Limiting Off-label use of KCentra in High Value Warfarin Therapy

From the 2018 HVPAA National Conference

Stanley Podlasek (Johns Hopkins Department of Pathology), Robert Linton (Johns Hopkins Department of Emergency Medicine), Swetha Paluru (Johns Hopkins Department of Pathology), Isha John (Howard County General Hospital), Adrienne Shepardson (Howard County General Hospital), Christina Mancini-Flegel (Johns Hopkins Department of Radiology), Shafeeq Ahmed (Johns Hopkins Hospital), Eric Aldrich (Howard County General Hospital), Clarita Dawson (Howard County General Hospital), Cheryl Burruss (Howard County General Hospital), Karen Wilson (Howard County General Hospital), Lexi Bryant (Howard County General Hospital), Paul Ness (Johns Hopkins School of Medicine), Eric Gehrie (Johns Hopkins Department of Pathology), Steven Frank (Johns Hopkins Hospital)


Warfarin effect is easily reversed by holding doses or by administration of vitamin K.   For urgent reversal, KCentra (4 factor PCC made from US plasma donors) is FDA approved.  Evidence to support OFF-label use of 4 factor PCC is not robust (National Drug Monograph, VA Pharmacy Benefits Management Services, 2015).


Limit OFF-label use of KCentra.


With introduction of KCentra into the formulary of our 267 bed community hospital in December 2016, the pharmacy and therapeutics committee decided to limit KCentra to ON-label use. Up until the introduction of a stroke-center program at our facility, fresh frozen plasma and vitamin K were considered sufficient for warfarin reversal.  This stroke program, plus the limited availability of fresh frozen plasma in deference to plasma frozen within 24 hours, lead to the introduction of KCentra for rapid warfarin reversal in patients with acute intracranial hemorrhage.

The pharmacy reviews all orders for KCentra, most from the hospital Emergency Department. Those orders for patients on warfarin with acute intracranial hemorrhage are released without delay.  OFF-label orders are referred to the hospital blood bank, and blood bank contacts the transfusion medicine pathologist on call for prospective approval of OFF-label requests.


This program has been in place for 16 months. In the first 7 months (16 Dec – 16 June) 42% (5/12) requests were OFF label, and in the most recent 7 months (16 July – 18 Jan) 44% (4/9) requests were OFF-label.  The OFF-label KCentra actually given in the first 7 months of the program was 33% (4/12), and in the most recent 7 months 11% (1/9).

Overall 43% (9/21) of orders are for OFF-label use, but only 24% (5/21) of KCentra was given for an OFF-label indication.  Cancellation of the order by the provider or refusal to approve the order by the pathologist account for this difference.  Patients initially considered for KCentra, but who did not receive it, suffered no adverse effects.


Prospective evaluation of requests for KCentra is effective in limiting use to evidence based indications. Warfarin is less costly and more easily reversed than novel anticoagulants making it the high value antithrombotic therapy.

Implications for the Patient

  • KCentra is not routinely administered to reverse warfarin effect.
  • Intracranial hemorrhage and uncontrolled life-threatening hemorrhage are ON-label uses for KCentra to achieve warfarin reversal.
  • Prospective review of selective orders limits OFF-label use of KCentra.
  • KCentra should be administered only once with vitamin K.

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