4-Factor Prothrombin Complex Concentrate (Kcentra)

ED / ICU / Transport

• Urgent warfarin (VKA) reversal for acute major bleeding: Kcentra's label covers it. Intracranial bleeding on a VKA is in this group too, and it runs on the stroke and neurocritical care protocol
• Urgent warfarin (VKA) reversal before urgent surgery or an invasive procedure: both labels cover this one
• Factor Xa inhibitor bleeding (apixaban, rivaroxaban, edoxaban) (off-label): 4F-PCC is the fallback when a specific reversal agent is unavailable. Vitamin K's role is warfarin-only, so see Vitamin K

Other Uses

• INR elevation without bleeding or a procedure (off-label): not a labeled use. The labels confine PCC to urgent bleeding or urgent surgery
• Balfaxar product limit: the label covers urgent surgery or an invasive procedure only. Acute major bleeding is not on it, so using it there is off-label

Doses vary by protocol; follow local protocols and medical direction.

Available Forms

• Kcentra 500-unit kit: single-dose vial, actual potency 400–620 units, with 20 mL sterile water (Mix2Vial)
• Kcentra 1,000-unit kit: single-dose vial, actual potency 800–1,240 units, with 40 mL sterile water (Mix2Vial)
• Balfaxar 500-unit vial: actual potency 400–640 units, reconstituted in 20 mL diluent; Balfaxar 1,000-unit vial: 800–1,280 units in 40 mL
• Read the actual potency off each carton or vial label. Dose from that number, not the nominal strength.

Adult Dosing

Pediatric Dosing

Preparation & Administration

• Reconstitution: use aseptic technique. Kcentra: 20 mL sterile water for the 500-unit kit, 40 mL for the 1,000-unit kit, through the Mix2Vial device. Balfaxar: same diluent volumes with its transfer device
• Dose volume: calculate from the actual potency per mL, not the nominal number (label example: 2,800 units at 30 units/mL = 93 mL)
• Rate: IV infusion by pump at 0.12 mL/kg/min (about 3 units/kg/min), maximum 8.4 mL/min (about 210 units/min)
• Hold time: start promptly after reconstitution; within 4 hours (Kcentra) or within 8 hours (Balfaxar), provided sterility is kept
• Line: give it on its own line and never mix it with other medicines. Balfaxar may be flushed with normal saline before and after. Keep blood out of the syringe, since blood brings a fibrin clot risk
• Vials: single-dose and preservative-free, so whatever is left goes in the bin. Pooling vials for one patient means a separate transfer device for each one
• Inspection: do not use if cloudy, discolored or containing particles. Give at room temperature

Contraindications

• Known anaphylactic or severe systemic reaction to the product or its components, including heparin, albumin and antithrombin
• Disseminated intravascular coagulation (DIC): Kcentra contraindication; for Balfaxar, monitor closely for DIC and thrombosis (warning, not contraindication)
• Known heparin allergy or heparin-induced thrombocytopenia (HIT); both Kcentra and Balfaxar contain heparin
• Balfaxar only: IgA deficiency with known antibodies against IgA

Precautions

• Recent thrombosis (relative): it was not studied within 3 months of a thromboembolic event, and it may not be suitable
• Coronary disease or liver disease: the Balfaxar label says to watch closely for thrombosis and DIC
• Hypersensitivity: reports include flushing, urticaria, angioedema, wheezing, hypotension and bronchospasm
• Plasma-derived product: because it comes from plasma, it may pass on infectious agents, including the vCJD agent

Hold / Reassess If

• Anaphylaxis or severe systemic reaction: stop the infusion and treat per protocol
• New stroke, MI, PE, DVT or limb ischemia: evaluate now and reassess before any anticoagulant restart
• INR still above the trial endpoint (1.3 Kcentra, 1.5 Balfaxar) 30 minutes after the infusion ends: that is a trial number, not a label target. Recheck INR, confirm vitamin K was given and reassess bleeding, because a corrected INR does not prove hemostasis. Repeat PCC is not label-recommended

Common

• Headache (about 7%), hypotension (about 7%), nausea or vomiting (about 6%) and anemia (about 6%); the most common reactions at 2.8% or higher in the Kcentra trials
• Tachycardia (about 5%) and atrial fibrillation (about 4%) in the same trial table

Serious / Life-Threatening

Andexanet figures: The FDA safety communication on ANNEXA-I puts thrombosis at 14.6% vs 6.9%, and thrombosis-related deaths at day 30 at 2.5% vs 0.9% (andexanet vs usual care). Those are not the trial-publication figures quoted in Clinical Pearls (10.3% vs 5.6%). Quote each number with the source named for it.

