Protein C Concentrate (Monograph)

Brand name: Ceprotin
Drug class: Anticoagulants, Miscellaneous

Medically reviewed by Drugs.com on Jun 22, 2023. Written by ASHP.

Introduction

Anticoagulant; a vitamin K-dependent serine protease precursor prepared from pooled human plasma.¹

Uses for Protein C Concentrate

Congenital Protein C Deficiency

Replacement therapy in patients with severe congenital protein C deficiency for prevention and treatment of venous thrombosis and purpura fulminans^{1 6} (designated an orphan drug by FDA for this use).²

Protein C Concentrate Dosage and Administration

General

• Dosage and duration of therapy is dependent on the severity of protein C deficiency, the plasma protein C concentration, and the patient’s age and clinical condition.¹

• Individualize dosage based on measured protein C activity, expressed as a percentage of normal plasma protein C concentrations, and adjust according to the pharmacokinetic profile for each individual patient.¹

• Determine plasma protein C concentrations before and during therapy using a chromogenic assay to measure protein C activity.¹

• During acute thrombotic episodes, measure protein C activity immediately before administration until the patient is stabilized and continue monitoring afterward.¹ The magnitude of increase in plasma protein C activity may be substantially reduced during acute episodes.¹

• Monitor coagulation parameters; however, correlation between levels of protein C activity and coagulation parameters not yet established.¹

Administration

IV Administration

Administer by IV injection.^{1 6}

Initiate therapy under supervision of a clinician experienced in replacement therapy with coagulation factors/inhibitors and where monitoring of protein C activity is feasible.^{1 6}

Protein C (human) may be self-administered if clinician determines that the patient and/or caregiver is competent to safely administer the drug after appropriate training.^{1 5 6}

Reconstitution

Prior to reconstitution, allow lyophilized powder and manufacturer-supplied diluent to warm to room temperature.¹

Reconstitute lyophilized powder with diluent provided by manufacturer.¹ Use strict aseptic technique since drug contains no preservative.¹

Reconstitute appropriate number of vials based on the indicated dosage.^{1 6} Vials contain approximately 500 or 1000 IU protein C (human); actual potency is labeled on each vial.¹

Reconstitute single-use vials of lyophilized powder by adding 5 or 10 mL of sterile water for injection to vial containing approximately 500 or 1000 units of protein C (human), respectively, using transfer needle provided by manufacturer; resulting solution contains approximately 100 units of protein C (human) per mL.^{1 6} Swirl vial gently until powder is completely dissolved.¹

Withdraw reconstituted solution from vial(s) using filter needle provided by manufacturer.¹ Before administration, replace filter needle with a suitable needle or infusion set with winged adapter.^{1 6} Filter needle provided by manufacturer is intended to filter contents of a single vial.¹

Administer at room temperature within 3 hours of reconstitution.¹

Rate of Administration

Patients weighing <10 kg: Inject at a maximum rate of 0.2 mL/kg per minute.¹

Patients weighing ≥10 kg: Inject at a maximum rate of 2 mL/minute.¹

Dosage

Potency of protein C (human) is determined by chromogenic assay and is expressed in international units (IU, units) as tested against the activity of the WHO reference standard.¹

One unit is approximately equivalent to the protein C activity (as measured by an amidolytic assay) present in 1 mL of plasma.^{1 3} The number of units of protein C is indicated on the label of each vial.¹

Pediatric Patients

Congenital Protein C Deficiency

Treatment of Acute Episodes of Venous Thrombosis and Purpura Fulminans

IV

Initially, 100–120 units/kg, followed by 60–80 units/kg every 6 hours for 3 doses and a subsequent maintenance dosage of 45–60 units/kg every 6 or 12 hours.¹

Adjust dosage according to measured plasma protein C activity; initially maintain peak plasma protein C activity at 100% of normal.¹ Following resolution of the acute event, maintain trough plasma protein C activity at a level above 25% of normal for the duration of treatment.¹

In patients initiating oral anticoagulant therapy, continue protein C replacement therapy until adequate anticoagulation is achieved.¹ (See Specific Drugs under Interactions.)

