Urgent warfarin reversal

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About warfarin and warfarin reversal

Warfarin is used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic complications associated with atrial fibrillation and/or cardiac valve replacement. Warfarin is also approved for reduction in the risk of death, recurrent myocardial infarction, and thromboembolic events such as stroke or systemic embolization after myocardial infarction.1 Unfortunately, the most common adverse reaction to warfarin is hemorrhage,1 which is associated with hospital stays, transfusions, endoscopy, surgery, and ICU admission.2 When selecting a warfarin reversal agent, the efficacy and time to INR reduction should be considered.4 While physicians may be comfortable with fresh frozen plasma (FFP),4 FFP has presented its own set of risks, namely fluid overload, which is associated with higher total hospital costs and longer hospital and ICU lengths of stay as compared with individuals without fluid overload.5

As an alternative, KCENTRA offers superior* and sustained INR reduction and faster administration, with approximately 85% less volume vs plasma in pivotal trials. In the pivotal trials, there were 9 subjects (4.7%) in the KCENTRA group who experienced fluid overload; all were deemed non–treatment-related. Twenty-five subjects (12.7%) in the FFP group experienced fluid overload; 13 were deemed treatment-related.

KCENTRA offers superior, early INR reduction vs FFP.6,7*

The relationship between INR values and clinical hemostasis in patients has not been established.

ICU, intensive care unit; INR, international normalized ratio.

What is KCENTRA?

KCENTRA is a blood coagulation factor replacement product indicated for the urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonist (VKA, eg, warfarin) therapy in adult patients with acute major bleeding or need for an urgent surgery/invasive procedure.

KCENTRA is for intravenous use only.

Please see full prescribing information for KCENTRA.
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What are the key benefits?

KCENTRA is the #1 prescribed 4F-PCC with the longest record of proven safety and efficacy since 2013

Faster acting icon

FASTER ACTING*

Superior INR reduction at 30 minutes after end of infusion vs plasma6,7

Sustained INR reduction icon

SUSTAINED INR,
REDUCTION†

Statistically significant INR reduction sustained ≤1.3 for up to 8 hours in the Urgent Surgery trial and 12 hours in the Acute Major Bleeding trial6,7

Faster administration lower volume icon

FASTER ADMINISTRATION,
LOWER VOLUME

Mean infusion time is under 25 minutes; ~85% less volume vs plasma6,7

In the largest study to date on 4F-PCC TE events and all-cause mortality, KCENTRA demonstrated no increased risk of TE events and 41% risk reduction in adjusted all-cause mortality vs plasma.8

4F-PCC, 4-factor prothrombin complex concentrate; TE, thromboembolic.

*In 2 head-to-head trials, KCENTRA demonstrated superiority to plasma in 3 of 4 efficacy endpoints. Superior hemostatic efficacy in the Urgent Surgery/Invasive Procedures trial and equally effective hemostasis in the Acute Major Bleeding trial. Faster INR reduction (to ≤1.3 at 30 minutes after end of infusion) in both head-tohead trials.

†8 hours for Urgent Surgery/Invasive Procedures trial and 12 hours for Acute Major Bleeding trial. Administer vitamin K concurrently to patients receiving KCENTRA. Vitamin K is administered to maintain vitamin K–dependent clotting factor levels once the effects of KCENTRA have diminished.

The value of KCENTRA

The hospital cost of KCENTRA was lower than plasma9

Patients treated with KCENTRA cost 34% ($18K) less than patients treated with plasma for the duration of hospital stay

Cost for hospitalization per patient, overall

Cost of hospitalization per patient

FDA, US Food and Drug Administration.

Costs refer to the expenses incurred by healthcare providers in delivering medical services or treatments.

Costs include the cost of treatment (plasma or KCENTRA). Costs can be further broken down by department of billing: surgery, room and board, pharmacy,

professional fees, laboratory, blood bank, etc.

Between January 2016 and December 2020, over 550,000 patients with a bleed were identified in the PINC Al Healthcare Database.

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Important Safety Information

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 (≥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 thrombosis.

KCENTRA is derived from human plasma. The risk of transmission of infectious agents, including viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent and its variant (vCJD), cannot be completely eliminated.

Indications

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—eg, warfarin) therapy in adult patients with acute major bleeding or the need for urgent surgery or other invasive procedure. KCENTRA is for intravenous use only.

Please see full prescribing information for KCENTRA.

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To report SUSPECTED ADVERSE REACTIONS, contact the CSL Behring Pharmacovigilance Department at 1-866-915-6958 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

References: 1. Coumadin. Prescribing information. Bristol-Myers Squibb Company; 2017. 2. Guerrouij M, Uppal CS, Alklabi A, Douketis JD. The clinical impact of bleeding during oral anticoagulant therapy: assessment of morbidity, mortality and post-bleed anticoagulant management. J Thromb Thrombolysis. 2011;31(4):419-423. doi:10.1007/s11239-010-0536-7 3. Frontera JA, Lewin JJ 3rd, Rabinstein AA, et al. Guideline for reversal of antithrombotics in intracranial hemorrhage: executive summary. A statement for healthcare professionals from the Neurocritical Care Society and the Society of Critical Care Medicine. Crit Care Med. 2016;44(12):2251-2257. doi:10.1097/CCM.0000000000002057 4. Data on file. Available from CSL Behring as DOF KCT-004. 5. Magee G, Zbrozek A. Fluid overload is associated with increases in length of stay and hospital costs: pooled analysis of data from more than 600 US hospitals. Clinicoecon Outcomes Res. 2013;5:289-296. doi:10.2147/CEOR.S45873 6. Goldstein JN, Refaai MA, Milling TJ Jr, et al. Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial. Lancet. 2015;385(9982):2077-2087. doi:10.1016/S0140-6736(14)61685-8 7. Sarode R, Milling TJ Jr, Refaai MA, et al. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding: a randomized, plasma-controlled, phase IIIb study. Circulation. 2013;128(11):1234-1243. doi:10.1161/CIRCULATIONAHA.113.002283 8. Go AS, Leong TK, Sung SH, et al. Thromboembolism after treatment with 4-factor prothrombin complex concentrate or plasma for warfarin-related bleeding. J Thromb Thrombolysis. 2022;54(3):470-479. doi:10.1007/s11239-022-02695-5 9. Data on file. Available from CSL Behring as DOF KCT-011.

KCENTRA is manufactured by CSL Behring GmbH and distributed by CSL Behring LLC.
KCENTRA® is a registered trademark of CSL Behring GmbH.
©2025 CSL Behring LLC. The product information presented on this page is intended for US residents only.
USA-KCT-0318-MAR25

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