Tuesday, April 30, 2013

Fast Facts About Kcentra, The "New" Four-Factor PCC in the United States


Here are some fast facts clinicians should be aware of regarding Kcentra:
  • Kcentra is marketed in over 25 countries around the world by CSL Behring as Beriplex® or Confidex®.
  • It is four-factor PCC, containing factors II, VII, IX, and X, in varying amounts, based on the size of the vial. It also contains Proteins C and S as well as heparin and antithrombin III. The table below provides a breakdown of the contents per 500 units of Kcentra, which comes out to approximately 25 mL upon reconstitution: 
  • The final concentration of factor IX per vial upon reconstitution ranges from 20 to 31 units/mL
  • Kcentra has currently been approved in the United States for the reversal of life-threatening hemorrhage secondary to warfarin.
  • The weight-based dosing regimen of Kcentra is based on the initial INR. The dose is maximized as follows in patients weighing greater than 100 kg 
    • INR of 2 to less than 4: 25 units/kg (maximum dose: 2500 units)
    • INR of 4 to 6: 35 units/kg (maximum dose: 3500 units)
    • INR of greater than 6: 50 units/kg (maximum dose: 5000 units)
  • The manufacturer does not recommend re-dosing Kcentra, as this has not been evaluated in clinical trials.
  • Vitamin K (phytonadione) should be administered along with Kcentra to sustain the levels of vitamin K-dependent clotting factors.  
  • The recommended rate of administration of Kcentra is 0.12 mL/kg/min (approximately 3 units/kg/min), up to a maximum rate of 8.4 mL/min (210 units/min) via IV infusion.
  • In terms of storage and shelf life:
    • Should be stored at temperatures between 2 and 25°C (36 to 77°F).
    • Stable for 36 months from the date of manufacture, up to the expiration date on the packaging of the product.
    • After reconstitution, the product is stable for 4 hours. 
  • As could be expected, adverse events associated with the use of Kcentra include thromboembolic complications; those reported from the clinical trials include myocardial infarction, deep vein thrombosis, and cerebrovascular accidents. 
  • Other common adverse events that patients experienced in the clinical trials of Kcentra include arthralgia (3.9%), headache (7.8%), hypotension (4.9%), and nausea and vomiting (3.9%).  
  • The clinical trials of Kcentra excluded those patients with a history of thromboembolic events occurring within the previous three months; use of Kcentra is not recommended in this patient population. 
Stay tuned for future posts regarding Kcentra, including a review of the clinical trials as well as the incorporation of the product into our practice.

Reference:
1.  Kcentra (prothrombin complex concentrate [human]) [package insert]. CSL Behring, LLC; 2013.