CurrentCentenePolicy HIM.PA.170

C1 Esterase Inhibitors (Berinert, Cinryze, Haegarda, Ruconest) (PDF)

Defines prior authorization clinical criteria, age limits, dosing limits, indications (acute treatment, short-term prophylaxis, long-term prophylaxis) and continuation/renewal requirements for Berinert, Cinryze, Haegarda, and Ruconest for hereditary angioedema (HAE) across Centene HIM lines of business.

Policy Summary

PayerCentene

PolicyC1 Esterase Inhibitors (Berinert, Cinryze, Haegarda, Ruconest) (PDF)

Policy CodePolicy HIM.PA.170

Change TypeStep therapy bypass addedreferences updated

Effective DateJan 1, 2024

Next Review Date

Key ActionPrior authorization required; submit documentation (office notes, labs) demonstrating the member meets all approval criteria.

SourceLink

POLICY UPDATE CHANGES

Added step therapy bypass for Illinois HIM per IL HB 5395 effective 2026-01-01.

3Q 2025 annual review: references reviewed and updated; step therapy bypass added for IL HIM.

3Q 2024 and 3Q 2025 annual reviews noted references updated; 3Q 2024 noted no significant changes.

4Products covered

≤4Acute doses permitted per month

2Short-term prophylaxis doses per procedure

12 moContinued therapy approval duration (acute)

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Coverage Summary

Defines Centene HIM prior authorization clinical criteria and coverage stance (covered_with_criteria) for C1 esterase inhibitors Berinert, Cinryze, Haegarda, and Ruconest (Policy HIM.PA.170). Policy scope includes diagnostic confirmation, age limits (Berinert: ≥ 5 years; Cinryze/Haegarda: ≥ 6 years; Ruconest: ≥ 13 years), indication-specific coverage (acute treatment, short-term prophylaxis, long-term prophylaxis), dosing limits, and continuation requirements across Centene HIM lines of business.

Acute treatment: permitted when criteria met, limited to ≤ 4 doses per month; Berinert and Ruconest supported for acute use with Ruconest not established for laryngeal attacks (Ruconest allowed only if member does not experience laryngeal attacks). Short-term prophylaxis: permitted for major dental or surgical procedures with ≤ 2 doses per procedure. Long-term prophylaxis: permitted for Cinryze or Haegarda when member has > 1 severe event/month OR is disabled > 5 days/month OR has prior airway compromise.

Dose limits (must not be exceeded): Berinert 20 IU/kg per single dose, up to 2 doses in 24 hours; Cinryze 2,000 units every 3–4 days (age-specific dosing detailed in policy); Haegarda 60 IU/kg twice weekly; Ruconest 4,200 IU per single dose, up to 2 doses in 24 hours. Continued therapy approvals require meeting initial criteria/continuity of care rules and limits (acute treatment continued approvals capped at dosing limits).

Initial Therapy Criteria — Hereditary Angioedema (HAE)

Other Diagnoses / Indications (Initial)

Continuation Therapy Criteria

Continued Therapy - Short Term Prophylaxis

Re-authorization rules

Re-authorization is not permitted; members must meet initial approval criteria

Provider Actions & Billing

Prior Authorization

Prior authorization required

Prior authorization is required for Berinert, Cinryze, Haegarda, and Ruconest. Submit supporting documentation (office chart notes, lab results, or other clinical information) showing the member meets all approval criteria.

Affected HCPCS/J‑codes: J0596, J0597, J0598, J0599

Documentation Required

Diagnostic confirmation required

Document diagnosis of HAE with a history of recurrent angioedema plus one of the following: low C4 and low C1‑INH antigenic or functional levels; OR presence of a mutation associated with HAE; OR a family history of angioedema with documented failure of high‑dose antihistamine therapy (e.g., cetirizine 40 mg/day or equivalent) for ≥1 month or an interval expected to be associated with ≥3 attacks.

Applicable Codes

HCPCS/J-codes for C1 esterase inhibitorsmixed

J0596	Injection, C-1 esterase inhibitor (recombinant), Ruconest, 10 units
J0597	Injection, C-1 esterase inhibitor (human), Berinert, 10 units
J0598	Injection, C-1 esterase inhibitor (human), Cinryze, 10 units
J0599	Injection, C-1 esterase inhibitor (human), Haegarda, 10 units

Clinical Evidence & Guidelines

Evidence and references cited in the policy include guideline sources and product prescribing information: US HAEA Medical Advisory Board 2020 Guidelines (Busse et al.) and the international WAO/EAACI 2021 guideline, plus multiple product prescribing information documents for Berinert, Cinryze, Ruconest, and Haegarda as listed in the policy references.

