Skip to main content
HealthPartners

Coverage criteria policies

Hereditary angioedema (HAE) drug therapy – Effective 3/1/2018

These services may or may not be covered by your HealthPartners plan. Please see your plan documents for your specific coverage information. If there is a difference between this general information and your plan documents, your plan documents will be used to determine your coverage.

Administrative Process

Hereditary Angioedema medications require prior authorization from Pharmacy Administration. The setting of drug administration will be reviewed as part of the prior authorization for Commercial Products.

Note:

For all inquiries, transfer to the Medical Injectable Line (ext 26135).

Coverage

Cinryze (C1 esterase inhibitor [human]) or Haegarda (C1 esterase inhibitor [human]) are considered medically necessary for prophylaxis against attacks of hereditary angioedema (HAE) when the following criteria are met:

  1. Prescribed by a specialist such as a hematologist, allergist or immunologist; and,
  2. Appropriate age of member (> 13 for Cinrzye, >= 12 for Haegarda); and,
  3. Diagnosis of hereditary angioedema (HAE) with laboratory confirmation including one of the following:
    1. Type I defined as serum C4 < 14 mg/dL and C1 inhibitor (C1INH) < 19.9 mg/dL; or
    2. Type II defined as functional C1INH < 72%; or,
    3. A known HAE-causing C1INH mutation; and,
  4. Use is to prevent future attacks when there is a history of at least 2 attacks a month with at least one symptom of a moderate or severe attack including one of the following:
    1. airway swelling; or,
    2. nausea and vomiting or severe abdominal pain; or,
    3. facial swelling or painful distortion of the face; and,
  5. Member has failed, is intolerant to, or has a contraindication (e.g., < age 13, or pregnant, or breastfeeding) to androgen therapy; and,
  6. The drug is prescribed according to the FDA approved regimen.
  7. For commercial products only (does not apply to Medicare or Minnesota Health Care Programs products), medication administration must occur at a clinic office or home-infusion setting unless medical necessity is met based on the criteria below, supported by medical documentation:
    1. The patient has experienced a severe or life-threatening reaction with previous infusions of the same or similar products; or,
    2. The patient has a medical condition that renders him or her unstable, exceptionally complex, immunocompromised or otherwise high-risk such that continued oversight in the current facility is required; or,
    3. There are no alternative settings available to the patient as a result of both of the following:
    4. The patient is unable to use home-infusion services as documented by the physician, social worker, or infusion provider; and,
    5. The patient is unable to access alternative settings due to unreasonable distance [>30 miles] or other extenuating circumstances.

Berinert (C1 esterase inhibitor [human]), Firazyr (icatibant), Ruconest (C1 esterase inhibitor [recombinant]) or Kalbitor (ecallantide) are considered medically necessary for the treatment of acute attacks of hereditary angioedema when the following criteria are met:

  1. Prescribed by a specialist such as a hematologist, allergist or immunologist; and,
  2. Appropriate age of member (>= 12 for Kalbitor, >= 13 for Berinert and Ruconest, >= 18 for Firazyr); and,
  3. Diagnosis of hereditary angioedema (HAE) with laboratory confirmation including one of the following:
    1. Type I defined as serum C4 < 14 mg/dL and C1 inhibitor (C1INH) < 19.9 mg/dL; or
    2. Type II defined as functional C1INH < 72%; or,
    3. A known HAE-causing C1INH mutation; and,
  4. Patient must be experiencing or have a history of attacks with at least one symptom of the moderate or severe attack including one of the following:
    1. airway swelling; or,
    2. nausea and vomiting or severe abdominal pain; or,
    3. facial swelling or painful distortion of the face; and,
  5. The drug is prescribed according to the FDA approved regimen.
  6. For commercial products only (does not apply to Medicare or Minnesota Health Care Programs products), medication administration must occur at a clinic office or home-infusion setting unless medical necessity is met based on the criteria below, supported by medical documentation:
    1. The patient has experienced a severe or life-threatening reaction with previous infusions of the same or similar products; or,
    2. The patient has a medical condition that renders him or her unstable, exceptionally complex, immunocompromised or otherwise high-risk such that continued oversight in the current facility is required; or,
    3. There are no alternative settings available to the patient as a result of both of the following:
    4. The patient is unable to use home-infusion services as documented by the physician, social worker, or infusion provider; and,
    5. The patient is unable to access alternative settings due to unreasonable distance [>30 miles] or other extenuating circumstances.

Initial approvals will be for twelve months.

All reauthorizations would continue to require documented efficacy for the regimen.

Annual reauthorizations will require medical chart documentation that the patient has been seen within the past 12 months and that markers of disease are improved by therapy. These include but may not be limited to a reduction in the number and/or severity of attacks.

Definitions

Hereditary angioedema (HAE) is a rare genetic disorder resulting from an inherited deficiency or dysfunction of the C1 inhibitor. It is characterized by recurrent episodes of angioedema, without urticaria or pruritis, which most often affect the skin or the mucosal tissues of the upper respiratory and gastrointestinal tracts.

