Pharmacy Prior Authorization Criteria

Hereditary Angioedema Agents - PA, NF

Indications for Prior Authorization

Berinert (C1 esterase inhibitor [Human])

• For diagnosis of Acute treatment of Hereditary Angioedema (HAE)
  Indicated for the treatment of acute abdominal, facial, or laryngeal attacks of HAE in adult and adolescent patients.

  The safety and efficacy of Berinert for prophylactic therapy have not been established.

Cinryze (C1 esterase inhibitor [Human])

• For diagnosis of Prophylaxis of Hereditary Angioedema (HAE)
  Indicated for routine prophylaxis against angioedema attacks in adults, adolescents and pediatric patients (6 years old and above) with HAE.

• For diagnosis of Acute treatment of Hereditary Angioedema (HAE)
  Following treatment with nanofiltered C1 inhibitor concentrate (Cinryze) for an acute attack, the median time to response was 30 minutes in 82 patients with HAE. [3]

Sajazir (icatibant)

• For diagnosis of Acute treatment of Hereditary Angioedema (HAE)
  Indicated for the treatment of acute attacks of hereditary angioedema (HAE) in adults 18 years of age and older.

Firazyr (icatibant)

• For diagnosis of Acute treatment of Hereditary Angioedema (HAE)
  Indicated for the treatment of acute attacks of HAE in adults 18 years of age and older.

Haegarda (C1 esterase inhibitor [Human])

• For diagnosis of Prophylaxis of Hereditary Angioedema (HAE)
  Indicated for routine prophylaxis to prevent HAE attacks in patients 6 years of age and older.

Kalbitor (ecallantide)

• For diagnosis of Acute treatment of Hereditary Angioedema (HAE)
  Indicated for treatment of acute attacks of HAE in patients 12 years of age and older.

Orladeyo (berotralstat)

• For diagnosis of Prophylaxis of Hereditary Angioedema (HAE)
  Indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 12 years of age and older. Limitations of Use: The safety and effectiveness of ORLADEYO for the treatment of acute HAE attacks have not been established. ORLADEYO should not be used for treatment of acute HAE attacks. Additional doses or doses of ORLADEYO higher than 150 mg once daily are not recommended due to the potential for QT prolongation.

Ruconest (C1 esterase inhibitor [Recombinant])

• For diagnosis of Acute treatment of Hereditary Angioedema (HAE)
  Indicated for the treatment of acute attacks in adult and adolescent patients with HAE. Limitation of Use: Effectiveness was not established in HAE patients with laryngeal attacks.

Takhzyro (lanadelumab-flyo)

• For diagnosis of Prophylaxis of Hereditary Angioedema (HAE)
  Indicated for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 2 years and older.

Criteria

Cinryze

Prior Authorization (Initial Authorization)

Length of Approval: 12 Month(s)
For diagnosis of Prophylaxis of HAE attacks

• Diagnosis of hereditary angioedema (HAE) [A]
AND
• One of the following [A]:
• Diagnosis has been confirmed by C1 inhibitor (C1-INH) deficiency or dysfunction (Type I or II HAE) as documented by ONE of the following:
• C1-INH antigenic level below the lower limit of normal
• C1-INH functional level below the lower limit of normal
OR
• Diagnosis has been confirmed by both of the following:
• Patient has normal C1-INH levels (HAE-n1-C1INH previously referred to as HAE Type 3)
AND
• One of the following
• Confirmed presence of a FXII, plasminogen gene mutation, angiopoietin-1 mutation, or kininogen mutation
• Patient has recurrent angioedema attacks that are refractory to high-dose antihistamines (e.g., cetirizine) with a confirmed family history of recurrent angioedema
AND
• For prophylaxis against HAE attacks [3]
AND
• Not used in combination with other approved treatments for prophylaxis against HAE attacks
AND
• Patient is 6 years of age or older
AND
• Prescribed by or in consultation with one of the following: [B]
• Immunologist
• Allergist

Cinryze

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)
For diagnosis of Prophylaxis of HAE attacks

• Patient demonstrates positive clinical response to therapy (e.g., reduction in the number or rate of HAE attacks while on therapy)
AND
• Not used in combination with other approved treatments for prophylaxis against HAE attacks

Cinryze [off-label], Sajazir

Prior Authorization (Initial Authorization)

