prothrombin complex concentrate, human

Action and Spectrum

Drug Interaction

Adverse Reaction

Frequency defined 

1-10% 

Headache (7.8%) 

Nausea/vomiting (3.9%) 

intracranial Hemorrhage (2.9%) 

Increased BP (2.9%) 

Dyspnea/Respiratory distress/hypoxia (1.9%) 

Fluid overload (1%) 

Chest pain (1%) 

Thromboembolic events (8.7%) 

Hypotension (4.9%) 

Arthralgia (3.9%) 

Mental status (2.9%) 

contusion/Skin laceration/hematoma (2.9%) 

Constipation (1.9%) 

abnormal rates, Breath sounds (1%) 

Insomnia (1%)  

Post marketing Reports 

allergic or hypersensitivity reactions: urticaria, anxiety, wheezing, vomiting, tachypnea, pulmonary edema, Flushing, tachycardia, angioedema, nausea, hypotension, dyspnea, and bronchospasm
Thromboembolic complications: venous thromboembolic events, Arterial thromboembolic events 

Black Box Warning

Black Box Warning: 

prothrombin complex concentrate, human does not have a specific black box warning. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Known hypersensitivity or allergic reaction to any component of the product. 
• Disseminated intravascular coagulation (DIC) with bleeding. 
• Known hereditary or acquired thrombophilia or a history of thromboembolic events unless the potential benefit outweighs the risk. 
• Active major bleeding, including intracranial hemorrhage. 
• Known hypersensitivity or intolerance to heparin, factors II, VII, IX, or X, or other vitamin K-dependent factors.

Caution: 

• History of thromboembolic events, including deep vein thrombosis, pulmonary embolism, or myocardial infarction. 
• Risk factors for thromboembolic events, such as obesity, advanced age, immobilization, or history of clotting disorders. 
• Patients with liver disease or impaired liver function, as prothrombin complex concentrate, human contains factors dependent on liver synthesis. 
• Renal impairment, as prothrombin complex concentrate, human may contain small amounts of heparin, which can accumulate in patients with renal dysfunction. 
• Hypertension or other cardiovascular conditions, as prothrombin complex concentrate, human can increase the risk of thromboembolic events.

Comorbidities: 

• Thromboembolic disorders: Patients with a history of thromboembolic events, such as deep vein thrombosis (DVT), pulmonary embolism (PE), or myocardial infarction (MI), may be at an increased risk of recurrent events when receiving prothrombin complex concentrate, human. Close monitoring and consideration of the risks versus benefits are important. 
• Cardiovascular diseases: Patients with pre-existing cardiovascular conditions, such as coronary artery disease, heart failure, or hypertension, may have an increased risk of thromboembolism when receiving prothrombin complex concentrate, human. Careful evaluation of the individual’s cardiovascular status and risk factors is necessary. 
• Liver disease: prothrombin complex concentrate, human contains factors dependent on liver synthesis. Therefore, patients with severe liver disease or impaired liver function may have altered coagulation profiles and may require dose adjustments or careful monitoring during treatment. 
• Renal impairment: prothrombin complex concentrate, human may contain small amounts of heparin, which can accumulate in patients with renal dysfunction. Close monitoring of coagulation parameters and renal function is recommended in such cases. 
• Allergic or hypersensitivity reactions: Individuals with a known hypersensitivity or intolerance to prothrombin complex concentrate, human or any of its components should avoid its use. 

Pregnancy / Lactation

Pregnancy consideration: FDA pregnancy category: C 

Lactation: Excreted into human milk: Unknown  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence when combined with risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence when combined with risk when combined with adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care when combined with potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence when combined with human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories when combined with drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

• Coagulation factors: PCC contains various clotting factors, including factor II (prothrombin), factor VII, factor IX, and factor X. These factors work together to promote the formation of fibrin, which is essential for blood clotting. 
• Vitamin K-dependent factors: Some of the clotting factors in PCC, such as factor II, VII, IX, and X, are vitamin K-dependent. They require adequate levels of vitamin K for their synthesis and activity. PCC provides these factors in their active form, allowing for immediate clotting factor replacement. 
• Hemostasis restoration: PCC works by replenishing deficient clotting factors in patients with coagulation disorders. It helps restore hemostasis by promoting the formation of a stable clot and preventing or stopping bleeding episodes. 
• Reversal of anticoagulant effects: PCC can be used to reverse the effects of certain anticoagulant medications, such as vitamin K antagonists (e.g., warfarin) or direct oral anticoagulants (DOACs). By providing concentrated clotting factors, PCC can counteract the anticoagulant effects and restore normal coagulation. 
• Rapid onset of action: PCC has a rapid onset of action due to its immediate availability of clotting factors. This allows for prompt correction of coagulation abnormalities and faster control of bleeding. 
• Individualized dosing: The dose of PCC is determined based on the patient’s specific coagulation profile, severity of bleeding, and underlying condition. It is important to consider factors such as the patient’s weight, baseline clotting factor levels, and the desired degree of hemostatic correction.

