Section 13 · Monograph
Prothrombin complex concentrate (4F-PCC)
Reviewed Nov 2026FDA label
KcentraClotting factor concentrate (boxed warning: thromboembolism)
- Forms
- IV: lyophilized powder, 500 and 1000 unit vials
- Dose
- Warfarin reversal by INR: 25 units/kg (INR 2 to <4, max 2500) | 35 units/kg (INR 4-6, max 3500) | 50 units/kg (INR >6, max 5000); DOAC reversal (off-label): 50 units/kg or 2000 units fixed; give with vitamin K
- MOA
- Replaces vitamin K-dependent factors II, VII, IX, X plus proteins C and S
Black Box Warning
- Arterial and venous thromboembolic complications, including fatal events, can occur; patients being treated with vitamin K antagonists have underlying thromboembolic risk — resume anticoagulation as soon as medically appropriate
Indications
- Urgent reversal of acquired coagulation factor deficiency from vitamin K antagonist therapy in adults with acute major bleeding or need for urgent surgery/invasive procedureFDA-labeled
Off-Label Uses
- Factor Xa inhibitor (apixaban, rivaroxaban) reversal at about 50 units/kg or a fixed dose of about 2000 units — used since andexanet alfa (Andexxa) was withdrawn from the US market in December 2025Off-label
Mechanism of Action
- Four-factor prothrombin complex concentrate replacing vitamin K-dependent factors II, VII, IX and X plus anticoagulant proteins C and S
- INR typically falls to 1.3 or lower within 30 minutes
Full Dosing
Adult / usual
- Dose is based on factor IX units, pretreatment INR and body weight (up to 100kg)
- INR 2 to <4: 25 units/kg (max 2500 units); INR 4-6: 35 units/kg (max 3500 units); INR above 6: 50 units/kg (max 5000 units)
- Infuse at 0.12mL/kg/min (about 3 units/kg/min) up to 8.4mL/min; give vitamin K concurrently
- Repeat dosing is not supported by clinical data
- Supplied as 500- and 1000-unit lyophilized vials; actual potency stated on carton
Contraindications
- Known anaphylactic or severe systemic reaction to Kcentra or its components (including heparin)
- Heparin-induced thrombocytopenia
- Disseminated intravascular coagulation
Drug Interactions
- Do not mix with other drugs; administer through a separate line
- Concurrent prothrombotic agents (tranexamic acid, activated PCC, recombinant factor VIIa) may increase thrombosis risk
Adverse Effects
- Thromboembolism (DVT, PE, MI, stroke)
- Headache, nausea, hypotension
- Infusion/hypersensitivity reactions
- Theoretical infectious risk (plasma-derived)
Monitoring Parameters
- INR before and about 30 minutes after dosing
- Signs of thrombosis
- Clinical bleeding control; fibrinogen and platelets as indicated
Pregnancy & Lactation
- Limited data; use only if benefit outweighs risk