Prothrombin and Water

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 need for an urgent surgery/invasive procedure.

KCENTRA contains the Vitamin K-dependent coagulation Factors II (FII), VII (FVII), IX (FIX), and X (FX), together known as the Prothrombin Complex, and the antithrombotic Protein C and Protein S. A dose-dependent acquired deficiency of the Vitamin K-dependent coagulation factors occurs during Vitamin K antagonist treatment. Vitamin K antagonists exert anticoagulant effects by blocking carboxylation of glutamic acid residues of the Vitamin K-dependent coagulation factors during hepatic synthesis, lowering both factor synthesis and function. The administration of KCENTRA rapidly increases plasma levels of the Vitamin K-dependent coagulation Factors II, VII, IX, and X as well as the antithrombotic Proteins C and S. Coagulation Factor II Factor II (prothrombin) is converted to thrombin by activated FX (FXa) in the presence of Ca 2+, FV, and phospholipids.

For intravenous use after reconstitution only. KCENTRA dosing should be individualized based on the patient's baseline International Normalized Ratio (INR) value, and body weight. Administer Vitamin K concurrently to patients receiving KCENTRA to maintain factor levels once the effects of KCENTRA have diminished. The safety and effectiveness of repeat dosing have not been established and it is not recommended. Administer reconstituted KCENTRA at a rate of 0.12 mL/kg/min (~3 units/kg/min) up to a maximum rate of 8.4 mL/min (~210 units/min). Pre-treatment INR 2–< 4 4–6 > 6 Dose Dosing is based on body weight. Dose based on actual potency is stated on the vial, which will vary from 20--31 Factor IX units/mL after reconstitution. The actual potency for 500 unit vial ranges from 400-620 units/vial.

KCENTRA is contraindicated in: Patients with known anaphylactic or severe systemic reactions to KCENTRA or any components in KCENTRA including heparin, Factors II, VII, IX, X, Proteins C and S, Antithrombin III and human albumin. Patients with disseminated intravascular coagulation (DIC). Patients with known heparin-induced thrombocytopenia (HIT). KCENTRA contains heparin. Disseminated intravascular coagulation. Known heparin-induced thrombocytopenia.

Boxed warning (arterial and venous thromboembolic complications): Patients being treated with Vitamin K antagonists (VKA) therapy have underlying disease states that predispose them to thromboembolic events. Potential benefits of reversing VKA should be weighed against the potential risks of thromboembolic events (TE), especially in patients with the history of a thromboembolic event. Hypersensitivity reactions may occur. If necessary, discontinue administration and institute appropriate treatment. Arterial and venous thromboembolic complications have been reported in patients receiving KCENTRA. Monitor patients receiving KCENTRA for signs and symptoms of thromboembolic events. KCENTRA was not studied in subjects who had a thrombotic or thromboembolic (TE) event within the prior 3 months. KCENTRA may not be suitable in patients with thromboembolic events in the prior 3 months.

The most common adverse reactions (ARs) (frequency ≥2.8%) observed in subjects receiving KCENTRA were headache, nausea/vomiting, hypotension, and anemia. The most serious ARs were thromboembolic events including stroke, pulmonary embolism, and deep vein thrombosis. The following serious adverse reactions are described below and/or elsewhere in the labeling: Hypersensitivity Reactions Arterial and venous thromboembolic complications Possible transmission of infectious agents The most common adverse reactions (ARs) (frequency ≥ 2.8%) observed in subjects receiving KCENTRA were headache, nausea/vomiting, hypotension, and anemia.

Store KCENTRA between 2–25°C (36–77°F), this includes room temperature, not to exceed 25°C (77°F). Do not freeze. If cooled, the solution should be warmed to 20–25°C prior to administration. Do not freeze. Store the vial in the original carton to protect it from light. Reconstituted KCENTRA can be stored at 2–25°C.