Pharmacodynamics: 

• Clotting factor replacement: PCC contains clotting factors II (prothrombin), VII, IX, and X, which are essential for the stable blood clot fonrmatio. These factors work together to activate the coagulation cascade and promote clot formation at the site of vascular injury. 
• Correction of coagulation abnormalities: PCC is used to replenish deficient clotting factors in patients with bleeding disorders or those requiring urgent reversal of anticoagulant therapy. By providing concentrated clotting factors, PCC helps correct coagulation abnormalities and restore normal hemostasis. 
• Accelerated clot formation: PCC facilitates the rapid formation of fibrin, the protein network that strengthens the blood clot. The clotting factors in PCC activate the conversion of fibrinogen to fibrin, leading to the formation of a stable clot and prevention or cessation of bleeding. 
• Reversal of anticoagulant effects: PCC can be employed to reverse the anticoagulant effects of certain medications, such as vitamin K antagonists (e.g., warfarin) or direct oral anticoagulants (DOACs). By providing an abundance of clotting factors, PCC helps counteract the anticoagulant activity and restore normal clotting function. 
• Individualized response: The pharmacodynamics of PCC can vary between individuals based on factors such as the underlying bleeding disorder, severity of coagulopathy, and the patient’s baseline clotting factor levels. The response to PCC administration is tailored to the specific needs of the patient, and dosing is adjusted accordingly. 

Pharmacokinetics: 

Absorption 

PCC is administered intravenously, directly into the bloodstream. As a result, the medication is rapidly and completely absorbed. 

Distribution 

Once in the bloodstream, PCC distributes throughout the body. The clotting factors present in PCC circulate within the blood and reach various tissues and organs. 

Metabolism 

PCC does not undergo significant metabolism in the body. Instead, the clotting factors in PCC act directly on the coagulation cascade to promote clot formation. 

Elimination and excretion 

The excretion of PCC primarily occurs through the normal physiological processes of blood clearance. The individual clotting factors in PCC have their own specific half-lives and clearance rates, which may vary. However, PCC does not undergo significant renal or hepatic excretion. 

Adminstartion

Administration: 

• Preparation: PCC usually comes in a powdered form and requires reconstitution with sterile water or another compatible diluent. The reconstitution process should be performed according to the manufacturer’s instructions. 
• Dosage: The dosage of PCC is determined based on the specific indication, patient characteristics (such as weight and coagulation parameters), and the healthcare professional’s judgment. The dosage may vary for each individual, and it is important to follow the prescribed dose. 
• Route of administration: PCC is administered intravenously, usually through a peripheral vein or a central line. The infusion rate should be controlled according to the recommended guidelines. 
• Infusion duration: The duration of the PCC infusion can vary depending on the indication and the specific patient situation. It is important to follow the recommended infusion time specified in the prescribing information or as directed by the healthcare professional. 
• Monitoring: During the administration of PCC, close monitoring of the patient’s vital signs, coagulation parameters, and any signs of adverse reactions is necessary. This includes monitoring for allergic reactions, thromboembolic events, or any other potential complications. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: prothrombin complex concentrate, human 

Pronounced: (pro-throm-bin com-plex con-cent-rate, hyoo-man)  

Why do we use prothrombin complex concentrate, human? 

• Reversal of Vitamin K antagonist anticoagulation: PCC can be used to rapidly reverse the effects of vitamin K antagonists in patients who require urgent correction of their coagulation status. 
• Treatment of bleeding or hemorrhage: PCC may be used to manage acute bleeding or hemorrhage in patients with coagulation factor deficiencies, such as hemophilia or other congenital bleeding disorders. 
• Management of surgical bleeding: PCC can be used in surgical settings to control or prevent excessive bleeding, especially in patients with known or suspected coagulation factor deficiencies. 
• Treatment of coagulopathy due to liver disease: PCC may be used in patients with liver disease who develop coagulopathy due to impaired synthesis of clotting factors. 
• Reversal of direct oral anticoagulants (DOACs): In certain situations, PCC can be used to reverse the anticoagulant effects of DOACs, such as dabigatran, rivaroxaban, apixaban, or edoxaban, in cases of life-threatening bleeding or urgent surgical procedures.