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Protein C Concentrate (Human)

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

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: Infants, Children, and Adolescents: IV: Refer to adult dosing.

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: Renal Impairment

There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); monitor closely for sodium overload.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

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

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

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): 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 Lexi-Drugs full drug monograph content regarding use of apixaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination

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 Lexi-Drugs 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. Consider therapy modification

Edoxaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to Lexi-Drugs 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

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. Consider therapy modification

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

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

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

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

Nonsteroidal Anti-Inflammatory Agents: 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 Lexi-Drugs 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

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

Tositumomab and Iodine I 131 Tositumomab: Anticoagulants may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse effects may be increased. Monitor therapy

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

Vitamin E: May enhance the anticoagulant effect of Anticoagulants. Vitamin E may also increase the overall risk for bleeding. Monitor therapy

Vitamin E (Oral): 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

Adverse Reactions

As with all drugs which may affect hemostasis, bleeding may be associated with protein C administration. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the concurrent use of multiple agents that alter hemostasis and patient susceptibility. Frequency not defined.

Central nervous system: Lightheadedness

Hematologic: Bleeding

Miscellaneous: Hypersensitivity reactions (itching and rash)

Postmarketing and/or case reports: Fever, hemothorax, hypotension, hyperhidrosis, 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 Risk Factor

C

Pregnancy Considerations

Animal reproductive studies have not been conducted.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber severe dizziness, syncope, ecchymosis, or hemorrhaging (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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