CurrentViva Health PlanPolicy IC-0168

Cinryze (C1 Esterase Inhibitor, Human) for Hereditary Angioedema Prophylaxis

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This policy governs prior authorization, coverage criteria, dosing, renewal, and billing for intravenous Cinryze used to prevent hereditary angioedema attacks for Viva Health Plan commercial members and their providers.

Policy Summary

PayerViva Health Plan

PolicyCinryze (C1 Esterase Inhibitor, Human) for Hereditary Angioedema Prophylaxis

Policy CodePolicy IC-0168

Change TypeNo material change

Effective DateN/A

Last ReviewOct 1, 2026

Next Review DateN/A

Key ActionSubmit prior authorization with documentation that the member is at least 6 years old and meets the applicable hereditary angioedema prophylaxis criteria.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

6 yearsMinimum age for initial approval

12 monthsAuthorization duration

2,000 unitsMaximum allowed per 30 days

J0598HCPCS billing code

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CurrentViva Health PlanPolicy IC-0168

Cinryze (C1 Esterase Inhibitor, Human) for Hereditary Angioedema Prophylaxis

Customize your policy alerts

Sign up for vivahealthplan Policy IC-0168 alerts

Get alerted when Policy IC-0168 changes without checking for updates manually.

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Policy Summary

PayerViva Health Plan

PolicyCinryze (C1 Esterase Inhibitor, Human) for Hereditary Angioedema Prophylaxis

Policy CodePolicy IC-0168

Change TypeNo material change

Effective DateN/A

Last ReviewOct 1, 2026

Next Review DateN/A

Key ActionSubmit prior authorization with documentation that the member is at least 6 years old and meets the applicable hereditary angioedema prophylaxis criteria.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

6 yearsMinimum age for initial approval

12 monthsAuthorization duration

2,000 unitsMaximum allowed per 30 days

J0598HCPCS billing code

Coverage Criteria

Initial Therapy

Covered when ALL of the following criteria are met:

ALL of the following

Member is at least 6 years of age.>= 6 years
Cinryze is prescribed by, or in consultation with, a specialist in allergy, immunology, hematology, pulmonology, or medical genetics.
Provider confirms the member has been counseled to avoid possible medication triggers for hereditary angioedema (HAE) attacks, including estrogen-containing medications and ACE inhibitors.
Member has a history of ONE or more of the following:
- Recurrent swelling of mucous membranes, skin surface, or subcutaneous tissue.
- Recurrent abdominal attacks with severe abdominal pain, nausea, vomiting, or diarrhea.
- Episodes of upper-airway edema, including mouth, tongue, or larynx involvement.
- Prodromal signs or symptoms preceding angioedema attacks, including anxiety, nausea, paresthesia, or fatigue.
- Positive family history of HAE.
Member will receive ONE of the following HAE prophylaxis methods:
- Short-term prophylactic treatment prior to a procedure, such as a dental or medical procedure.
- Long-term prophylactic treatment based on the provider's assessment of disease activity, quality of life, availability of health care resources, and/or failure to achieve adequate control with appropriate acute HAE attack therapy.
Diagnosis of HAE is confirmed by ONE of the following:
- HAE due to C1 inhibitor deficiency (HAE-C1-INH) Type 1 or 2
  - At least one current or historical laboratory or genetic confirmation:
    C1-INH antigenic level is below the lower limit of normal as defined by the performing laboratory.
    C1-INH functional level is below the lower limit of normal as defined by the performing laboratory.
    Genetic testing confirms pathogenic mutation(s) in SERPING1.
- HAE with normal C1-INH (HAE-nC1-INH)
  - Current or historical C1-INH level is normal, including C1-INH antigenic or functional level, as defined by the performing laboratory.
  - At least one of the following:

Renewal Therapy

Covered for renewal when ALL of the following criteria are met:

ALL of the following

Member continues to meet the universal and other indication-specific relevant criteria identified in the Initial Approval Criteria section.
There is no unacceptable toxicity from Cinryze, including severe hypersensitivity reactions or serious arterial or venous thromboembolic events.
At least one of the following:
- Member has experienced clinical benefit from therapy, such as reduced attack severity and/or frequency or shortened attack duration.
- Member requires dose titration because of an inadequate response to therapy, defined as more than 1.0 HAE attack per month regardless of severity or duration.> 1.0 HAE attack/month

Cinryze will not be used in combination with another therapy indicated for prophylaxis of HAE attacks. Combination therapy with another agent is allowable when Cinryze is requested for short-term prophylaxis only.

Other causes of angioedema must be ruled out, including drug-induced angioedema, mast cell-mediated angioedema, and acquired angioedema due to C1-INH deficiency.

