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Protein C Concentrate (Human)

Medically reviewed by Drugs.com. Last updated on Jun 4, 2020.

Pronunciation

(PROE teen cee KON suhn trate HYU man)

Index Terms

  • Protein C

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous [preservative free]:

Ceprotin: 500 units (1 ea); 1000 units (1 ea) [contains albumin human, heparin, mouse (murine) and/or hamster protein]

Brand Names: U.S.

  • Ceprotin

Pharmacologic Category

  • Blood Product Derivative
  • Enzyme
  • Protein C

Pharmacology

Converted to activated protein C (APC). APC is a serine protease which inactivates factors Va and VIIIa, limiting thrombotic formation. In vitro data also suggest inhibition of plasminogen activator inhibitor-1 (PAF-1) resulting in profibrinolytic activity, inhibition of macrophage production of tumor necrosis factor, blocking of leukocyte adhesion, and limitation of thrombin-induced inflammatory responses.

Distribution

Vd: Median: 0.074L/kg (range: 0.044 to 0.165 L/kg)

Metabolism

Activated protein C (APC) inactivated by plasma protease inhibitors

Onset of Action

30 minutes

Time to Peak

Plasma: Tmax: 0.5 hours; range: 0.17 to 1.33 hours

Half-Life Elimination

Median: 9.8 hours; range: 4.9 to 14.7 hours

Use: Labeled Indications

Severe congenital protein C deficiency: Prevention and treatment of venous thrombosis and purpura fulminans in adults and pediatric patients with severe congenital protein C deficiency.

Contraindications

There are no contraindications listed in the manufacturer’s labeling.

Dosing: Adult

Patient variables (including age, clinical condition, severity of protein C deficiency, and plasma levels of protein C) will influence dosing and duration of therapy. Individualize frequency, duration, and dose based on protein C activity and patient pharmacokinetic profile.

Severe congenital protein C deficiency: IV:

Acute episode/short-term prophylaxis: Initial dose: 100 to 120 units/kg (for determination of recovery and half-life)

Subsequent 3 doses: 60 to 80 units/kg every 6 hours (adjust to maintain peak protein C activity of 100%)

Maintenance dose: 45 to 60 units/kg every 6 or 12 hours (adjust to maintain recommended maintenance trough protein C activity levels >25%)

Long-term prophylaxis: Maintenance dose: 45 to 60 units/kg every 12 hours (recommended maintenance trough protein C activity levels >25%)

Note: Maintain target peak protein C activity of 100% during acute episodes and short-term prophylaxis. After resolution of the acute episode or for long-term prophylaxis, maintain trough levels of protein C activity >25%. Higher peak levels of protein C may be necessary in prophylactic therapy of patients at increased risk for thrombosis (eg, infection, trauma, surgical intervention). If a patient is switched to an oral anticoagulant, continue protein C replacement until stable anticoagulation is obtained. Initiate the oral anticoagulant at a low dose and adjust incrementally, rather than using a standard loading dose.

Dosing: Pediatric

Note: Patient variables (including age, clinical condition, and plasma levels of protein C) will influence dosing and duration of therapy. Individualize dosing based on protein C activity and patient's pharmacokinetic profile.

Severe congenital protein C deficiency: Infants, Children, and Adolescents:

Acute episode/short-term prophylaxis:

Initial dose: IV: 100 to 120 units/kg/dose (for determination of recovery and half-life) followed by subsequent 3 doses: 60 to 80 units/kg/dose every 6 hours adjusted to maintain peak protein C activity of 100%.

Maintenance dose: IV: 45 to 60 units/kg/dose every 6 or 12 hours adjusted to maintain recommended maintenance trough protein C activity levels >25%. Continue until desired anticoagulation achieved.

Long-term prophylaxis: Maintenance dose: IV: 45 to 60 units/kg/dose every 12 hours (recommended maintenance trough protein C activity levels >25%).

Note: Maintain target peak protein C activity of 100% during acute episodes and short-term prophylaxis. Maintain trough levels of protein C activity >25%. Higher peak levels of protein C may be necessary in prophylactic therapy of patients at increased risk for thrombosis (eg, infection, trauma, surgical intervention).

Purpura fulminans secondary to meningococcemia: Limited data available; optimal dose not established; role in management is not defined (Fuhrman 2017):

Infants, Children, and Adolescents: IV: 100 to 150 units/kg/dose every 6 hours for 72 hours, followed by 50 to 150 units/kg/dose every 12 hours (de Kleijn 2003; Fourier 2003). Other protocols have reported a daily dose of 100 units/kg/day with doses divided every 4 to 6 hours or as a continuous infusion (Veldman 2010) and others used a loading dose (100 units/kg/dose) followed by a continuous infusion (initial rate: 10 units/kg/hour) with titration of rate based upon protein C levels (target: 80 to 120 units/mL) (White 2000). Duration of therapy variable (1 to 24 days) (Veldman 2010); activated protein C levels and clinical response should be closely monitored.

Dosing based on placebo-controlled trials and retrospective reviews. In a phase II, double-blind, placebo-controlled, dose-finding study of 40 pediatric patients (median age: 2.3 years [range: 2.4 months to 16.1 years]), a dose of 100 to 150 units/kg/dose every 6 hours for 72 hours followed by 50 to 150 units/kg/dose every 12 hours until target symptom/sign resolution or treatment duration reaches 7 days was used; results showed dose-related increases in plasma activated protein C and resolution of coagulation imbalances (de Kleijn 2003). A retrospective review of 94 pediatric patients (newborn to 18 years) reported a median dose of 100 units/kg/day divided every 4 to 6 hours (daily dose range: 28 to 375 units/kg/day) in the majority of patients (78 of the 94 patients); the remaining patients received an initial bolus with the remainder of daily dose administered as a continuous IV infusion (dosing specifics were not provided); median treatment duration of 33 hours (range: 1 to 645 hours) (Veldman 2010). An open-label, prospective study of 36 patients (3 months to 72 years) reported an initial dose of 100 units/kg followed by a continuous IV infusion with an initial rate of 10 units/kg/hour adjusted daily to maintain plasma protein C concentration 80 to 120 units/mL (White 2000).