Overdose & Toxicity Management

• No specific antidote: the excess effect is mostly thrombotic, so treat the thrombosis per protocol
• Vitamin K is not an antidote to PCC: it keeps the liver making factors. Give it with PCC (see Vitamin K)
• Mortality signal: in the acute major bleeding trial, deaths ran 9.7% with Kcentra and 4.6% with plasma. The difference was not significant (95% CI −2.7% to 13.5%). Most of this risk comes from the underlying disease

Clinically Significant Interactions

IV Compatibility

• Give through a dedicated line; do not mix with other medicinal products (both labels)
• Balfaxar may be flushed with normal saline before and after the infusion
• Verify with an institutional compatibility resource.

• Pediatrics: neither label establishes safety or efficacy in children. Use it only with a specialist, and see the Pediatric Dosing table
• Neonates: the labels have no specific data for neonates, and the adult table does not cover them
• Pregnancy: the Kcentra label has no human or animal reproduction data. Use it only if clearly needed. Warfarin-related bleeding in pregnancy needs specialist input
• Lactation: the Kcentra label has no information on excretion into human milk. Use it only if clearly needed
• Older Adults: in the Kcentra studies, 66% of 431 patients were 65 or older and 39% were 75 or older. The studies reported no clinically significant safety difference by age
• Renal Impairment: neither label adjusts the dose for kidney function. Dosing runs on INR and weight
• Hepatic Impairment: in liver disease, the Balfaxar label says to monitor closely for thrombosis and DIC. No hepatic dose change is listed
• Obesity / Dosing Weight: dose on actual body weight, capped at 100 kg. Above 100 kg, the maximum applies
• IgA-Deficient Patients: Balfaxar is contraindicated when antibodies against IgA are present

• Scope: it varies by state and agency protocol. Most often it is given in the ED, the ICU or on hospital transport
• Storage & Stability: keep it at 2–25°C (36–77°F). Do not freeze it, and keep it in the original carton to protect it from light. Reconstituted, it holds for 4 hours (Kcentra) or 8 hours (Balfaxar)
• Carried Concentration: potency changes with the vial and the product (Kcentra 500-unit vial 400–620 units, Balfaxar 400–640 units). Confirm product name, actual units and volume at the pharmacy and at the bedside
• Infusions in Transport: run it by pump at 0.12 mL/kg/min (maximum 8.4 mL/min) on a dedicated line. Start the hold clock at reconstitution, plan the syringe or bag for the trip, and keep vitamin K ready
• Handoff Essentials: product name, actual units given, start and stop times, weight used, pre-dose INR and time, vitamin K time and dose, last warfarin or DOAC dose, thrombosis history and current bleeding status

Mechanism of Action

• Target: VKAs such as warfarin block carboxylation of vitamin K-dependent factors II, VII, IX and X, plus proteins C and S. Both their synthesis and their function drop
• Replacement: PCC supplies all four carboxylated factors at once. The high concentrations restore thrombin generation
• Anticoagulant proteins: the product also carries proteins C and S. They inhibit factors Va and VIIIa
• Clinical consequence: in most trial patients the INR falls within about 30 minutes, but INR is not a proven measure of hemostasis. Factor levels keep falling over days, so vitamin K is needed

Pharmacokinetics

• Half-life: Kcentra terminal half-lives in 15 healthy subjects: factor VII 5.0 hours, factor X 31.8 hours, factor IX 42.4 hours, protein C 49.6 hours, protein S 50.4 hours, factor II 60.4 hours. Factor VII clears fastest, which is one reason the INR can rebound before the other factors fall
• Metabolism: the factors are plasma proteins, cleared through normal protein turnover. No cytochrome P450 metabolism is involved
• Active metabolites: none
• Elimination: the labels describe nothing beyond the factor kinetics. They make no renal or hepatic dose adjustment

Generic Name

Prothrombin complex concentrate (human), 4-factor (4F-PCC)

Brand Names (US)

Kcentra (CSL Behring; approved 2013); Balfaxar (Octapharma; approved 2023)

Pharmacologic Class

Plasma-derived coagulation factor complex (vitamin K-dependent factors II, VII, IX, X and proteins C and S)

Therapeutic Class

Hemostatic agent; VKA reversal agent

Controlled Substance

Not controlled

ISMP High-Alert

No. Not on the ISMP List of High-Alert Medications in Acute Care Settings (2024 edition, checked 2026-10-15). Its antithrombotic class covers anticoagulants, DOACs and thrombolytics, not 4F-PCC

Look-Alike / Sound-Alike

None commonly reported. Kcentra and Balfaxar differ in indication and INR endpoint, so do not substitute by name alone

Error-Prone Abbreviations to Avoid

"PCC" alone: write "4F-PCC" (4-factor) or "aPCC" (activated PCC, a different product with different dosing)