CurrentCignaPolicy IP0342

Hematology - Ceprotin

Cigna coverage policy for intravenous human protein C concentrate (Ceprotin) for the prevention and treatment of venous thrombosis and purpura fulminans in patients with severe congenital protein C deficiency; applies to Cigna-administered health benefit plans and providers seeking coverage decisions.

Policy Summary

PayerCigna

PolicyHematology - Ceprotin

Policy CodePolicy IP0342

Change TypeTitle update and dosing info added (non-material)

Effective Date3/15/2025

Next Review Date

Key ActionSubmit prior authorization with documentation confirming severe congenital protein C deficiency and supporting dosing to approve up to 4,440 IU/kg per 28 days.

SourceLink

POLICY UPDATE CHANGES

Updated coverage policy title; no criteria change.

Added dosing information.

4,440 IU/kgmaximum approval dosing per 28 days

Initial up to 12 moauthorization duration

Reauth up to 12 moreauthorization duration

J2724listed HCPCS code

Coverage Criteria for Ceprotin (protein C concentrate)

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Initial Therapy

Covered when ALL of the following are met:

Protein C Deficiency, Severe - Diagnostic confirmation: Documented diagnosis of protein C deficiency is confirmed by ONE of: (i) plasma protein C activity below the lower limit of normal based on age-specific reference range for the reporting laboratory; (ii) plasma protein C antigen below the lower limit of normal based on age-specific reference range for the reporting laboratory; (iii) genetic testing demonstrating biallelic pathogenic variants in the PROC gene.one of i-iii required

Exclusion of acquired causes: Acquired causes of protein C deficiency have been excluded (for example, recent use of vitamin K antagonists within 30 days, vitamin K deficiency, chronic liver disease, recent thrombosis, recent surgery, or disseminated intravascular coagulation).

Clinical history: Current or prior history of symptoms associated with severe protein C deficiency (for example, purpura fulminans, thromboembolism).

Prescribing provider: Medication is prescribed by or in consultation with a hematologist.

Dosing: approve up to 4,440 IU/kg intravenously per 28 days.

Reauthorization / Continuation Therapy

Reauthorization covered when ALL of the following are met:

Continuation criteria: Above medical necessity criteria are met AND there is documentation of beneficial response.

Use of protein C concentrate (Ceprotin) for any indication other than treatment or prevention of venous thrombosis and purpura fulminans in patients with severe congenital protein C deficiency is considered experimental, investigational, or unproven and is not covered.

Coding, Dosing Limits, and Key Dosing Parameters

Considered Medically Necessary when criteria metHCPCSCovered

J2724

Injection, protein C concentrate, intravenous, human, 10 IU

inv-05: Maximum per 28 days — numeric dosing limit

Maximum allowed per 28 days4,440 IU/kg per 28 days (allows for prophylactic dosing plus three days of acute/ perioperative management)

Review for excess dosingDoses exceeding 4,440 IU/kg per 28 days will be reviewed case-by-case by a clinician

Basis for limitLimit set to accommodate prophylaxis plus three days of acute episodes or perioperative management per MASAC-based considerations

inv-06: Maintenance prophylactic dose — long-term prophylaxis dosing range

Maintenance prophylactic dose (long-term)45 to 60 IU/kg once every 12 hours by intravenous infusion

PurposeFor long-term prophylaxis in severe congenital protein C deficiency

Home supply recommendationPatients on prophylaxis should have additional doses available for breakthrough episodes per MASAC guidance

inv-07: Initial acute episode dosing — initial and subsequent dosing schedule and maintenance

Initial dose for acute episode100 to 120 IU/kg intravenous initial dose

Subsequent acute dosingSubsequent three doses: 60 to 80 IU/kg once every 6 hours by intravenous infusion

Post-acute maintenanceMaintenance thereafter: 45 to 60 IU/kg once every 6 to 12 hours by intravenous infusion

Prior Authorization, Documentation, and Provider Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Ceprotin. Initial and reauthorization approvals may be granted for up to 12 months per authorization. Dosing approvals follow policy limits (approve up to 4,440 IU/kg IV per 28 days). Receipt of sample product does not satisfy prior authorization or documentation requirements.

Prior authorization required
Initial and reauthorization approval: up to 12 months
Dose limit: up to 4,440 IU/kg IV per 28 days

Step Therapy

No step therapy requirements are specified for Ceprotin in this policy.

Documentation Required

Required Documentation for Medical Necessity

Documentation must support the diagnosis of severe congenital protein C deficiency and exclusion of acquired causes. Required documentation includes laboratory or genetic confirmation and clinical history; medication must be prescribed by or in consultation with a hematologist.

Documentation of ONE of: plasma protein C activity below lab-specific lower limit of normal; plasma protein C antigen below lab-specific lower limit of normal; genetic testing showing biallelic pathogenic PROC variants
Documentation that acquired causes of protein C deficiency have been excluded (examples: recent vitamin K antagonist use within 30 days, vitamin K deficiency, chronic liver disease, recent thrombosis, recent surgery, DIC)
Documentation of current or prior symptoms consistent with severe protein C deficiency (e.g., purpura fulminans, thromboembolism)
Prescriber is a hematologist or treatment is in consultation with a hematologist
Receipt of sample product does not satisfy documentation requirements

Denial Risk

Non‑Covered Indications

Use of Ceprotin for any indication other than severe congenital protein C deficiency (as defined by the policy criteria) is considered experimental, investigational, or unproven and is not covered.

Not covered: indications other than severe congenital protein C deficiency meeting policy criteria

Definitions

inv-13: Severe congenital protein C deficiency definition — biallelic pathogenic PROC variants or very low protein C levels with clinical presentation

Genetic definitionBiallelic pathogenic variants in the PROC gene (autosomal recessive) defining severe congenital protein C deficiency

Protein C level thresholdProtein C levels by definition are < 0.01 IU/mL and are often undetectable in severe congenital deficiency

Typical clinical presentationOften presents with purpura fulminans and disseminated intravascular coagulation within 72 hours of birth; may present later with thrombosis

Need to exclude acquired causesCritical to exclude acquired causes of low protein C (e.g., vitamin K antagonists, vitamin K deficiency, chronic liver disease, severe infection, or DIC)

Background

Severe congenital protein C deficiency is an autosomal recessive disorder caused by biallelic pathogenic variants in the PROC gene that result in very low or undetectable protein C levels. It typically presents in neonates with life-threatening thrombotic manifestations such as purpura fulminans and disseminated intravascular coagulation and may also present with venous thromboembolism. Incidence is rare (approximately 1 per 4 million births).

Acquired causes of low protein C (for example, recent use of vitamin K antagonists, vitamin K deficiency, chronic liver disease, severe infection or disseminated intravascular coagulation) should be excluded when establishing the diagnosis. Confirmation is by one of: plasma protein C activity below the laboratory age‑specific lower limit, plasma protein C antigen below the laboratory age‑specific lower limit, or genetic testing demonstrating biallelic pathogenic PROC variants.