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Patients with atrial fibrillation or an artificial heart valve often need long-term anticoagulation to reduce their high risk for thrombotic events. Warfarin and other vitamin K antagonist (VKA) anticoagulants can prevent thrombosis, but there is an increased risk of major bleeding.
Human prothrombin complex concentrate can be used more quickly than plasma for reversal of VKA anticoagulation, as it can be used without blood group typing or thawing. This therapy offers clinicians a new option for patients requiring urgent reversal of VKA anticoagulation.
The US Food and Drug Administration (FDA) approved a plasma-derived product for the urgent reversal of VKA anticoagulation in adults with acute major bleeding, the agency announced.
The new therapy, prothrombin complex concentrate, human (Kcentra), addresses the problem of acute bleeding sometimes experienced by patients with atrial fibrillation or an artificial heart valve who receive long-term anticoagulation therapy with warfarin and other VKA anticoagulants to prevent blood clotting.
Prothrombin complex concentrate, human, can be used more quickly than plasma to reverse the effect of VKA anticoagulants. Unlike plasma, it does not require blood group typing or thawing. In addition, it is administered in a far lower volume than plasma at recommended doses, which is good news for patients who may not tolerate the amount of plasma needed to stop the bleeding, said Karen Midthun, MD, director of the FDA's Center for Biologics Evaluation and Research.
"The FDA's approval of this new product gives physicians a choice when deciding how to treat patients requiring urgent reversal of VKA anticoagulation," said Dr. Midthun.
As with plasma, prothrombin complex concentrate, human, is given together with vitamin K.
The FDA based its approval on a study of 216 individuals receiving VKA anticoagulation. The study showed that the new therapy resembled plasma in its ability to stop acute major bleeding.
A boxed warning on the label states that there is a risk for blood clots. Clinicians should monitor patients receiving the product for signs and symptoms of thromboembolic events.
Derived from the pooled plasma of healthy donors, prothrombin complex concentrate, human, is processed to minimize the risk of transmitting viral and other diseases, the FDA stated.
Dosage and Administration
Human prothrombin complex concentrate comes in a single-use vial containing coagulation factors II, VII, IX, and X, and antithrombotic proteins C and S as a lyophilized concentrate.
Human prothrombin complex concentrate is intended for intravenous use only, to be given concurrently with vitamin K to maintain factor levels once the effects of human prothrombin complex concentrate have diminished. Clinical data do not support repeated dosing, which is therefore not recommended.
On the basis of the patient's pretreatment international normalized ratio (INR), dosing is individualized to 25 to 50 units of factor IX per kg body weight, up to but not exceeding 100 kg. Therefore, the maximal dose must not exceed 5000 units of factor IX. Another variable that must be considered in dosing is actual potency, which is stated on the carton and varies from 20 to 31 factor IX units per mL Nominal potency is 500 units per vial, approximately 25 units per mL after reconstitution.
The rate of administration of reconstituted human prothrombin complex concentrate should begin at a rate of 0.12 mL per kg per minute (approximately 3 units per kg per minute), with the maximal rate not to exceed of 8.4 mL per minute (approximately 210 units per minute).
Warnings, Precautions, and Adverse Reactions
If hypersensitivity reactions occur, administration should be discontinued and the patient treated appropriately.
Patients receiving human prothrombin complex concentrate should be monitored for signs and symptoms of arterial and venous thromboembolic events.
Because human prothrombin complex concentrate has not been studied in patients who had a thrombotic or thromboembolic event within the prior 3 months, it may not be suitable for such patients.
There is a theoretical risk of transmitting the variant Creutzfeldt-Jakob disease agent, the Creutzfeldt-Jakob disease agent, and other viruses.
Headache, nausea or vomiting, joint pain, and hypotension are the most common adverse reactions reported in patients receiving human prothrombin complex concentrate, occurring in 2.8% or more. Thromboembolic events including stroke, pulmonary embolism, and deep vein thrombosis were the most serious adverse reactions.
More information on the FDA decision is available on the agency's Web site.
Laurie Barclay, MD, has contributed to the synopsis.
