CurrentViva HealthPolicy IC-0168

Cinryze (C1 Esterase Inhibitor, Human) (Intravenous) — Coverage Criteria

Policy governing prior authorization, coverage criteria, dosing, and coding for Cinryze intravenous prophylaxis for hereditary angioedema (HAE) for Viva Health members. Affects prescribers, specialty providers, and billing staff seeking coverage for Cinryze.

Policy Summary

PayerViva Health

PolicyCinryze (C1 Esterase Inhibitor, Human) (Intravenous) — Coverage Criteria

Policy CodePolicy IC-0168

Change TypeNo material change

Effective Date

Next Review DateAug 5, 2025

Key ActionObtain prior authorization for Cinryze; approvals (initial and renewal) are provided for 12 months with a maximum of 2,000 billable units per 30 days.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

12 monthsprior auth length

2,000max units /30d

J0598HCPCS

D84.1diagnosis

>=6 yrmin age

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Initial Therapy — Covered when ALL of the following are met

Covered when ALL of the following are met

ALL of the following

Age: Patient is at least 6 years of age>= 6 years
Prescriber: Prescribed by or in consultation with a specialist in allergy, immunology, hematology, pulmonology, or medical genetics
No concurrent C1-targeted prophylaxis: Will not be used in combination with other prophylactic therapies targeting C1 inhibitor, activated Factor XII, or kallikrein
Examples listed: Haegarda, Andembry, Takhzyro, Orladeyo
Trigger avoidance: Confirmation patient is avoiding estrogen-containing OCPs/HRT, ACE inhibitors/ARBs, DPP-IV inhibitors, and neprilysin inhibitors
Indication-specific presentation
- Short-term prophylaxis before procedure: Receiving short-term HAE prophylaxis prior to a dental or medical procedure
- Long-term prophylaxis: Requires long-term prophylaxis based on disease activity, quality of life, resource availability, or failure of adequate on-demand therapy (e.g., Kalbitor, Firazyr, Ruconest, Berinert)
HAE subtype confirmation
- HAE Type I: Low C1-INH antigenic level, low C4, low C1-INH functional; plus family history or exclusion of acquired angioedema
- HAE Type II: Normal/elevated C1-INH antigenic with low C4 and low functional C1-INH
- HAE with normal C1-INH: Not routinely recommended; requires inadequate response/intolerance to antifibrinolytics and/or androgens and response to acute-attack agent
  Evaluated case-by-case

Continuation/Renewal — Coverage can be renewed when ALL of the following are met

Coverage can be renewed when ALL of the following are met

ALL of the following

Ongoing criteria: Patient continues to meet the universal and indication-specific criteria from initial approval
Tolerability: Absence of unacceptable toxicity (e.g., severe hypersensitivity, serious thromboembolic events)
Clinical benefit or need: Significant improvement in severity/frequency/duration of attacks achieved and sustained OR requires dose titration due to inadequate response (>1.0 HAE attack/month)> 1.0 HAE attack/month for inadequate response

Prophylaxis for HAE with normal C1‑INH (formerly HAE III) is not routinely recommended and will be evaluated on a case‑by‑case basis. For consideration of long‑term prophylaxis, the policy requires documentation that the patient had an inadequate response or intolerance to an adequate trial of prophylactic antifibrinolytic therapy (for example, tranexamic acid or aminocaproic acid) and/or a 17α‑alkylated androgen (e.g., danazol), unless such agents are contraindicated. Female patients may derive additional benefit from progestins. In addition, the patient must have demonstrated a response to an agent indicated for treatment of acute HAE attacks (for example, C1 esterase inhibitor, icatibant, or ecallantide) before long‑term prophylaxis is approved.

Use of this C1 esterase inhibitor prophylaxis in combination with other prophylactic therapies that target the C1 inhibitor pathway, activated Factor XII, or kallikrein is not allowed. Examples include prophylactic C1‑targeted products (e.g., Haegarda), Factor XII agents (e.g., Andembry), and kallikrein inhibitors (e.g., Takhzyro, Orladeyo); concurrent use may result in claim denial.

Provider and Documentation Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for initial and renewal approvals. Initial and renewal authorizations are provided for up to 12 months.

Initial authorization: up to 12 months
Renewal authorization: may be renewed every 12 months

Billing Rule

Quantity Limit

Max 2,000 billable units per 30 days. Quantity limits apply to dosing and aggregate units billed within each 30-day period.

Maximum: 2,000 billable units per 30 days

Documentation Required

Diagnostic Laboratory Documentation Required

Diagnostic laboratory confirmation of HAE subtype is required prior to authorization. Repeat blood testing is required to confirm subtype; treatment for an acute attack should not be delayed for confirmatory testing.