Prophylaxis of Thrombotic Events

IV

Short-term prophylaxis: Initially, 100–120 units/kg, followed by 60–80 units/kg every 6 hours for 3 doses and a subsequent maintenance dosage of 45–60 units/kg every 6 or 12 hours.¹

Long-term prophylaxis (maintenance dosage): 45–60 units/kg every 12 hours; adjust dosage to maintain trough plasma protein C activity above 25% of normal.¹ An increase in peak plasma protein C activity may be appropriate during periods of increased thrombotic risk (e.g., infection, trauma, surgery).¹

Adjust dosage according to measured plasma protein C activity; initially maintain peak plasma protein C activity at 100% of normal.¹ Following resolution of the acute event, maintain trough plasma protein C activity at a level above 25% of normal for the duration of treatment.¹

In patients initiating oral anticoagulant therapy, continue protein C replacement therapy until adequate anticoagulation is achieved.¹ (See Specific Drugs under Interactions.)

Adults

Congenital Protein C Deficiency

Treatment of Acute Episodes of Venous Thrombosis and Purpura Fulminans

IV

Initially, 100–120 units/kg, followed by 60–80 units/kg every 6 hours for 3 doses and a subsequent maintenance dosage of 45–60 units/kg every 6 or 12 hours.¹

Adjust dosage according to measured plasma protein C activity; initially maintain peak plasma protein C activity at 100% of normal.¹ Following resolution of the acute event, maintain trough plasma protein C activity at a level above 25% of normal for the duration of treatment.¹

In patients initiating oral anticoagulant therapy, continue protein C replacement therapy until adequate anticoagulation is achieved.¹ (See Specific Drugs under Interactions.)

Prophylaxis of Thrombotic Events

IV

Short-term prophylaxis: Initially, 100–120 units/kg, followed by 60–80 units/kg every 6 hours for 3 doses and a subsequent maintenance dosage of 45–60 units/kg every 6 or 12 hours.¹

Long-term prophylaxis (maintenance dosage): 45–60 units/kg every 12 hours; adjust dosage to maintain trough plasma protein C activity above 25% of normal.¹ An increase in peak plasma protein C activity may be appropriate during periods of increased thrombotic risk (e.g., infection, trauma, surgery).¹

Adjust dosage according to measured plasma protein C activity; initially maintain peak plasma protein C activity at 100% of normal.¹ Following resolution of the acute event, maintain trough plasma protein C activity at a level above 25% of normal for the duration of treatment.¹

In patients initiating oral anticoagulant therapy, continue protein C replacement therapy until adequate anticoagulation is achieved.¹ (See Specific Drugs under Interactions.)

Prescribing Limits

Pediatric Patients

Congenital Protein C Deficiency

IV

Patients weighing <10 kg: Inject at a maximum rate of 0.2 mL/kg per minute.¹

Patients weighing ≥10 kg: Inject at a maximum rate of 2 mL/minute.¹

Adults

Congenital Protein C Deficiency

IV

Inject at a maximum rate of 2 mL/minute.¹

Special Populations

No special population dosage recommendations at this time.¹

Related/similar drugs

protein c, Ceprotin

Cautions for Protein C Concentrate

Contraindications

• No known contraindications.¹

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reaction

Possible hypersensitivity reactions, including anaphylaxis.¹ If hypersensitivity reaction occurs, discontinue immediately and institute appropriate therapy as indicated.¹

Possible allergic reactions to trace amounts of murine (mouse) protein and/or heparin.¹

Antibody Formation

Inhibiting antibodies to protein C (human) not observed in clinical studies; however, the potential for developing antibodies cannot be ruled out.¹

Risk of Transmissible Agents in Plasma-derived Preparations

Potential vehicle for transmission of human viruses (i.e., HIV, hepatitis A [HAV], hepatitis B [HBV], hepatitis C [HCV], parvovirus B19) and other infectious agents.¹

Improved donor screening, viral-inactivating procedures (e.g., solvent/detergent, heat treatment), and/or immunoaffinity chromatography procedures have reduced but not completely eliminated risk of pathogen transmission with plasma-derived protein C (human) preparations.¹ Some viruses (e.g., human parvovirus B19, HAV) are difficult to remove or inactivate.¹

Human parvovirus B19 infection is most serious in pregnant women (fetal infection) or immunocompromised patients.¹

Consider vaccination (against HAV and HBV infection) for patients who routinely or repeatedly receive protein C (human).¹

Theoretical possibility of transmitting causative agent of Creutzfeldt-Jakob disease (CJD).¹

Report suspected infections to the manufacturer at 866-888-2472.¹

Bleeding

Severe bleeding reported;¹ may be associated with concomitant use of anticoagulants.¹ (See Specific Drugs under Interactions.)

