CurrentEmblemHealthPolicy N/A

Berinert (C1 esterase inhibitor, human) Intravenous — Treatment of acute Hereditary Angioedema (HAE) attacks

Defines medical necessity, dosing, authorization limits, and renewal criteria for IV Berinert to treat acute abdominal, cutaneous (facial), or laryngeal HAE attacks. Applies to EmblemHealth/ConnectiCare members and prescribing providers.

Policy Summary

PayerEmblemHealth

PolicyBerinert (C1 esterase inhibitor, human) Intravenous — Treatment of acute Hereditary Angioedema (HAE) attacks

Policy CodePolicy N/A

Change TypeCriteria review and operational updates

Effective Date

Next Review Date

Key ActionSubmit preauthorization with specialist documentation, repeat blood testing confirming HAE subtype, confirmation of avoidance of known medication triggers, and attack history to support approval and renewal.

SourceLink

POLICY UPDATE CHANGES

Removed prior age restriction of 'at least 6 years of age' on 2024-04-01.

Added avoidance of DPP‑IV inhibitors and neprilysin inhibitors as triggers to be confirmed (07/25/2023).

Annual Review no criteria changes as of 2025-02-27.

12Initial authorization length

1100Max billable units per 28 days

4 attacksSupply authorized to cover

J0597

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Medical Necessity Criteria for Berinert (acute HAE attacks)

Initial Approval Criteria — Treatment of acute abdominal, facial, or laryngeal HAE attacks

Covered when ALL of the following are met:

ALL of the following

Prescribed by, or in consultation with, a specialist in allergy, immunology, hematology, pulmonology, or medical genetics
ALL of the following
- Estrogen-containing oral contraceptive agents AND hormone replacement therapy
- Antihypertensive agents containing ACE inhibitors
- Dipeptidyl peptidase IV (DPP‑IV) inhibitors (e.g., sitagliptin)
- Neprilysin inhibitors (e.g., sacubitril)
Patient has a history of moderate to severe cutaneous attacks without concomitant hives OR abdominal attacks OR mild to severe airway swelling attacks of HAE (i.e., debilitating cutaneous/gastrointestinal symptoms OR laryngeal/pharyngeal/tongue swelling)
Clinical description required
ANY of the following
- ALL of the following
  - Low C1‑INH antigenic level (below lab-specific lower limit of normal)
  - Low C4 level (below lab-specific lower limit of normal)
  - Low C1‑INH functional level (below lab-specific lower limit of normal)
  - ANY of the following
    Patient has a family history of HAE
    Onset of HAE symptoms occurred before age 30

Renewal Criteria

Authorization may be renewed when ALL of the following are met:

ALL of the following

Patient continues to meet the initial criteria
Significant improvement in severity and duration of attacks has been achieved and sustained
Absence of unacceptable toxicity from the drug (examples: hypersensitivity reactions, serious thrombotic events, laryngeal HAE attacks)
Provider must document absence of unacceptable adverse events
Cumulative amount of HAE medications on-hand is considered; authorization will provide sufficient quantity to treat up to 4 acute attacks per 4 weeks for duration of authorization

Authorization and Dosing Thresholds

Authorization supply targetSufficient quantity to treat up to 4 acute attacks per 4 weeks

Max billable units1100 billable units per 28 days

Dose per attack20 IU/kg IV per recognized HAE attack

Relevant Billing and Diagnosis Codes

Applicable Procedure/Drug CodeHCPCSCovered

J0597

Injection, C-1 esterase inhibitor (human), Berinert, 10 units

Applicable NDCsNDCCovered

63833-0825-xx

Berinert 500 IU single-use vial

Relevant ICD-10 DiagnosisICD-10Covered

D84.1

Defects in the complement system

What the Provider Must Do

Prior Authorization

Preauthorization required with clinical documentation

Treating physician must submit clinical evidence that the member meets criteria for Berinert prior to authorization. Documentation should demonstrate specialist involvement (prescribed by or in consultation with allergy, immunology, hematology, pulmonology, or medical genetics), confirmation the patient is avoiding listed triggers, a history of qualifying HAE attacks, and subtype confirmation via repeat blood testing. Include HCPCS code J0597 on the request for the drug.

Include HCPCS J0597 (Injection, C1 esterase inhibitor (human), Berinert, 10 units).
Document specialist prescribing or consultation (allergy, immunology, hematology, pulmonology, or medical genetics).
Confirm avoidance of estrogen therapy, ACE inhibitors, DPP‑IV inhibitors, and neprilysin inhibitors.
Provide attack history (cutaneous without hives, abdominal, or airway swelling) and repeat blood testing confirming HAE subtype.

Documentation Required

Clinical and Operational Background

Berinert (C1 esterase inhibitor, human) is an intravenous formulation indicated for treatment of acute hereditary angioedema (HAE) attacks. The recommended dose for treatment of an acute HAE attack is 20 IU/kg IV administered upon recognition of an attack (dose per attack = 20 IU/kg IV). (See dosing/administration and indication details.)

Authorization requires laboratory confirmation of the patient’s HAE subtype and involvement of an appropriate specialist: the drug must be prescribed by, or in consultation with, a specialist in allergy, immunology, hematology, pulmonology, or medical genetics. Repeat blood testing must document the specific laboratory pattern for the suspected subtype (HAE I, HAE II, or HAE with normal C1‑INH) as described in the policy (C1‑INH antigenic level, C4, C1‑INH functional level, and C1q as applicable). For HAE with normal C1‑INH, repeat testing during an attack plus either a known HAE‑causing mutation or family history with documented lack of response to high‑dose antihistamines and corticosteroids is required.