HAE I (C1-INH deficiency): Low C1-INH antigenic level AND low C4 level AND low C1-INH functional level (family history or exclusion of acquired angioedema supportive)
HAE II (C1-INH dysfunction): Normal/elevated C1-INH antigenic level AND low C4 level AND low C1-INH functional level
HAE with normal C1-INH: diagnosis based on clinical criteria and prior trial of antifibrinolytic/androgen therapy (see step therapy)

Step Therapy

Step Therapy for HAE with Normal C1‑INH

For HAE with normal C1‑INH, step therapy is required before consideration of long-term prophylaxis.

Patient must have had an inadequate response or intolerance to an adequate trial of an antifibrinolytic agent (e.g., tranexamic acid or aminocaproic acid) and/or a 17α-alkylated androgen (e.g., danazol) unless contraindicated
Female patients may derive additional benefit from progestins; documentation of trials and contraindications must be provided
Patient should demonstrate response to an agent indicated for acute attacks (e.g., C1 esterase inhibitor, icatibant, ecallantide) prior to long-term prophylaxis

Documentation Required

Specialist Consult and Trigger Avoidance

Specialist involvement and counseling on trigger avoidance are required.

Must be prescribed by, or in consultation with, a specialist in allergy, immunology, hematology, pulmonology, or medical genetics
Provider must confirm counseling and steps to avoid known HAE attack triggers, including avoidance of estrogen-containing oral contraceptives and hormone replacement therapy, ACE inhibitors or ARBs, DPP‑IV inhibitors (e.g., sitagliptin), and neprilysin inhibitors (e.g., sacubitril)

Denial Risk

Concurrent Prophylactic Therapy Prohibition

Concurrent use with other prophylactic therapies targeting the C1 inhibitor pathway, activated Factor XII, or kallikrein is prohibited.

Do not use concurrently with other prophylactic therapies targeting C1 inhibitor (e.g., Haegarda), activated Factor XII (e.g., Andembry), or kallikrein (e.g., Takhzyro, Orladeyo)

HAE Subtype Definitions

HAE Type I

Defining laboratory criteriaLow C1‑INH antigenic level (below lab lower limit of normal)

Complement markerLow C4 level (below lab lower limit of normal)

Functional assayLow C1‑INH functional level (below lab lower limit of normal)

Supporting clinical evidenceFamily history of HAE or exclusion of acquired angioedema (e.g., symptom onset <30 years, normal C1q, no underlying lymphoproliferative disorder)

HAE Type II

C1‑INH antigenic levelNormal to elevated C1‑INH antigenic level

Complement markerLow C4 level (below lab lower limit of normal)

Functional assayLow C1‑INH functional level (below lab lower limit of normal)

HAE with normal C1‑INH

C1‑INH levelsNormal C1‑INH antigenic and functional levels

Prophylaxis stanceLong‑term prophylaxis is not routinely recommended and will be evaluated case‑by‑case

Required prior therapiesMust demonstrate inadequate response or intolerance to adequate trial of antifibrinolytics (e.g., tranexamic acid) and/or 17α‑alkylated androgens unless contraindicated

Acute‑attack responseDocumentation of response to an agent for acute HAE attacks (e.g., C1 esterase inhibitor, icatibant, ecallantide) required before considering long‑term prophylaxis

Background

Hereditary angioedema (HAE) is a complement‑pathway disorder characterized by episodic, potentially severe angioedema due to deficiency or dysfunction of the C1 esterase inhibitor (C1‑INH). Clinical presentations include attacks requiring short‑term prophylaxis for procedures and patients who may need long‑term prophylaxis when disease activity, quality of life impact, resource availability, or failure of adequate on‑demand therapy justify it. HAE is classified by laboratory findings into types associated with low C1‑INH antigenic and functional levels (Type I), dysfunctional C1‑INH with low functional levels (Type II), and presentations with normal C1‑INH levels (HAE with normal C1‑INH), the latter of which requires individualized evaluation before considering routine prophylaxis.

42227-0081-xx	Cinryze 500 international units (IU) single-dose vial
42227-0083-xx	Cinryze 500 IU single-dose carton kit (containing a single-dose vial of Cinryze and a 5 mL vial of Sterile Water for Injection)

OpenPayer

Cinryze (C1 Esterase Inhibitor, Human) (Intravenous) — Coverage Criteria

Coverage Criteria for Cinryze (C1 Esterase Inhibitor, Human)

Provider and Documentation Requirements

Coding and Billing Codes

HAE Subtype Definitions

Background