Heparin-induced Thrombocytopenia

Possible heparin-induced thrombocytopenia (HIT) due to trace amounts of heparin contained in protein C (human) preparations.¹

If HIT occurs, immediately determine platelet count and consider discontinuance of protein C (human).^{1 6}

Sodium Content

The quantity of sodium in the maximum daily dosage of protein C (human) exceeds 200 mg.¹

Specific Populations

Pregnancy

Category C.¹

Lactation

Not known whether protein C (human) is distributed into milk in humans.¹

Pediatric Use

Safety and efficacy established in children ≥2 days of age.^{1 6}

Pharmacokinetics not established in pediatric patients.¹ However, systemic exposure may be reduced in very young children compared with older individuals; consider this fact when selecting a dosage regimen for children.¹ (See Pediatric Patients under Dosage and Administration and see Special Populations under Pharmacokinetics.)

Geriatric Use

Experience in patients ≥65 years of age is insufficient to determine whether they respond differently than younger adults.¹

Hepatic Impairment

Safety and efficacy not established in patients with hepatic impairment.¹

Renal Impairment

Safety and efficacy not established in patients with renal impairment.¹

Monitor closely for sodium overload.^{1 6} (See Sodium Content under Cautions.)

Common Adverse Effects

Hypersensitivity reactions (e.g., itching, rash), lightheadedness.¹

Drug Interactions

No formal drug interaction studies performed to date.^{1 6}

Specific Drugs

Protein C Concentrate Pharmacokinetics

Absorption

Plasma Concentrations

Peak plasma concentrations appear to increase dose-linearly.¹

The magnitude of increase in plasma protein C concentrations may be reduced with acute thrombosis.¹

Elimination

Half-life

9.8 hours (range: 4.9–14.7 hours) based on the noncompartmental method.¹

Half-life may be shortened in patients with acute thrombosis, purpura fulminans, or skin necrosis.¹

Special Populations

Systemic exposure may be reduced in very young children compared with older individuals because the protein may have a shorter half-life, a larger volume of distribution, and/or more rapid clearance; consider this fact when selecting a dosage regimen for children.¹ (See Dosage and Administration: Dosage.)

Stability

Storage

Parenteral

Powder for Injection

2–8°C in the original container; protect from light and avoid freezing.¹ Stable for 3 years from the date of manufacture when stored under recommended conditions; do not use beyond the expiration date on the container.^{1 6}

Actions

• An inactive precursor to a vitamin K-dependent anticoagulant serine protease, activated protein C (APC).^{1 4} Protein C is converted to APC by the thrombin/thrombomodulin complex on the endothelial cell surface.^{1 4}

• APC, in conjunction with its cofactor, protein S, generally inhibits coagulation by inactivating activated coagulation factors V (V_a) and VIII (VIII_a), which results in inhibition of the conversion of prothrombin to thrombin.^{1 4} In addition, APC facilitates fibrinolysis.¹

• In individuals with severe protein C deficiency, disruption of the protein C anticoagulant pathway results in impaired regulation of thrombin generation and associated thrombophilia.¹

Advice to Patients

• Importance of providing a copy of manufacturer’s patient information to patient and/or caregiver.^{1 5 6}

• Importance of instructing patient and/or caregiver regarding proper dosage, preparation, and administration of protein C (human), including the use of aseptic technique and safe disposal of needles and syringes if to be self-administered in the patient’s home by the patient and/or caregiver.^{1 5 6} (See IV Administration under Dosage and Administration.)

• Risk of hypersensitivity reactions.^{1 5} Importance of discontinuing therapy and immediately informing clinician if hives, urticaria, chest tightness, wheezing, hypotension, or other manifestations of hypersensitivity reaction or anaphylaxis occur.^{1 5 6}

• Risk of transmission of parvovirus B19 and/or hepatitis A from plasma-derived protein C.¹ Importance of informing clinician if symptoms of parvovirus B19 infection (e.g., fever, drowsiness, chills, runny nose, rash, joint pain) or hepatitis A infection (e.g., low grade fever, anorexia, nausea, vomiting, fatigue, jaundice, dark urine, abdominal pain) occur.¹

• Importance of patient informing clinician if they are on a low-sodium diet.¹ (See Sodium Content under Cautions.)

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

• Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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