recombinant), is a human blood coagulation factor indicated in adult
and pediatric patients with hemophilia B (congenital factor IX deficiency or Christmas disease) for:
• control and prevention of bleeding episodes
• peri-operative management
During uncontrolled open-label clinical studies with BeneFix conducted in previously treated patients
(PTPs), 113 adverse reactions with known or unknown relation to BeneFix therapy were reported
among 38.5% (25 of 65) of subjects (with some subjects reporting more than one event) who received
a total of 7,573 infusions. The most frequently reported treatment-emergent adverse reactions were
headache (10.8%), dizziness (7.7%), injection site reaction (7.7%), nausea (6.2%), and injection site
pain (6.2%).
In the 63 previously untreated patients (PUPs), who received a total of 5,538 infusions, 10 adverse
reactions were reported among 9.5% of the patients (6 out of 63) having known or unknown
relationship to BeneFix. Adverse reactions reported in ≥5% of subjects were: hives (4.8%), factor IX
inhibition (3.2%), dyspnea (3.2%), injection site reaction (1.6%), chills (1.6%), and rash (1.6%).
Limitations of Use
BeneFix is NOT indicated for:
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Clinical Trials Experience—Because clinical trials are conducted under widely varying conditions,
adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in
the clinical trials of another drug and may not reflect the rates observed in clinical practice.
treatment of other factor deficiencies (e.g., factors II, VII, VIII, and X),
treatment of hemophilia A patients with inhibitors to factor VIII,
reversal of coumarin-induced anticoagulation,
treatment of bleeding due to low levels of liver-dependent coagulation factors.
Immunogenicity
In clinical studies with 65 PTPs (defined as having more than 50 exposure days), a low-titer inhibitor
was observed in one patient. The inhibitor was transient, the patient continued on study and had
normal factor IX recovery pharmacokinetics at study completion (approximately 15 months after
inhibitor detection).
CONTRAINDICATIONS
BeneFix is contraindicated in patients who have manifested life-threatening, immediate hypersensitivity
reactions, including anaphylaxis, to the product or its components, including hamster protein.
WARNINGS AND PRECAUTIONS
Hypersensitivity Reactions
Hypersensitivity reactions, including anaphylaxis, have been reported with BeneFix and have
manifested as pruritus, rash, urticaria, hives, facial swelling, dizziness, hypotension, nausea, chest
discomfort, cough, dyspnea, wheezing, flushing, discomfort (generalized) and fatigue. Frequently,
these events have occurred in close temporal association with the development of factor IX inhibitors.
Closely monitor patients for signs and symptoms of acute hypersensitivity reactions, particularly during
the early phases of initial exposure to product. Because of the potential for allergic reactions with
factor IX concentrates, perform the initial (approximately 10 - 20) administrations of factor IX under
medical supervision where proper medical care for allergic reactions could be provided. Advise patients
to discontinue use of the product and contact their physician and/or seek immediate emergency care.
BeneFix contains trace amounts of hamster (CHO) proteins. Patients treated with this product may
develop hypersensitivity to these non-human mammalian proteins.
Thromboembolic Complications
There have been post-marketing reports of thrombotic events in patients receiving continuousinfusion BeneFix through a central venous catheter, including life-threatening superior vena cava (SVC)
syndrome in critically ill neonates. The safety and efficacy of BeneFix administration by continuous
infusion have not been established.
Nephrotic Syndrome
Nephrotic syndrome 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. The safety
and efficacy of using BeneFix for immune tolerance induction have not been established.
Neutralizing Antibodies (Inhibitors)
In clinical studies with pediatric PUPs, inhibitor development was observed in 2 out of 63 patients
(3.2%), both were high-titer (>5 BU) inhibitors detected after 7 and 15 exposure days, respectively.
Both patients were withdrawn from the study.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.
Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an
assay may be influenced by several factors, including assay methodology, sample handling, timing of
sample collection, concomitant medications, and underlying disease. For these reasons, comparison
of the incidence of antibodies to BeneFix with the incidence of antibodies to other products may
be misleading.
Thromboembolic complications
All subjects participating in the PTP, PUP and surgery studies were monitored for clinical evidence of
thrombosis. No thrombotic complications were reported in PUPs or surgery subjects. One PTP subject
experienced a renal infarct. Laboratory studies of thrombogenicity (fibrinopeptide A and prothrombin
fragment 1 + 2) were obtained in 41 PTPs and 7 surgery subjects prior to infusion and up to 24 hours
following infusion. The results of these studies were inconclusive. Out of 29 PTP subjects noted to
have elevated fibrinopeptide A levels post-infusion of BeneFix, 22 also had elevated levels at baseline.
Surgery subjects showed no evidence of significant increase in coagulation activation.
USE IN SPECIFIC POPULATIONS
Pregnancy
Pregnancy Category C—Animal reproduction and lactation studies have not been conducted with
BeneFix. It is not known whether BeneFix can affect