Dosing & Uses
Dosage Forms & Strengths
lyophilized concentrate for reconstitution
- 500 units/vial
- 1000 units/vial
Vitamin K Antagonist Reversal
Indicated for urgent reversal of acquired coagulation factor deficiency induced by vitamin K antagonists (VKA, eg, warfarin) therapy in adults with acute major bleeding or need for an urgent surgery/invasive procedure
Individualize dosing based on patient’s current pre-dose INR value and body weight
Administer vitamin K concurrently to maintain vitamin K-dependent clotting factor levels once the effects of prothrombin complex concentrate have diminished
Repeat dosing is not supported by clinical data and is not recommended
Dosing guidelines
- Based on pretreatment INR obtained close to time of dosing (coagulation factor levels may be unstable in patients with acute major bleeding who are receiving Vitamin K)
- Dose in units below is based on factor IX content in product
- INR 2 to <4: 25 units/kg IV; not to exceed 2500 units
- INR 4-6: 35 units/kg IV; not to exceed 3500 units
- INR >6: 50 units/kg IV; not to exceed 5000 units
Example dosing calculation
- For 80 kg patient with INR 5.0: 35 units/kg x 80 kg = 2800 units
- For vial with actual potency of 30 units/mL Factor IX, 93 mL would be administered (2800 units ÷ 30 units/mL = 93 mL)
Composition/vial
- Actual potency per vial of Factors II, VII, IX, and X, and proteins C and S is stated on carton
-
Kcentra 500-mL vial
- Total protein: 120-280mg
- Factor II: 380-800 units
- Factor VII: 200-500 units
- Factor IX: 400-620 units
- Factor X: 500-1020 units
- Protein C: 420-820 units
- Protein S: 240-680 units
- Heparin: 8-40 units
- Antithrombin III: 4-30 units
- Human albumin: 40-80mg
- NaCl: 60-120mg
- Sodium citrate: 40-80mg
- Buffering agents (HCl, NaOH): Small amounts
-
Balfaxar 500-mL vial
- Factor II: 340-500 units
- Factor VII: 240-500 units
- Factor IX: 400-640 units
- Factor X: 300-560 units
- Protein C: 320-560 units
- Protein S: 240-600 units
- Heparin: 8-384 units
- Sodium citrate: 16.8-23.4 mmol/L
Dosing Considerations
Not indicated for urgent reversal of VKA anticoagulation in patients without acute major bleeding
Unlike plasma, does not require blood group typing or thawing, so it can be administered more quickly than frozen plasma
Administered in a significantly lower volume than plasma at recommended doses, providing an alternative for volume restricted patients
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (17)
- alteplase
alteplase, prothrombin complex concentrate, human. pharmacodynamic synergism. Contraindicated.
- anti-inhibitor coagulant complex
anti-inhibitor coagulant complex increases effects of prothrombin complex concentrate, human by pharmacodynamic synergism. Contraindicated. Coadministration increases risk of thrombosis.
- apixaban
apixaban, prothrombin complex concentrate, human. pharmacodynamic antagonism. Contraindicated.
- argatroban
argatroban, prothrombin complex concentrate, human. pharmacodynamic antagonism. Contraindicated.
- bivalirudin
bivalirudin, prothrombin complex concentrate, human. pharmacodynamic synergism. Contraindicated.
- dabigatran
dabigatran, prothrombin complex concentrate, human. pharmacodynamic synergism. Contraindicated.
- dalteparin
dalteparin, prothrombin complex concentrate, human. pharmacodynamic antagonism. Contraindicated.
- enoxaparin
enoxaparin, prothrombin complex concentrate, human. pharmacodynamic antagonism. Contraindicated.
- Factor IX
Factor IX increases effects of prothrombin complex concentrate, human by pharmacodynamic synergism. Contraindicated. Coadministration increases risk of thrombosis.
- Factor IX, recombinant
Factor IX, recombinant increases effects of prothrombin complex concentrate, human by pharmacodynamic synergism. Contraindicated. Coadministration increases risk of thrombosis.
- Factor VIIa, recombinant
Factor VIIa, recombinant increases effects of prothrombin complex concentrate, human by pharmacodynamic synergism. Contraindicated. Coadministration increases risk of thrombosis.
- heparin
heparin, prothrombin complex concentrate, human. pharmacodynamic antagonism. Contraindicated.
- protein C concentrate
protein C concentrate increases effects of prothrombin complex concentrate, human by pharmacodynamic synergism. Contraindicated. Coadministration increases risk of thrombosis.
- reteplase
reteplase, prothrombin complex concentrate, human. pharmacodynamic antagonism. Contraindicated.
- rivaroxaban
rivaroxaban, prothrombin complex concentrate, human. pharmacodynamic antagonism. Contraindicated.
- tenecteplase
tenecteplase, prothrombin complex concentrate, human. pharmacodynamic antagonism. Contraindicated.
- tranexamic acid injection
tranexamic acid injection increases effects of prothrombin complex concentrate, human by pharmacodynamic synergism. Contraindicated. Coadministration increases risk of thrombosis.
