BeneFIX - Wyeth - Marketed Lyophilized Drug Products

Has BeneFIX been used to successfully prevent bleeding in a surgical setting?
In clinical trials, BeneFIX has been used to treat 12 patients who underwent 13 different surgical procedures, including liver transplantation, a hernia repair, six orthopedic surgeries, and two dental extractions.8 Preoperative doses ranged from 25 to 155 IU/kg and postoperative doses from 30 to 169 IU/kg.17 Hemostasis was maintained throughout the surgical period; however, one patient required evacuation of a surgical wound site hematoma, and another patient who received BeneFIX after a tooth extraction required further surgical intervention due to oozing at the extraction site.8 Ninety-seven percent of the clinical responses during surgery were rated as excellent or good by either the surgeon or investigator or (when appropriate) by the patient.16
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Has the development of inhibitors been a problem with BeneFIX?
Of 56 patients receiving BeneFIX, one previously treated patient developed a low-level, low-responding inhibitor. Two of 59 previously untreated patients developed a high-titer inhibitor.
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What are the most common side effects of BeneFIX?
BeneFIX is indicated for the control and prevention of hemorrhagic episodes in patients with hemophilia B (congenital factor IX deficiency or Christmas disease), including control and prevention of bleeding in surgical settings.
BeneFIX is not indicated for the treatment of other factor deficiencies (eg, factors II, VII, VIII and X) nor the treatment of hemophilia A patients with inhibitors to factor VIII, nor the reversal of coumarin-induced anticoagulation, nor the treatment of bleeding due to low levels of liver-dependent coagulation factors.
As with the intravenous administration of any protein product, common adverse reactions may include headache, fever, chills, flushing, nausea, vomiting, or tiredness. Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported for all factor IX products. Patients should be informed of the early symptoms and signs of hypersensitivity reactions. Patients should discontinue use of the product and contact their health care provider immediately and/or seek emergency care if any hypersensitivity reactions occur. BeneFIX may be contraindicated in patients with a known history of hypersensitivity to hamster protein. The accompanying diluent vial may contain dry natural rubber that may cause hypersensitivity reactions in persons with known or possible latex sensitivity.
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How do I dose BeneFIX compared with plasma-derived products?
Dosage and duration of treatment for all factor IX products depend on the severity of the factor IX deficiency, the location and extent of bleeding, and the patient's clinical condition, age, and recovery of factor IX. To ensure that the desired factor IX activity level has been achieved, precise monitoring using the factor IX activity assay is advised. Doses should be titrated using the factor IX activity, pharmacokinetic parameters, such as half-life and recovery, as well as taking the clinical situation into consideration in order to adjust the dose as appropriate.
In the clinical efficacy studies, patients were initially administered the same dose previously used for plasma-derived factor IX. Even in the absence of a factor IX inhibitor, approximately half of the patients increased their dose of BeneFIX during these studies. Titrate the initial dose upward if necessary to achieve the desired clinical response. As with some plasma-derived factor IX products, patients at the low end of the observed factor IX recovery may require upward dosage adjustment to as much as two times the initial empirically calculated dose in order to achieve the intended rise in circulating factor IX activity.
In adult PTPs, on average, 1 IU of BeneFIX per kg body weight increased the circulating activity of factor IX by 0.8 ? 0.2 (ranged from 0.3 to 1.4) IU/dL. The method of dose estimation is illustrated in the following example:
Adult Patients

number of
factor IX IU
required (IU) = body
weight
(kg) X desired factor IX
increase
(% or IU/dL) X 1.2
(IU/kg
per IU/dL)
In pediatric patients (< 15 years of age), on average, 1 IU of BeneFIX per kg body weight increased the circulating activity of factor IX by 0.7 ? 0.2 (ranged from 0.3 to 1.1) IU/dL.
The method of dose estimation is illustrated in the following example:
Pediatric Patients (<15 years)
number of
factor IX IU required (IU) = body
weight
(kg) X desired factor IX
increase
(% or IU/dL) X 1.4
(IU/kg
per IU/dL)
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How is BeneFIX administered?
After reconstitution with Sterile Water for Injection (diluent), BeneFIX is administered by intravenous (IV) infusion following procedures similar to commercially available plasma-derived factor IX products.
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What is the shelf life of BeneFIX?
BeneFIX should be stored under refrigeration at a temperature of 36? to 46? F (2? to 8? C). Prior to the expiration date, BeneFIX may be stored at room temperature (77? F or 25? C) for up to 6 months. To prevent damage to the diluent vial, freezing should be avoided.
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How soon must BeneFIX be administered after reconstitution?
Because BeneFIX does not contain a preservative, it should be used within 3 hours after reconstitution. BeneFIX should not be used after the expiration date on the label.