The exact mechanism(s) that lead to angioedema are not fully understood. The role of C1 inhibitor in regulating the production of the proinflammatory mediator bradykinin appears to be critical in the pathogenesis of HAE. Kallikrein is a mediator in the production of bradykinin.

Effective therapies may replace the inhibitor (administration of C1-inhibitor concentrate or fresh frozen plasma) or increase its hepatic synthesis (administration of androgens). During acute attacks the administration of kallikrein inhibitors may reduce the production of bradykinin.

Cinryze® is a C1 inhibitor, FDA-approved for routine prophylaxis against angioedema attacks in adolescent and adult patients with Hereditary Angioedema (HAE).

Berinert® is a C1 inhibitor, FDA-approved for the treatment of acute abdominal, facial, or laryngeal attacks of hereditary angioedema (HAE) in adult and adolescent patients.

Ruconest® is a C1 inhibitor, FDA-approved for the treatment of acute attacks in adult and adolescent patients with hereditary angioedema (HAE). Effectiveness was not established in HAE patients with laryngeal attacks.

Kalbitor® is a plasma kallikrein inhibitor, FDA-approved for the treatment of acute attacks of hereditary angioedema (HAE) in patients 12 years and older.

Firazyr® is a bradykinin B2 receptor antagonist indicated for treatment of acute attacks of hereditary angioedema (HAE) in adults 18 years of age and older.

Haegarda® is a plasma-derived concentrate of C1 esterase inhibitor (human), indicated for routine prophylaxis to prevent Hereditary Angioedema (HAE) attacks in adolescent and adult patients.

Setting: The type of physical site where the drug is provided. Settings include inpatient hospital, outpatient hospital, clinic office, or home-infusion.

  • Outpatient Hospital sites have physicians and practitioners on-site and are the appropriate site to manage unstable patients and patients experiencing certain moderate to severe adverse events. Hospital settings are typically the highest-cost, most-intensive, and are the highest level settings.
  • Clinic offices are lower level settings which are not outpatient hospital settings that can manage some unstable patients and patients experiencing adverse events. Physicians may or may not be readily available.
  • Home-infusion is a lower level setting, and is performed by a licensed nurse supported by a licensed pharmacy who have expertise in administering complex medications in a patient’s home. Home infusion providers regularly manage mild to moderate adverse events, and are prepared to manage severe adverse events if needed.

Codes are listed below for informational purposes only, and do not guarantee member coverage or provider reimbursement. The list may not be all-inclusive.

HCPCS Codes

Codes

Description

J0597

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

J0598

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

J1290

Injection, ecallantide, 1 mg (Kalbitor)

J1744

Injection, icatibant, 1 mg (Firazyr)

J0596

Injection, c-1 esterase inhibitor (recombinant), Ruconest, 10 units

C9015

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

J3490

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

NDC Codes

Codes

Description

63833082502

Berinert 500 unit kit

63833083501

Berinert 500 unit vial

42227008105

Cinryze 500 unit solution

47783010101

Kalbitor 10 mg/mL solution

54092070202

Firazyr 30 mg/3 mL, 1 syringe

54092070203

Firazyr 30 mg/3 mL, 3 syringes

68012035001

Ruconest 2100IU solution

68012035002

Ruconest 2100IU solution

6383382802

Haegarda 2000IU solution

6383382902

Haegarda 3000IU solution

CPT Copyright American Medical Association. All rights reserved.  CPT is a registered trademark of the American Medical Association.

Products

This information is for most, but not all, HealthPartners plans. Please read your plan documents to see if your plan has limits or will not cover some items. If there is a difference between this general information and your plan documents, your plan documents will be used to determine your coverage. These coverage criteria may not apply to Medicare Products if Medicare requires different coverage. For more information regarding Medicare coverage criteria or for a copy of a Medicare coverage policy, contact Member Services at 952-883-7979 or 1-800-233-9645.

References

  1. Cinryze prescribing information. ViroPharma Incorporated. September 2014.
  2. Berinert prescribing information. CSL Behring LLC. September 2016.
  3. Kalbitor prescribing information. Dyax Corp. March 2015.
  4. Firazyr prescribing information. Shire Orphan Therapies, Inc. December 2015.
  5. Ruconest prescribing informaiton. Salix Pharmaceuticals, Inc. February 2015.
  6. Haegarda prescribing informaiton. CSL Behring LLC. July 2017.
  7. Cicardi M, Banerji A, Bracho F, et al., Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Eng J Med 2010;363:532-41.
  8. Bowen, T. Hereditary angioedema: beyond international consensus The Canadian Society of Allergy and Clinical Immunology Dr. David McCourtie Lecture. Allergy Asthma Clin Immunol 2011;7:1.
  9. Bowen T, Cicardi M, Farkas H, et al., 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema. Allergy Asthma Clin Immunol 2010;6(1):24.
  10. Longhurst HJ, Farkas H, Craig T, et al., HAE international home therapy consensus document. Allergy Asthma Clin Immunol 2010;6:22.

Go to

Policy activity

  • 07/30/2010 - Date of origin
  • 03/01/2018 - Effective date
Review date
  • 11/2017
Revision date
  • 11/06/2017

Related content