Kcentra®, from CSL Behring, Receives FDA Approval for Use in Warfarin Reversal
in Patients Undergoing Surgery
New Kcentra Label Includes Urgent Reversal of Warfarin in an Emergency Surgery
KING OF PRUSSIA, Pa., Dec. 13, 2013
KING OF PRUSSIA, Pa., Dec. 13, 2013 /PRNewswire/ -- CSL Behring today
announced that Kcentra^® (Prothrombin Complex Concentrate [Human]) has
received U.S. Food and Drug Administration (FDA) approval for an expanded
indication -- urgent reversal of acquired coagulation factor deficiency
induced by vitamin K antagonist (VKA, e.g., warfarin) therapy in adult
patients needing an urgent surgery or other invasive procedure. Kcentra,
approved by the FDA in April 2013 for the urgent reversal of warfarin therapy
in adult patients with acute major bleeding, is the only non-activated
4-factor prothrombin complex concentrate (4F-PCC) indicated in the U.S. for
"When patients who are taking warfarin require an urgent surgical or invasive
procedure, it is critical to quickly restore their coagulation status," said
Joshua N. Goldstein, M.D., Ph.D., Department of Emergency Medicine,
Massachusetts General Hospital. "Kcentra is an important new option for such
cases; it does not require blood-type matching or thawing, and restores
clotting factors more quickly than plasma. We anticipate that emergency
physicians, surgeons and other hospital clinicians will welcome the expanded
Kcentra helps restore blood coagulation by replenishing the levels of clotting
factors that were depleted by warfarin therapy. Kcentra contains four vitamin
K-dependent factors: Factor II (prothrombin), Factor VII, Factor IX and Factor
X, as well as antithrombotic Proteins C and S.
Warfarin is used each year by approximately three to four million people in
the U.S. to prevent blood clots from forming following a stroke, heart attack,
heart valve surgery, deep vein thrombosis/pulmonary embolism, or certain types
of irregular heartbeat, such as atrial fibrillation.^, Due to the
deficiency in blood clotting factors induced by warfarin treatment, patients
are at increased risk of bleeding, especially if undergoing an urgent surgery
or invasive procedure.
"At CSL Behring, we are committed to improving the lives of people with
serious health conditions by continuously working to address unmet medical
needs with novel therapies," said Lynne Powell, Senior Vice President, North
America Commercial Operations, CSL Behring. "The expanded indication for
Kcentra in patients on warfarin therapy needing an urgent surgery or invasive
procedure is another example of this commitment."
About the Urgent Surgery/Invasive Procedure Clinical Trial
The prospective, randomized, Phase IIIb study used as the basis for the FDA
approval of the expanded indication for Kcentra included 168 evaluable
patients on Vitamin K antagonist therapy, e.g., warfarin, who required urgent
replacement of their Vitamin K-dependent clotting factors due to the need for
an urgent surgery/invasive procedure. Kcentra was superior to plasma in
achieving the endpoints of hemostatic efficacy for the time period from the
start of infusion of Kcentra or plasma until the end of the urgent surgery or
other invasive procedure (89.7 percent of patients treated with Kcentra versus
75.3 percent treated with plasma) and INR reduction (to less than or equal to
1.3) at 30 minutes after the end of infusion (55.2 percent of patients treated
with Kcentra versus 9.9 percent of patients treated with plasma).
The secondary endpoints included plasma levels of major clotting factors
(Factors II, VII, IX, X, antithrombotic proteins C and S) and safety and
tolerability (including all-cause mortality). A single Kcentra infusion
produced a rapid and sustained increase in plasma levels of clotting Factors
II, VII, IX, and X within 30 minutes after the end of infusion with 89 percent
less volume (90 mL +/-32 mL versus 819 mL +/- 231 mL) than plasma.
Additionally, infusion time with Kcentra was nearly seven times faster than
with plasma (21 minutes versus 141 minutes for plasma).
Kcentra had a safety profile comparable to plasma. The most common adverse
reactions (frequency greater than or equal to 2.8%) observed in patients
receiving Kcentra in both the Acute Major Bleeding Study and the Urgent
Surgery/Invasive Procedure study were headache, nausea/vomiting, hypotension
and anemia. The most serious adverse reactions were thromboembolic events
including stroke, pulmonary embolism and deep vein thrombosis.