Prior to approval the provider must confirm avoidance of known medication triggers for HAE attacks, including estrogen-containing oral contraceptives and hormone replacement therapy, ACE inhibitors, DPP‑IV inhibitors (e.g., sitagliptin), and neprilysin inhibitors (e.g., sacubitril). The clinician must also document an appropriate clinical history consistent with moderate to severe cutaneous, abdominal, or airway swelling attacks.

Supply and authorization limits are specified: initial coverage is provided for 12 weeks and renewals require documentation of continued benefit and absence of unacceptable toxicity. The cumulative amount of on‑hand HAE medication will be considered when authorizing and the policy authorizes a supply sufficient to treat up to 4 acute attacks per 4 weeks with a maximum of 1100 billable units per 28 days.

This policy was last reviewed on 2025-02-27 with no clinical criteria changes. Operational updates since prior reviews include removal of the previous age restriction (removed 2024-04-01) and addition of confirmation that patients are avoiding DPP‑IV inhibitors and neprilysin inhibitors as potential triggers (added 07/25/2023).

Defined Terms

Definitions

HAE IHereditary Angioedema due to C1‑INH deficiency: low C1‑INH antigenic level, low C4, and low C1‑INH functional level.

HAE IIHereditary Angioedema due to C1‑INH dysfunction: normal to elevated C1‑INH antigenic level, low C4, and low C1‑INH functional level.

HAE with normal C1‑INH (HAE III)Normal C1‑INH antigenic and functional levels and normal C4; diagnosis supported by repeat testing during an attack confirming no abnormalities and either a known HAE‑causing mutation or family history plus documented lack of efficacy of chronic high‑dose antihistamine therapy and corticosteroids.

Policy Changes / Notes

2025-02-27annual_reviewLatest

Annual review completed with no changes to the clinical criteria.

2024-04-01criteria_revision

Removed prior age restriction of 'at least 6 years of age'.

2023-07-25criteria_added

Added requirement to confirm avoidance of DPP‑IV inhibitors (e.g., sitagliptin) and neprilysin inhibitors (e.g., sacubitril) as possible triggers for HAE attacks.

Policy Summary

PayerEmblemHealth

PolicyBerinert (C1 esterase inhibitor, human) Intravenous — Treatment of acute Hereditary Angioedema (HAE) attacks

Policy CodePolicy N/A

Change TypeCriteria review and operational updates

Effective Date

Next Review Date

SourceLink

On This Page

ALL of the following

Normal to elevated C1‑INH antigenic level
Low C4 level (below lab-specific lower limit of normal)
Low C1‑INH functional level (below lab-specific lower limit of normal)

ALL of the following

Normal C1‑INH antigenic level
Normal C4 level
Normal C1‑INH functional level
Repeat blood testing during an attack confirms no abnormal lab values indicative of HAE I or II
ANY of the following
- Known HAE‑causing mutation (e.g., F12, angiopoietin‑1, plasminogen)
- Family history of HAE AND documented evidence of lack of efficacy of chronic high‑dose antihistamine therapy (e.g., cetirizine up to 4x daily or equivalent for at least 1 month or interval sufficient to expect ≥3 angioedema attacks) AND corticosteroids

Laboratory confirmation required

Repeat laboratory testing is required to confirm the HAE subtype. For HAE I and II, provide C1‑INH antigenic level, C1‑INH functional level, and C4 with results relative to the laboratory's lower limit of normal; include C1q when specified. For HAE with normal C1‑INH, repeat blood testing during an attack to exclude HAE I/II is required plus either genetic testing demonstrating a known HAE‑causing mutation or family history with documented failure of chronic high‑dose antihistamine therapy and corticosteroids.

HAE I: low C1‑INH antigenic level, low C4, low C1‑INH functional level (per lab lower limit of normal); C1q as applicable.
HAE II: normal/elevated C1‑INH antigenic level, low C4, low C1‑INH functional level.
HAE with normal C1‑INH: normal C1‑INH antigenic, C4, and functional levels; repeat testing during an attack to exclude I/II; plus known mutation OR family history + documented antihistamine failure and corticosteroids.

Documentation Required

Medication reconciliation / trigger avoidance

Provider must document that the patient is avoiding known medication triggers for HAE prior to approval. The record should confirm discontinuation or avoidance of estrogen therapy, ACE inhibitors, DPP‑IV inhibitors, and neprilysin inhibitors when applicable.

Estrogen-containing oral contraceptives and hormone replacement therapy.
Antihypertensive agents containing ACE inhibitors.
DPP‑IV inhibitors (e.g., sitagliptin).
Neprilysin inhibitors (e.g., sacubitril).

Prior Authorization

Renewal documentation

For renewal requests, include HCPCS J0597 and documentation that the member continues to meet initial criteria, has sustained significant improvement in severity and/or duration of attacks, has no unacceptable toxicity, and the cumulative on‑hand medication quantity justifies renewed supply (authorization supports up to 4 attacks per 4 weeks).

Document continued fulfillment of initial approval criteria.
Provide evidence of sustained clinical improvement in attack severity/duration.
Document absence of unacceptable toxicity (e.g., hypersensitivity, serious thrombotic events).
Report current on‑hand HAE medication quantities to justify supply (authorization intended to cover up to 4 attacks per 4 weeks).