Pharmacologic class: Clotting factor
Active ingredient: Antihemophilic Factor (recombinant): nominally 250 IU, 500 IU, 1,000 IU, or 2,000 IU per vial; powder for IV infusion after reconstitution; plasma/ albumin-free; preservative-free; contains polysorbate 80. Actual factor VIII activity noted on each vial.
Indication: In hemophilia A: to control bleeding episodes, and for surgical prophylaxis.
Pharmacology: Hemophilia A is a disease in which the patient is deficient in the coagulation factor VIII, a pivotal protein in the clotting cascade. The administration of Xyntha to patients with hemophilia A can temporarily correct the coagulation defect by increasing plasma factor VIII activity.
Xyntha uses a mammalian cell line to produce a factor VIII glycoprotein in cell culture without using any materials derived from human or animal sources. After a series of purification steps, it is treated with a solvent/detergent viral inactivation step and a virus-retaining nanofiltration step. The amino acid sequence of the factor VIII glycoprotein in Xyntha is comparable to the 90 + 80 kiloDalton form of human Factor VIII; it does not contain the B-domain. One international unit (IU) of factor VIII approximates the activity of factor VIII in 1 mL of normal human plasma.
Clinical trials: The efficacy of this product was evaluated in a study in which patients received Xyntha on a prophylaxis treatment regimen with on-demand treatment given as clinically indicated. This study enrolled 94 patients with baseline factor VIII activity <2%. They all received Xyntha in the open-label period, and 53 were given Xyntha for treatment of 187 bleeding episodes. Most of the bleeding episodes resolved with one or two infusions. In an ongoing, open-label study of Xyntha in surgical prophylaxis, an interim analysis showed that for 21 surgical patients, the investigators’ ratings of efficacy at the end of surgery and at the end of the initial post-op period were excellent or good for all assessments.
Adults: Individualize and titrate. Give by IV infusion over several minutes. One IU of factor VIII per kg raises the plasma factor VIII activity by about 2 IU/dL. To determine dose: Required units = body wt (kg) x desired factor VIII rise (IU/dL or % of normal) x 0.5 (IU/kg per IU/dL). Minor bleeds: Factor VIII level required is 20-40 IU/dL or % of normal, repeat infusion every 12-24 hours as needed for at least one day, until resolution. Moderate bleeds: 30-60 IU/dL or % of normal; repeat infusion every 12-24 hours for three to four days or until hemostasis. Major bleeds: 60-100 IU/dL or % of normal, repeat infusion every 8-24 hours until resolution. Minor surgical procedures: 30-60 IU/dL or % of normal, repeat infusion every 12-24 hours for three to four days or until hemostasis. Major surgery: 60-100 IU/dL or % of normal; repeat infusion every 8-24 hours until hemostasis and wound healing occurs.
Children: Consult manufacturer (limited pharmacokinetic data available; studies are ongoing).
Precautions: Use only under the supervision of a properly trained physician. Monitor for development of neutralizing antibodies (“inhibitors”); may need dose adjustment. Pregnancy (Cat. C). Labor and delivery. Nursing mothers.
Adverse reactions: Hypersensitivity reactions/anaphylaxis, pyrexia, headache, GI upset, asthenia.
How supplied: Kit—1 (with diluent, supplies).
For more information, call 800.934.5556 or visit www.Xyntha.com.