Coagulation Factor IX Recombinant for Injection

Name: Coagulation Factor IX Recombinant for Injection

Indications

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

Limitations of Use

BeneFIX is NOT indicated for:

  • 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.

How supplied

Dosage Forms And Strengths

BeneFIX is supplied as a white lyophilized powder in the following dosages:

  • 250 IU
  • 500 IU
  • 1000 IU
  • 2000 IU
  • 3000 IU

BeneFIX, Coagulation Factor IX (Recombinant), is supplied in kits that include single-use vials which contain nominally 250, 500, 1000, 2000, or 3000 IU per vial (NDC 58394-633-03, 58394-634-03, 58394-635-03, 58394-636-03 and 58394-637-03, respectively) with sterile pre-filled diluent syringe, vial adapter reconstitution device, sterile infusion set, and two (2) alcohol swabs, one bandage, and one gauze pad. Actual factor IX activity in IU is stated on the label of each vial.

Storage And Handling

Product Kit as Packaged for Sale
  • Store BeneFIX at room temperature or under refrigeration, at a temperature of 2 to 30°C (36 to 86°F).
  • Do not freeze to prevent damage to the diluent syringe.
  • Do not use BeneFIX after the expiration date on the label.
Product After Reconstitution

The product does not contain a preservative and should be used within 3 hours.

Manufactured by: Wyeth Pharmaceuticals Inc., A subsidiary of Pfizer Inc., Philadelphia, PA 19101. Revised: Sep 2015

Side effects

The most serious adverse reactions are systemic hypersensitivity reactions, including bronchospastic reactions and/or hypotension and anaphylaxis and the development of high-titer inhibitors necessitating alternative treatments to factor IX replacement therapy.

The most common adverse reactions observed in clinical trials (frequency > 5% of PTPs or PUPs) were headaches, dizziness, nausea, injections site reaction, injection site pain and skin-related hypersensitivity reactions (e.g., rash, hives).

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.

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. These adverse reactions are summarized in Table 2.

Table 2: Adverse Reactions Reported for PTPs*

Body System Adverse Reaction Number of patients (%)
Blood and lymphatic system disorders Factor IX inhibition† 1 (1.5%)
Eye disorders Blurred vision 1 (1.5%)
Gastrointestinal disorders Nausea 4 (6.2%)
Vomiting 1 (1.5%)
General disorders and administration
site conditions
Injection site reaction 5 (7.7%)
Injection site pain 4 (6.2%)
Fever 2 (3.1%)
Infections and infestations Cellulitis at IV site 1 (1.5%)
Phlebitis at IV site 1 (1.5%)
Headache 7 (10.8%)
Dizziness 5 (7.7%)
Nervous system disorders Taste perversion (altered taste) 3 (4.6%)
Shaking 1 (1.5%)
Drowsiness 1 (1.5%)
Renal and urinary disorders Renal infarct‡ 1 (1.5%)
Respiratory, thoracic and mediastinal
disorders
Dry cough 1 (1.5%)
Hypoxia 1 (1.5%)
Chest tightness 1 (1.5%)
Skin and subcutaneous disorders Rash 4 (6.2%)
Hives 2 (3.1%)
Vascular disorders Flushing 2 (3.1%)
*Adverse reactions reported within 72 hours of an infusion of BeneFIX.
†Low-titer transient inhibitor formation.
‡The renal infarct developed in a hepatitis C antibody-positive patient 12 days after a dose of BeneFIX for a bleeding episode. The relationship of the infarct to the prior administration of BeneFIX is uncertain.

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. These events are summarized in Table 3.

Table 3: Adverse Reactions Reported for PUPs*

Body System Adverse Reaction Number of Patients (%)
Blood and lymphatic system disorders Factor IX inhibition† 2 (3.2%)
General disorders and administration site Injection site reaction 1 (1.6%)
conditions Chills 1 (1.6%)
Respiratory, thoracic and mediastinal disorders Dyspnea (respiratory distress) 2 (3.2%)
Skin and subcutaneous disorders Hives 3 (4.8%)
Rash 1 (1.6%)
*Adverse reactions reported within 72 hours of an infusion of BeneFIX.
†Two subjects developed high-titer inhibitor formation during treatment with BeneFIX.

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).

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 (see Table 2). Laboratory studies of thrombogenecity (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.

Postmarketing Experience

The following post-marketing adverse reactions have been reported for BeneFIX: inadequate factor IX recovery, inadequate therapeutic response, inhibitor development [see CLINICAL PHARMACOLOGY], anaphylaxis [see WARNINGS AND PRECAUTIONS], angioedema, dyspnea, hypotension, and thrombosis.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

There have been post-marketing reports of thrombotic events, including life-threatening SVC syndrome in critically ill neonates, while receiving continuous-infusion BeneFIX through a central venous catheter. Cases of peripheral thrombophlebitis and DVT have also been reported. In some, BeneFIX was administered via continuous infusion, which is not an approved method of administration [see DOSAGE AND ADMINISTRATION]. The safety and efficacy of BeneFIX administration by continuous infusion have not been established [see WARNINGS AND PRECAUTIONS].

Warnings

Included as part of the PRECAUTIONS section.

Where can i get more information?

Your pharmacist can provide more information about coagulation factor IX.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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