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.

16 comments:

  1. Any thoughts about what weight calculation to use (i.e., if total body weight is >1.2xIBW perhaps using Adjusted Body Weight is best, but if actual body weight is less than 1.2xIBW, any thoughts on just using actual body weight versus ideal body weight for these patients? Although, we would always round up or down to nearest vial size with corresponding units when using Bebulin or Profilnine, in some cases this translates into using an additional vial or not using one which has huge cost implications. Thank you.

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    1. What we do currently with Profilnine is use a maximum dose of 2500 units and 5000 units for the 25 unit/kg and 50 unit/kg doses, respectively. We also have the pharmacists round up or down to the nearest vial size. We'll most likely be doing the same with Kcentra.

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  2. Any idea as to when this will be available?

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    1. It will be available sometime in June. The price: 1.27$ per unit

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    2. Where did you find this information? When our procurement pharmacist looked into this a couple of weeks ago he said he couldn't find anything yet.

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    3. This information is from the Kcentra PI and direct communication with CSL Behring

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    4. I am a pharmacy student doing some research on this medication and I was hoping one of you could clarify. When you say $1.27/unit do you mean $1.27 per vial or $1.27 per unit dosed (25units/kg x $1.27 = $31.75/kg)?

      Thanks

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  4. I also called CSL Behring and I was told the price for Kcentra would be $1.27/unit. However, I was told it would be available in July.

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  5. The package insert for KCENTRA indicates that the randomized trial comparing KCENTRA to FFP resulted in deaths in 9.7% of those on KCENTRA compared to 4.6% on FFP. What are your thoughts on these numbers? Do you think comparing PCC to FFP is a fair comparison for a randomized trial? Thanks,

    Kevin

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  6. Is anyone going to add this to formulary to replace their current 3 factor PCC + FFP protocol? Kcentra has not been studied as multiple doses, but the European product has. It seems there is not a clinical benefit vs 3 factor PCC and FFP.

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  7. Do you know where I can find the phase 3 clinical trials? I have searched everywhere. Surely there is a website that directs one to them. Thank you.

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  8. RE: replacing 3FPCC+FFP with this 4FPCC -- we are not going to do it. I'm not convinced the extra cost is necessary. 25unit/kg profilnine +/- a couple units of FFP quickly drops INRs even above 4. I've not been convinced that the extra cost of a higher indicated # units/kg AND higher cost per unit is necessary. Besides that, I like the ability to use 3 factor PCC alone when INR is low (ie 2-4) and still adequately drop INR without the likely excess thrombosis risk from additional factor VII in FFP. -- Pharmacist at ~250 bed hospital in PA

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    1. Would your opinion change with a Jehovah's Witness patient with an INR well above 4? That's what I'm chewing on.
      Pharmacist at ~150 bed in WA

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    2. In that patient population, aside from not receiving any blood products, 3/4 factor PCCs play a role. I unfortunately do not have experience treating many of those types of patients but, utilizing these products with other volume expanders may be options.

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    3. PCC's are still made from human plasma. Would that patient even accept the PCC?

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