Coding and Dosing Requirements

Covered Diagnosis CodesICD-10Covered

D84.1

Defects in the complement system

HCPCS CodeHCPCSCovered

J0598

Injection, c-1 esterase inhibitor (human), cinryze, 10 units; 1 billable unit = 10 international units

NDC AvailabilityNDC

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

Dosing limit

Maximum quantity2,000 billable units per 30 days

Measurement period30 days

Billing basisHCPCS billable units

High-dose antihistamine trial for HAE-nC1-INH

Trial duration4 weeks

Medication classSecond-generation H1 antagonist

Required dose

Authorization and Documentation Actions

Prior Authorization

Initial Prior Authorization Required

Obtain prior authorization for Cinryze before treatment. Initial authorization is available for 12 months (365 days) when the member is at least 6 years old and all applicable universal, indication-specific, diagnostic, and dosing criteria are met.

Member is at least 6 years of age.
Cinryze is requested for prophylaxis against hereditary angioedema (HAE) attacks.
Document specialist prescribing or consultation, HAE history and diagnosis, exclusion of other causes, and the applicable HAE-C1-INH or HAE-nC1-INH evidence.
Use short-term prophylaxis before a procedure or long-term prophylaxis based on disease activity, quality of life, health care resource availability, or inadequate control with appropriate acute HAE therapy.

Prior Authorization

Annual Renewal Authorization

Renewal authorization may be granted for another 12 months (365 days) when the member continues to meet the applicable initial and universal criteria, has no unacceptable toxicity, and continues to benefit from therapy or requires dose titration because of inadequate response.

Policy Background

Cinryze is an intravenous human C1 esterase inhibitor used to prevent hereditary angioedema attacks. Coverage is available for Viva Health Plan commercial members who are at least 6 years of age and have documented hereditary angioedema, including HAE due to C1-inhibitor deficiency Type 1 or 2 and specified hereditary angioedema with normal C1 inhibitor. Prophylaxis may be requested for a procedure or for long-term prevention based on disease activity, quality of life, healthcare resource considerations, or inadequate control with appropriate acute attack therapy.

Definitions

International Unit (IU)

DefinitionOne International Unit corresponds to the amount of C1 esterase inhibitor present in 1 mL of normal plasma

Reference standardDefined by the WHO international reference standard

Historical unit conversion100 U = 83 IU; a conversion factor of 0.83 may be used

HAE-C1-INH

ConditionHereditary angioedema due to C1 inhibitor deficiency

Types includedType 1 or Type 2

Supporting evidenceLow C1-INH antigenic or functional levels, or a pathogenic SERPING1 mutation

Initial Therapy Criteria

Initial approval requires all of the following criteria.

Initial Cinryze approval

Universal criteria: Prescribed by or in consultation with a specialist in allergy, immunology, hematology, pulmonology, or medical genetics; will not be used with another HAE prophylaxis therapy except when requested for short-term prophylaxis only; and the member has been counseled to avoid possible HAE medication triggers, including estrogen-containing medications and ACE inhibitors.
Clinical history and alternative-cause exclusion: Member has recurrent mucosal, skin, or subcutaneous swelling; recurrent abdominal attacks with severe abdominal pain, nausea, vomiting, or diarrhea; upper-airway edema; prodromal symptoms preceding attacks; or a positive family history of HAE, and other causes of angioedema have been ruled out.
Prophylaxis intent: Cinryze is requested for short-term prophylaxis before a dental or medical procedure or for long-term prophylaxis based on disease activity, quality of life, availability of healthcare resources, or failure to achieve adequate control with appropriate acute HAE attack therapy.

Continuation Criteria

Continuation Therapy Criteria

Continuation approval requires continued eligibility, safety, and response.

Continuation therapy

Clinical benefit or dose-titration need: Member has experienced clinical benefit from therapy, such as reduced attack severity or frequency or shortened attack duration; or requires dose titration because of inadequate response.> 1.0 HAE attack per month, regardless of severity or duration

Step Therapy

Step	Requirement	Qualifying pathway
1	For HAE with normal C1 inhibitor, demonstrate one qualifying therapy history.	Prior beneficial response to a therapy indicated for treatment of acute HAE attacks; OR inadequate response or intolerance to an adequate trial of another prophylactic HAE therapy, such as tranexamic acid, aminocaproic acid, danazol, and/or progestin therapy specific to females.