In more than 25 countries, CSL Behring markets Kcentra as Beriplex^® or
In December 2012, the FDA granted Orphan Drug Designation for Kcentra for the
treatment of patients needing urgent reversal of Vitamin K antagonist therapy
due to major bleeding and/or surgical procedures. The FDA's Orphan Drug
Designation program provides orphan status to unique drugs and biologics
defined as those intended for the safe and effective treatment or prevention
of rare diseases that affect fewer than 200,000 people in the U.S. Orphan
designation qualifies the sponsor of the product for important tax credits,
elimination of FDA license application fees and certain marketing incentives.
Important Safety Information
Kcentra^®, Prothrombin Complex Concentrate (Human), is a blood coagulation
factor replacement product indicated for the urgent reversal of acquired
coagulation factor deficiency induced by Vitamin K antagonist (VKA -- e.g.,
warfarin) therapy in adult patients with acute major bleeding or the need for
urgent surgery or other invasive procedure. Kcentra is for intravenous use
WARNING: ARTERIAL AND VENOUS THROMBOEMBOLIC COMPLICATIONS
Patients being treated with Vitamin K antagonist therapy have underlying
disease states that predispose them to thromboembolic events. Potential
benefits of reversing VKA should be weighed against the risk of thromboembolic
events, especially in patients with history of such events. Resumption of
anticoagulation therapy should be carefully considered once the risk of
thromboembolic events outweighs the risk of acute bleeding. Both fatal and
nonfatal arterial and venous thromboembolic complications have been reported
in clinical trials and postmarketing surveillance. Monitor patients receiving
Kcentra, and inform them of signs and symptoms of thromboembolic events.
Kcentra was not studied in subjects who had a thromboembolic event, myocardial
infarction, disseminated intravascular coagulation, cerebral vascular
accident, transient ischemic attack, unstable angina pectoris, or severe
peripheral vascular disease within the prior 3 months. Kcentra might not be
suitable for patients with thromboembolic events in the prior 3 months.
Kcentra is contraindicated in patients with known anaphylactic or severe
systemic reactions to Kcentra or any of its components (including heparin,
Factors II, VII, IX, X, Proteins C and S, Antithrombin III and human albumin).
Kcentra is also contraindicated in patients with disseminated intravascular
coagulation. Because Kcentra contains heparin, it is contraindicated in
patients with heparin-induced thrombocytopenia (HIT).
Hypersensitivity reactions to Kcentra may occur. If patient experiences severe
allergic or anaphylactic type reactions, discontinue administration and
institute appropriate treatment.
In clinical trials, the most frequent (greater than or equal to 2.8%) adverse
reactions observed in subjects receiving Kcentra were headache,
nausea/vomiting, hypotension, and anemia. The most serious adverse reactions
were thromboembolic events, including stroke, pulmonary embolism and deep vein
Kcentra is derived from human plasma. The risk of transmission of infectious
agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease
(CJD) agent, cannot be completely eliminated.
The safety and efficacy of Kcentra in pediatric use have not been studied, and
Kcentra should be used in women who are pregnant or nursing only if clearly
For more information about Kcentra, please visit www.kcentra.com or call
toll-free 1-855-4KCENTRA. For full prescribing information, please visit
About CSL Behring
CSL Behring is a leader in the plasma protein therapeutics industry. Committed
to saving lives and improving the quality of life for people with rare and
serious diseases, the company manufactures and markets a range of
plasma-derived and recombinant therapies worldwide.
CSL Behring therapies are used around the world to treat coagulation disorders
including hemophilia and von Willebrand disease, primary immune deficiencies,
hereditary angioedema and inherited respiratory disease, and neurological
disorders in certain markets. The company's products are also used in cardiac
surgery, organ transplantation, burn treatment and to prevent hemolytic
diseases in the newborn. CSL Behring operates one of the world's largest
plasma collection networks, CSL Plasma. CSL Behring is a subsidiary of CSL
Limited (ASX: CSL), a biopharmaceutical company headquartered in Melbourne,
Australia. For more information, visit www.cslbehring.com.
Senior Manager, Public Relations & Communications
 Zareh M, Davis A, Henderson S. Reversal of warfarin-induced hemorrhage in
the emergency department. West J Emerg Med. 2011;12(4):386-392.
 Raife TJ, Rose JS, Lentz SR. Bleeding from acquired coagulation defects
and antithrombotic therapy. In: Simon TL, Snyder EL, Stowell CP, Strauss RG,
Solheim BG, Petrides M, eds. Rossi's Principles of Transfusion Medicine. 4th
ed. Hoboken, NJ: Wiley Blackwell; 2009; chapter 24.
SOURCE CSL Behring
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