Length of Approval: 12 Month(s)
For diagnosis of Treatment of acute HAE attacks

• Diagnosis of hereditary angioedema (HAE) [A]
AND
• One of the following [A]:
• Diagnosis has been confirmed by C1 inhibitor (C1-INH) deficiency or dysfunction (Type I or II HAE) as documented by one of the following:
• C1-INH antigenic level below the lower limit of normal
• C1-INH functional level below the lower limit of normal
OR
• Diagnosis has been confirmed by both of the following:
• Patient has normal C1-INH levels (HAE-n1-C1INH previously referred to as HAE Type 3)
AND
• One of the following:
• Confirmed presence of a FXII, plasminogen gene mutation, angiopoietin-1 mutation, or kininogen mutation
• Patient has recurrent angioedema attacks that are refractory to high-dose antihistamines (e.g., cetirizine) with a confirmed family history of recurrent angioedema
AND
• For the treatment of acute HAE attacks [3, C]
AND
• Not used in combination with other approved treatments for acute HAE attacks
AND
• One of the following:
• Patient is 6 years of age or older (applies to Cinryze only)
• Patient is 18 years of age or older (applies to Sajazir only)
AND
• Prescribed by or in consultation with one of the following: [B]
• Immunologist
• Allergist

Cinryze [off-label], Sajazir

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)
For diagnosis of Treatment of acute HAE attacks

• Patient demonstrates positive clinical response to therapy
AND
• Not used in combination with other approved treatments for acute HAE attacks

Berinert

Prior Authorization (Initial Authorization)

Length of Approval: 12 Month(s)
For diagnosis of Treatment of acute HAE attacks

• Diagnosis of hereditary angioedema (HAE) [3, A]
AND
• One of the following [A]:
• Diagnosis has been confirmed by C1 inhibitor (C1-INH) deficiency or dysfunction (Type I or II HAE) as documented by one of the following:
• C1-INH antigenic level below the lower limit of normal
• C1-INH functional level below the lower limit of normal
OR
• Diagnosis has been confirmed by both of the following:
• Patient has normal C1-INH levels (HAE-n1-C1INH previously referred to as HAE Type 3)
AND
• One of the following:
• Confirmed presence of a FXII, plasminogen gene mutation, angiopoietin-1 mutation, or kininogen mutation
• Patient has recurrent angioedema attacks that are refractory to high-dose antihistamines (e.g., cetirizine) with a confirmed family history of recurrent angioedema
AND
• For the treatment of acute HAE attacks [3, C]
AND
• Not used in combination with other approved treatments for acute HAE attacks
AND
• Prescribed by or in consultation with one of the following: [B]
• Immunologist
• Allergist

Berinert

Prior Authorization (Reauthorization)

Length of Approval: 12 Month(s)
For diagnosis of Treatment of acute HAE attacks

• Patient demonstrates positive clinical response to therapy
AND
• Not used in combination with other approved treatments for acute HAE attacks

Haegarda, Orladeyo or Takhzyro

Non Formulary

Length of Approval: 12 Month(s)
For diagnosis of Prophylaxis of HAE attacks

• Diagnosis of hereditary angioedema (HAE) [A]
AND
• Submission of medical records (e.g., chart notes) confirming one of the following [A]:
• Diagnosis has been confirmed by C1 inhibitor (C1-INH) deficiency or dysfunction (Type I or II HAE) as documented by ONE of the following:
• C1-INH antigenic level below the lower limit of normal
• C1-INH functional level below the lower limit of normal
OR
• Diagnosis has been confirmed by both of the following:
• Patient has normal C1-INH levels (HAE-n1-C1INH previously referred to as HAE Type 3)
AND
• One of the following
• Confirmed presence of a FXII, plasminogen gene mutation, angiopoietin-1 mutation, or kininogen mutation
• Patient has recurrent angioedema attacks that are refractory to high-dose antihistamines (e.g., cetirizine) with a confirmed family history of recurrent angioedema
AND
• For prophylaxis against HAE attacks [3]
AND
• Submission of medical records (e.g., chart notes) or absence of paid claims confirming drug is not used in combination with other approved treatments for prophylaxis against HAE attacks
AND
• One of the following:
• Patient is 6 years of age or older (Applies to Haegarda only)
• Patient is 12 years of age or older (Applies to Orladeyo only)
• Patient is 2 years of age or older (Applies to Takhzyro only)
AND
• One of the following (Applies to Haegarda and Takhzyro only):
• Paid claims or submission of medical records (e.g., chart notes) confirming a trial and failure, contraindication or intolerance to Cinryze
OR
• Both of the following:
• Paid claims or submission of medical records (e.g., chart notes) confirming continuation of prior therapy, defined as no more than a 45-day gap in therapy
• Patient demonstrates positive clinical response to therapy
AND
• Prescribed by or in consultation with one of the following: [B]
• Immunologist
• Allergist