Quantity Limits

Cinryze quantity limit

DrugCinryze

Quantity limit2,000 billable units

Time periodPer 30 days

Policy Summary

PayerViva Health Plan

PolicyCinryze (C1 Esterase Inhibitor, Human) for Hereditary Angioedema Prophylaxis

Policy CodePolicy IC-0168

Change TypeNo material change

Effective DateN/A

Last ReviewOct 1, 2026

Next Review DateN/A

Key ActionSubmit prior authorization with documentation that the member is at least 6 years old and meets the applicable hereditary angioedema prophylaxis criteria.

SourceLink

On This Page

Confirmed presence of known HAE-causing mutation(s) in F12, ANGPT1, PLG, KNG1, MYOF, KNG1, and/or HS3ST6.
ALL of the following
- Recurrent angioedema attacks without hives are refractory to a 4-week trial of high-dose antihistamines, defined as a second-generation H1 antagonist at four times the standard dose.
- Member has demonstrated ONE of the following:
  - Prior beneficial response to a therapy indicated for the treatment of acute HAE attacks.
  - Inadequate response or intolerance to an adequate trial of another prophylactic HAE therapy, such as an antifibrinolytic agent (tranexamic acid or aminocaproic acid), a 17α-alkylated androgen such as danazol, and/or progestin therapy specific to females.

Four times the standard dose

Inadequate response requiring dose titration

Attack frequency thresholdMore than 1.0 HAE attack per month

SeverityRegardless of severity

DurationRegardless of attack duration

Adult and adolescent standard dose

PopulationAdults and adolescents at least 12 years of age

Dose1,000 IU

Route and frequencyIntravenous injection every 3 to 4 days

Adult and adolescent maximum response-based dose

Maximum doseUp to 2,000 IU every 3 or 4 days

Weight limitNot exceeding 80 IU/kg

UseMay be considered for patients who have not responded adequately to initial dosing, based on individual response

Pediatric dose

PopulationPediatrics 6 to 11 years of age

Starting dose500 IU by intravenous injection every 3 to 4 days

Response-based adjustmentMay be adjusted up to 1,000 IU every 3 to 4 days

Document continued eligibility and indication-specific criteria.
Document absence of severe hypersensitivity reactions, serious arterial or venous thromboembolic events, or other unacceptable toxicity.
Clinical benefit may include reduced attack severity or frequency or shortened attack duration.
Dose titration may be considered for inadequate response, including more than 1 HAE attack per month regardless of severity or duration.

Documentation Required

HAE-nC1-INH Alternative Therapy History

For HAE with normal C1 inhibitor (HAE-nC1-INH), document that the member has demonstrated a prior beneficial response to an acute HAE therapy or an inadequate response or intolerance to an adequate trial of another prophylactic HAE therapy.

Acceptable prior prophylactic therapies include an antifibrinolytic such as tranexamic acid or aminocaproic acid, a 17-alpha-alkylated androgen such as danazol, or progestin therapy when specific to females.

Documentation Required

Specialist Prescribing and Trigger Counseling

Ensure Cinryze is prescribed by, or used in consultation with, a specialist and document counseling to avoid potential HAE medication triggers.

Acceptable specialists include allergy, immunology, hematology, pulmonology, or medical genetics.
Document counseling to avoid possible triggers such as estrogen-containing medications and ACE inhibitors.

Documentation Required

HAE Clinical and Diagnostic Documentation

Submit clinical and diagnostic records supporting HAE prophylaxis. The record must establish a qualifying attack history or family history, rule out other causes of angioedema, and identify the intended prophylaxis approach and confirmed HAE diagnosis.

Document recurrent swelling of mucous membranes, skin, or subcutaneous tissue; recurrent abdominal attacks with severe pain, nausea, vomiting, or diarrhea; upper-airway edema; prodromal symptoms; or a positive family history of HAE.
Rule out drug-induced angioedema, mast cell-mediated angioedema, and acquired angioedema due to C1-INH deficiency.
Identify short-term prophylaxis before a dental or medical procedure or long-term prophylaxis based on disease activity, quality of life, resources, or inadequate acute-therapy control.
For HAE-C1-INH, document Type 1 or Type 2 disease with low C1-INH antigenic or functional levels or pathogenic SERPING1 mutation evidence.

Documentation Required

HAE-nC1-INH Supporting Records

For HAE-nC1-INH requests, provide supporting records demonstrating normal C1-INH results and a qualifying genetic or clinical presentation.

Document a current or historical normal C1-INH antigenic or functional level as defined by the performing laboratory.
Provide confirmed pathogenic mutation evidence in F12, ANGPT1, PLG, KNG1, MYOF, or HS3ST6 when applicable.
Alternatively, document recurrent angioedema attacks without hives that are refractory to a 4-week trial of high-dose antihistamines, defined as a second-generation H1 antagonist at four times the standard dose.