Serious - Use Alternative (0)
Monitor Closely (3)
- dichlorphenamide
dichlorphenamide and prothrombin complex concentrate, human both decrease serum potassium. Use Caution/Monitor.
- emicizumab
prothrombin complex concentrate, human, emicizumab. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Thrombotic microangiopathy reported when aPCC was coadministered with emicizumab. Patients presented with thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury, without severe deficiencies in ADAMTS13 activity. Thromboembolism was also reported with coadministration.
- Factor X, human
Factor X, human, prothrombin complex concentrate, human. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Caution is advised in patients who are receiving other plasma products that may contain Factor X, (eg, fresh frozen plasma, prothrombin complex concentrates).
Minor (0)
Adverse Effects
>10%
Kcentra
- Procedural pain (48.5%)
- Asthenia (17.5%)
- Postoperative wound complication (14.6%)
- Thromboembolic events, TE history (11.6%)
Balfaxar
- Procedural pain (47.6%)
- Postoperative wound complication (14.3%)
- Catheter site related reaction (12.4%)
- Asthenia (12.4%)
1-10%
Kcentra
- Hypotension (7.3%)
- Headache (7.3%)
- Nausea/vomiting (6.3%)
- Anemia (5.8%)
- Abdominal pain (4.9%)
- Blood pressure increased (4.9%)
- Hypokalemia (4.7%)
- Tachycardia (4.7%)
- Atrial fibrillation (4.2%)
- Pleural effusion (4.2%)
- Skin laceration/contusion/ hematoma (4.2%)
- Suture related complication (3.9%)
- Body temperature increased (3.9%)
- Respiratory distress/dyspnea/hypoxia (3.7%)
- Thromboembolic event, no TE history (2.9%)
- Fluid overload (2.6%)
- Diarrhea (2.1%)
- Cather site related reaction (1.9%)
- Dysuria (1.9%)
- Pulmonary edema (1.6%)
Balfaxar
- Anemia (5.7%)
- Dysuria (4.8%)
- Catheter site related reaction (3.8%)
- Procedural vomiting (3.8%)
- Abdominal pain (2.9%)
- Thromboembolic events (2.9%)
- Suture related complication (1.9%)
- Unstable angina (1%)
Postmarketing Reports
Kcentra
- Hypersensitivity or allergic reactions: Flushing, urticaria, tachycardia, anxiety, angioedema, wheezing, nausea, vomiting, hypotension, tachypnea, dyspnea, pulmonary edema, and bronchospasm
- Thromboembolic complications: Arterial thromboembolic events (including acute MI and arterial thrombosis), venous thromboembolic events (including PE and venous thrombosis), and DIC
Balfaxar
- Immune system disorders: Anaphylactic shock, anaphylactic reaction, anaphylactoid reaction, hypersensitivity reaction
- Nervous system disorders: Cerebrovascular accident, headache, paresthesia, tremor
- Cardiac disorders: Bradycardia, tachycardia, cardiac arrest
- Vascular disorders: Thromboembolic events, circulatory collapse, hypotension, hypertension
- Respiratory, thoracic, and mediastinal disorders: Dyspnea, respiratory failure
- Gastrointestinal disorders: Nausea
- Skin and subcutaneous tissue disorders: Urticaria, rash, pruritus
- General disorders and administration site conditions: Fever, chills
Warnings
Black Box Warnings
Patients being treated with vitamin K antagonists (VKA) have underlying disease that predispose them to thromboembolic events; potential benefits of reversing VKA should be weighed against the potential risks of thromboembolic events
Both fatal and nonfatal arterial and venous thromboembolic complications reported during clinical trials and postmarketing surveillance; monitor for signs and symptoms
Not studied in individuals who had a thromboembolic event, MI, DIC, CVA, TIA, unstable angina, or severe PVD within the prior 3 months before administration
Contraindications
Anaphylaxis or severe systemic reactions to any component
Known heparin-induced thrombocytopenia (HIT; product contains heparin)
Kcentra
- Disseminated intravascular coagulation (DIC)
Balfaxar
- IgA deficiency with known antibodies against IgA
Cautions
Hypersensitivity reactions reported, including flushing, urticaria, tachycardia, anxiety, angioedema, wheezing, nausea, vomiting, hypotension, tachypnea, dyspnea, pulmonary edema, and bronchospasm
Thromboembolic risk/complications
- Fatal and nonfatal arterial and venous thromboembolic complications reported (see Black Box Warnings)
- Reversing VKA therapy, due to thromboembolic complications, exposes patients to thromboembolic risk of their underlying disease; once the risk of thromboembolic events outweighs the risk of acute bleeding, resumption of anticoagulation should be carefully considered following administration of Kcentra and Vitamin K
- Because of risk of thromboembolism associated with reversal of VKA, closely monitor patients for signs and symptoms of thromboembolism during and after therapy administration
Transmissible infectious agent
- Made from human blood; risk of transmitting infectious agents (eg, viruses including hepatitis and HIV, Creutzfeldt-Jakob variant or disease)
- Report all infections thought by a physician to have been possibly transmitted by prothrombin complex concentrate to CSL Behring Pharmacovigilance Department at 1-866-915-6958 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
Pregnancy & Lactation
Pregnancy Category: C
Lactation: Unknown whether distributed in human breast milk; breast feeding not advised