Reconstitution

Allow vials of powder and diluent to reach room temperature. Reconstitute 500 units vial with 5 mL and 1000 units vial with 10 mL sterile water for injection (resultant concentration; 100 units/mL). Gently swirl; ensure powder is completely dissolved. Use provided filter needle to withdraw solution from vial; remove filter needle prior to administration.

Administration

IV: Administer by intravenous injection at a rate not to exceed 2 mL/minute. In infants and children <10 kg, administration should not exceed a rate of 0.2 mL/kg/minute. Administration must be completed within 3 hours of solution preparation.

Dietary Considerations

At maximum daily doses, product formulation contains sodium >200 mg.

Storage

Store under refrigeration at 2°C to 8°C (36°F to 46°F); do not freeze. Protect from light. Administer within 3 hours of reconstitution and discard any unused portion.

Drug Interactions

Acalabrutinib: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Alemtuzumab: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Apixaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of apixaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination

Bromperidol: May enhance the adverse/toxic effect of Anticoagulants. Monitor therapy

Caplacizumab: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Collagenase (Systemic): Anticoagulants may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy

Dabigatran Etexilate: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of dabigatran etexilate with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination

Dasatinib: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Deferasirox: Anticoagulants may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy

Deoxycholic Acid: Anticoagulants may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Monitor therapy

Desirudin: Anticoagulants may enhance the anticoagulant effect of Desirudin. Management: Discontinue treatment with other anticoagulants prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Consider therapy modification

Edoxaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of edoxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Management: Some limited combined use may be indicated during periods of transition from one anticoagulant to another. See the full edoxaban drug monograph for specific recommendations on switching anticoagulant treatment. Avoid combination

Estrogen Derivatives: May diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of estrogens against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Exceptions: Tibolone. Consider therapy modification

Fat Emulsion (Fish Oil Based): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Hemin: May enhance the anticoagulant effect of Anticoagulants. Avoid combination

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Management: Avoid such combinations when possible. If used concomitantly, increase diligence in monitoring for adverse effects (eg, bleeding, bruising, altered mental status due to CNS bleeds). Consider therapy modification

Ibritumomab Tiuxetan: Anticoagulants may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to an increased risk of bleeding. Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Anticoagulants. Monitor therapy

Inotersen: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Limaprost: May enhance the adverse/toxic effect of Anticoagulants. The risk for bleeding may be increased. Monitor therapy

Mesoglycan: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

MiFEPRIStone: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of bleeding may be increased. Avoid combination

Nintedanib: Anticoagulants may enhance the adverse/toxic effect of Nintedanib. Specifically, the risk for bleeding may be increased. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Topical): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Obinutuzumab: Anticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Monitor therapy

Omacetaxine: Anticoagulants may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of anticoagulants with omacetaxine in patients with a platelet count of less than 50,000/uL. Avoid combination

Omega-3 Fatty Acids: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Pentosan Polysulfate Sodium: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Progestins: May diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of progestins against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Consider therapy modification

Prostacyclin Analogues: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination. Monitor therapy

Rivaroxaban: Anticoagulants may enhance the anticoagulant effect of Rivaroxaban. Refer to separate drug interaction content and to full drug monograph content regarding use of rivaroxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination

Salicylates: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Sugammadex: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Sulodexide: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Thrombolytic Agents: May enhance the anticoagulant effect of Anticoagulants. Management: See full drug monograph for guidelines for the use of alteplase for acute ischemic stroke during treatment with oral anticoagulants. Monitor therapy

Tibolone: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Tipranavir: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Urokinase: May enhance the anticoagulant effect of Anticoagulants. Avoid combination

Vitamin E (Systemic): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Anticoagulants may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Vorapaxar: May enhance the adverse/toxic effect of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding. Avoid combination

Zanubrutinib: May enhance the adverse/toxic effect of Anticoagulants. Monitor therapy

Adverse Reactions

Frequency not defined:

Hematologic & oncologic: Major hemorrhage

Hypersensitivity: Hypersensitivity reaction

<1%, postmarketing, and/or case reports: Diaphoresis, injection site reaction, restlessness

Warnings/Precautions

Concerns related to adverse effects:

• Heparin-induced thrombocytopenia (HIT): Trace amounts of heparin contained within the formulation may lead to HIT; evaluate platelet counts if HIT is suspected.

• Hypersensitivity reactions: May contain trace amounts of mouse protein and/or heparin. Discontinue use in the presence of hypersensitivity/allergic reactions.

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment; monitor patients closely for sodium overload.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Sodium-restricted patients: Use with caution in patients where sodium restriction is necessary.

Dosage form specific issues:

• Human plasma: Product of human plasma; may potentially contain infectious agents which could transmit disease; screening of donors, as well as testing and/or inactivation or removal of certain viruses, reduces this risk. Infections thought to be transmitted by this product should be reported to the manufacturer.

Monitoring Parameters

Protein C activity (chromogenic assay) prior to and during therapy; signs and symptoms of bleeding; hemoglobin/hematocrit, PT/INR, platelet count; signs and symptoms of sodium overload in patients with renal impairment.

Pregnancy Considerations

Protein C Concentrate is derived from purified human plasma.

Patient Education

What is this drug used for?

• It is used to treat protein C deficiency.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Shortness of breath

• Dizziness

• Passing out

• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding.

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.