Background: C1 esterase inhibitors (human and recombinant) are FDA‑approved for treatment of acute HAE attacks and for prophylaxis in product‑specific populations; prescribing information for each product is referenced in the policy (Berinert, Cinryze, Ruconest, Haegarda).

Background

Background from the policy: C1 esterase inhibitors are FDA‑approved for acute HAE attacks and for prophylaxis in product‑specific age groups (Berinert: acute attacks in adults and pediatrics; Ruconest: acute attacks in adults and adolescents; Cinryze and Haegarda: routine prophylaxis in patients ≥ 6 years as specified). The policy covers medical necessity criteria, dosing limits, age limits, contraindications, alternative therapies, and references to product prescribing information and evidence‑based guidelines.

Policy scope and key elements: requires documentation of HAE diagnosis (recurrent angioedema plus low C4 and low C1‑INH antigenic or functional level or genetic mutation/family history plus failed high‑dose antihistamine), provider specialty consultation requirement, step therapy requirements for certain indications (e.g., icatibant failure for acute attacks in adults; step therapy for Cinryze long‑term prophylaxis requiring prior failure of Haegarda, Takhzyro, and Orladeyo when age‑appropriate), and explicit exclusions for combining FDA‑approved products for the same indication.

Contraindications and safety: policy references product contraindications including known or suspected allergy to rabbits for Ruconest and history of immediate/life‑threatening hypersensitivity reactions to C1‑INH products; therapeutic alternatives and dosing details (including icatibant, Orladeyo, Takhzyro, and antihistamines) are provided in appendices and prescribing information citations.

Revision History

2026-01-01policy_changeLatest

Added step therapy bypass for Illinois HIM per IL HB 5395: the step therapy requirements for icatibant (acute attacks, age ≥18) and for Cinryze long-term prophylaxis do not apply to Illinois HIM requests as of 1/1/2026.

2025-08-25annual_review

3Q 2025 annual review: references reviewed and updated; added step therapy bypass for Illinois HIM per IL HB 5395.

2024-05-08administrative_update

Policy Summary

PayerCentene

PolicyC1 Esterase Inhibitors (Berinert, Cinryze, Haegarda, Ruconest) (PDF)

Policy CodePolicy HIM.PA.170

Change TypeStep therapy bypass addedreferences updated

Effective DateJan 1, 2024

Next Review Date

Key ActionPrior authorization required; submit documentation (office notes, labs) demonstrating the member meets all approval criteria.

SourceLink

On This Page

Step Therapy

Step therapy for acute attacks (age ≥18)

For treatment of acute HAE attacks in adults (age ≥18 years), approval requires documented failure of icatibant (Firazyr) unless contraindicated or clinically significant adverse effects occur. Prior authorization may be required for icatibant. Note: Illinois HIM requests are exempt from these step therapy requirements as of 2026‑01‑01 per IL HB 5395.

Step Therapy

Step therapy for Cinryze long-term prophylaxis

For Cinryze used for long‑term prophylaxis, approval requires documented failure of Haegarda and Takhzyro, and if the member is age ≥12 years, failure of Orladeyo, unless contraindicated or significant adverse effects occur. Prior authorization may be required for these alternatives. Note: Illinois HIM requests are exempt from these step therapy requirements as of 2026‑01‑01 per IL HB 5395.

Billing Rule

Dose limits enforce billing caps

Claims are limited by per‑dose and per‑month maxima. Examples of dosing limits used to enforce billing caps include the following per policy: Berinert — 20 IU/kg per single dose, up to 2 doses in 24 hours; Cinryze — 2,000 units every 3–4 days; Haegarda — 60 IU/kg per dose twice weekly; Ruconest — 4,200 IU per single dose, up to 2 doses in 24 hours. Acute treatment requests must not exceed 4 doses per month.

Per‑dose examples: Berinert, Cinryze, Haegarda, Ruconest
Per‑month maximum for acute treatment: ≤ 4 doses/month

Denial Risk

Combination therapy exclusion

Requests will be denied if the member is using the requested product in combination with another FDA‑approved product for the same indication (e.g., combining acute agents or combining long‑term prophylaxis agents).

3Q 2024 administrative updates: annual review noted no significant clinical changes; references reviewed and updated.