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Contains vitamin-K-dependent coagulation Factors II, VII, IX, and X, together known as prothrombin complex and the antithrombotic protein C and protein S
A dose-dependent acquired deficiency of vitamin K-dependent coagulation factors occurs during vitamin K antagonist treatment; vitamin K antagonists exert anticoagulant effects by blocking carboxylation of glutamic acid of vitamin K-dependent coagulation factors during hepatic synthesis, lowering both factor synthesis and function
Administration of prothrombin complex rapidly increases plasma levels of coagulation factors and the anti-thrombotic proteins
Median INR before treatment (3.0) dropped to median value of 1.2 at 30 minutes after starting infusion (in contrast to plasma which dropped to 2.4 after 30 minutes)
Coagulation factors MOA
- Factor II (prothrombin) is converted to thrombin by activated FX (FXa) in the presence of Ca2+, FV, and phospholipids
- Factor VII (proconvertin) is converted to the activated form (FVIIa) by splitting of an internal peptide link; FVIIa-TF complex activates factor IX and initiates the primary coagulation pathway by activating FX in the presence of phospholipids and calcium ions
- Factor IX (antihemophilic globulin B, or Christmas factor) is activated by the FVIIa-TF complex and by FXIa; factor IXa in the presence of FVIIIa activates FX to FXa
- Factor X (Stuart-Prower factor) activation involves the cleavage of a peptide bond by the FVIIIa-factor IXa complex or the TF-FVIIa complex; factor Xa forms a complex with activated FV (FVa) that converts prothrombin to thrombin in the presence of phospholipids and calcium ions
- Protein C, when activated by thrombin, exerts an antithrombotic effect by inhibiting FVa and FVIIIa leading to a decrease in thrombin formation, and has indirect profibrinolytic activity by inhibiting plasminogen activator inhibitor-1
- Protein S exists in a free form (40%) and in a complex with C4b-binding protein (60%); the free form functions as a cofactor for activated protein C in the inactivation of FVa and FVIIIa, leading to antithrombotic activity
Pharmacokinetics
AUC (IU/dL x hr)
- Factor IX: 1490
- Factor II: 6577
- Factor VII: 424
- Factor X: 6707
- Protein C: 5276
- Protein S: 3667
Vd (mL/kg)
- Factor IX: 92.4
- Factor II: 71.0
- Factor VII: 41.8
- Factor X: 56.1
- Protein C: 62.9
- Protein S: 76.6
Half-life, terminal (hr)
- Factor IX: 16.7
- Factor II: 59.7
- Factor VII: 4.2
- Factor X: 30.7
- Protein C: 47.2
- Protein S: 49.1
Administration
IV Preparation
Ensure lyophilized powder and diluent vials are at room temperature before reconstitution
Refer to prescribing information for full instructions
Reconstitute vial with 20 mL of diluent provided in kit using Mix2Vial transfer set provided (see package instructions)
Visually inspect reconstituted vial for particulate matter and discoloration; it should be colorless, clear to slightly opalescent, and free from visible particles
Do not use solutions that are cloudy or have deposits
For single use only, contains no preservatives
Discard partially used vials
When reconstituted, final concentration of drug product in Factor IX units will range between 20-31 units/mL (depending on actual potency listed on the carton)
IV Administration
Reconstituted solution should be at room temperature before infusing
Do not mix with other medicinal products
Administer through a separate infusion line
No blood should enter the syringe, as there is a possibility of fibrin clot formation
Infuse IV at rate of 0.12 mL/kg/min (~3 units/kg/min), up to maximum rate of 8.4 mL/min (~210 units/min)
Record product lot number in patient’s medical record
Storage
Unopened vialsº
- Stable until date indicated on package (36 months from manufacture date)
- Store between 2-25°C [36-77°F]) in original carton and protect from light
- Do not freeze
Reconstituted vials
-
Kcentra
- Use within 4 hr following reconstitution
- Store between 2-25°C (36-36-77°F)
- If cooled, the solution should be warmed to 20-25°C before administration
- Do not freeze
- Discard partially used vials
-
Balfaxar
- Store at room temperature (20-25ºC [68-77ºF])
- Use within 8 hr after reconstitution
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Kcentra intravenous - | 500 unit (400-620 unit) vial |  |
Copyright © 2010 First DataBank, Inc.
Patient Handout
human prothrombin complex (PCC) 4-factor intravenous
NO MONOGRAPH AVAILABLE AT THIS TIME
USES: Consult your pharmacist.
HOW TO USE: Consult your pharmacist.
SIDE EFFECTS: Consult your pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Consult your pharmacist.
DRUG INTERACTIONS: Consult your pharmacist.Keep a list of all your medications with you, and share the list with your doctor and pharmacist.
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.
NOTES: No monograph available at this time.
MISSED DOSE: Consult your pharmacist.
STORAGE: Consult your pharmacist.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.
Information last revised July 2016. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
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