Documentation Required

Renewal Response and Safety Documentation

For renewal, document ongoing eligibility, continued safety, and clinical benefit from Cinryze, or explain the need for dose titration because of inadequate response.

Confirm continued compliance with universal and indication-specific criteria.
Document no unacceptable drug toxicity, including severe hypersensitivity or serious arterial or venous thromboembolic events.
Document reduced attack severity or frequency, shorter attack duration, or another meaningful clinical benefit.
If response is inadequate, document more than 1 HAE attack per month and the rationale for dose titration.

Denial Risk

Eligibility or Diagnostic Criteria Not Met

Authorization may be denied when eligibility or diagnostic requirements are not met, including the minimum age, specialist involvement, or required clinical history and diagnosis.

Member must be at least 6 years of age.
Prescription must be by or in consultation with an allergy, immunology, hematology, pulmonology, or medical genetics specialist.
Required recurrent swelling, abdominal or airway attacks, prodromal symptoms, family history, exclusion of other causes, and confirmed HAE documentation must be present as applicable.

Denial Risk

Prohibited Prophylaxis Combination

Do not use Cinryze with another therapy indicated for prophylaxis of HAE attacks. Combination therapy is allowable only when Cinryze is requested for short-term prophylaxis.

Document the intended prophylaxis method and any exception supporting short-term use before a procedure.

Denial Risk

Insufficient HAE-nC1-INH Evidence

An HAE-nC1-INH request may be denied when the required laboratory, mutation, or clinical evidence is absent or incomplete.

Provide current or historical normal C1-INH antigenic or functional results.
Provide qualifying mutation evidence in F12, ANGPT1, PLG, KNG1, MYOF, or HS3ST6, or document recurrent angioedema without hives refractory to 4 weeks of high-dose antihistamines.
Also provide evidence of a beneficial acute-HAE-treatment response or inadequate response or intolerance to an adequate alternative prophylactic HAE therapy.

Billing Rule

Dose or Quantity Exceeds Policy Limits

Requests exceeding the policy quantity or dosing limits may be denied. Verify the requested dose, frequency, weight-based limit, and total billed units before submission.

Maximum: 2,000 billable HCPCS units per 30 days.
Adults and adolescents at least 12 years: 1,000 IU IV every 3 to 4 days; up to 2,000 IU every 3 to 4 days may be considered for inadequate response, not exceeding 80 IU/kg.
Children 6 to 11 years: 500 IU IV every 3 to 4 days; may be adjusted up to 1,000 IU every 3 to 4 days according to response.

Denial Risk

Renewal Criteria Not Met

Renewal may be denied when the member no longer meets universal or indication-specific eligibility criteria, experiences unacceptable toxicity, or does not demonstrate clinical benefit or a documented need for dose titration.

Document continued HAE eligibility and appropriate prophylaxis use.
Document absence of severe hypersensitivity, serious thromboembolic events, or other unacceptable toxicity.
Document clinical benefit or inadequate response warranting titration, including more than 1 HAE attack per month.

HAE-nC1-INH

ConditionHereditary angioedema with normal C1 inhibitor

Laboratory findingNormal C1-INH level according to the laboratory

Qualifying evidenceA confirmed HAE-causing mutation in F12, ANGPT1, PLG, KNG1, MYOF, or HS3ST6, or recurrent angioedema attacks without hives refractory to 4 weeks of high-dose antihistamines

Non-quantitative treatment limitations (NQTLs)

DefinitionMethods, guidelines, standards of evidence, or other conditions that can restrict how long or to what extent benefits are provided under a health plan

ExamplesUtilization review and prior authorization

Application to medical benefit drugsThe utilization management NQTL applies comparably, and not more stringently, to MH/SUD and medical/surgical medical benefit prescription drugs

Confirmed HAE diagnosis

HAE-C1-INH Type 1 or 2: Current or historical C1-INH antigenic level is below the laboratory lower limit of normal; current or historical C1-INH functional level is below the laboratory lower limit of normal; or genetic testing confirms pathogenic mutation(s) in SERPING1.
HAE-nC1-INH
- Genetic or clinical pathway: Confirmed HAE-causing mutation(s) in F12, ANGPT1, PLG, KNG1, MYOF, and/or HS3ST6; or recurrent angioedema attacks without hives refractory to a 4-week trial of high-dose antihistamines.4 weeks at four times the standard dose of a second-generation H1 antagonist
- Prior therapy history: Prior beneficial response to a therapy indicated for acute HAE attacks; or inadequate response or intolerance to an adequate trial of another prophylactic HAE therapy, such as tranexamic acid, aminocaproic acid, danazol, or progestin therapy specific to females.