Firazyr, Kalbitor, Ruconest

Non Formulary

Length of Approval: 12 Month(s)
For diagnosis of Treatment of acute HAE attacks

• Diagnosis of hereditary angioedema (HAE) [A]
AND
• Submission of medical records (e.g., chart notes) confirming one of the following [A]:
• Diagnosis has been confirmed by C1 inhibitor (C1-INH) deficiency or dysfunction (Type I or II HAE) as documented by one of the following:
• C1-INH antigenic level below the lower limit of normal
• C1-INH functional level below the lower limit of normal
OR
• Diagnosis has been confirmed by both of the following:
• Patient has normal C1-INH levels (HAE-n1-C1INH previously referred to as HAE Type 3)
AND
• One of the following:
• Confirmed presence of a FXII, plasminogen gene mutation, angiopoietin-1 mutation, or kininogen mutation
• Patient has recurrent angioedema attacks that are refractory to high-dose antihistamines (e.g., cetirizine) with a confirmed family history of recurrent angioedema
AND
• For the treatment of acute HAE attacks [3, C]
AND
• Submission of medical records (e.g., chart notes) or absence of paid claims confirming drug is not used in combination with other approved treatments for acute HAE attacks
AND
• One of the following:
• Patient is 18 years of age or older (applies to Firazyr only)
• Patient is 12 years of age or older (applies to Kalbitor only)
AND
• One of the following:
• Both of the following:
• Paid claims or submission of medical records (e.g., chart notes) confirming a trial and failure, or intolerance to one of the following:
• generic icatibant
• Sajazir
AND
• Paid claims or submission of medical records (e.g., chart notes) confirming a trial and failure, or intolerance to Berinert
OR
• Both of the following:
• Paid claims or submission of medical records (e.g., chart notes) confirming continuation of prior therapy, defined as no more than a 45-day gap in therapy
• Patient demonstrates positive clinical response to therapy
AND
• Prescribed by or in consultation with one of the following: [B]
• Immunologist
• Allergist

P & T Revisions

2024-10-18, 2024-04-08, 2023-11-01, 2023-10-31, 2023-04-05, 2023-03-31, 2022-04-04, 2021-11-29, 2021-10-05, 2021-08-02, 2021-05-19, 2021-03-02, 2021-02-19, 2020-11-18, 2020-06-30, 2020-02-18, 2019-09-03

References

1. Cinryze Prescribing Information. Shire ViroPharma, Inc. Lexington, MA. February 2023.
2. Micromedex Healthcare Series [internet database]. Greenwood Village (CO): Thomson Reuters (Healthcare) Inc. Updated periodically. Available at: http://www.thomsonhc.com/. Accessed July 30, 2019.
3. Berinert Prescribing Information. CSL Behring, LLC. Kankakee, IL. September 2021.
4. FDA/CDER. Briefing Document for Blood products Advisory Committee. Presented May 2, 2008. Available at: http://www.fda.gov/. Accessed July 30, 2019.
5. Craig TJ, Levy RJ, Wasserman RL. Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks. J Allergy Clin Immunol. Oct 2009;124(4):801-8.
6. Cicardi M, Zura B. Hereditary angioedema: Pathogenesis and diagnosis. UpToDate Web site. Available at: http://www.uptodate.com/. Accessed July 30, 2019.
7. Sajazir Prescribing Information. Cipla Ltd., India. May 2022.
8. Busse PJ, Christiansen SC, et. al. US HAEA Medical Advisory Board 2020 Guidelines for the Management of Hereditary Angioedema. J Allergy Clin Immunol Pract 2020.
9. Firazyr Prescribing Information. Takeda Pharmaceuticals America, Inc., Lexington, MA . January 2024.
10. Haegarda Prescribing Information. CSL Behring LLC. Kankakee, IL . January 2022.
11. Kalbitor Prescribing Information.Takeda Pharmaceuticals America, Inc. Lexington, MA. December 2020.
12. Orladeyo Prescribing Information. BioCryst Pharmaceuticals, Inc. Durham, NC. November 2023.
13. Ruconest Prescribing Information. Pharming Healthcare Inc. Warren NJ . April 2020.
14. Takhzyro Prescribing Information.Takeda Pharmaceuticals U.S.A., Inc. Lexington, MA . February 2023.

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End Notes

1. HAE is a rare genetic disorder that can be broadly divided into two fundamental types: 1) HAE-C1INH (HAE Type 1 or Type 2), which presents with a deficiency of C1-INH; 2) HAE-n1-C1INH (previously referred to as HAE Type 3), a rare variant which presents with normal C1-INH levels. This condition is inherited in an autosomal dominant manner characterized by recurrent episodes of angioedema, without urticaria or pruritus, which most often affect the skin or mucosal tissues of the upper respiratory and gastrointestinal tracts. Diagnosis of Type 1 or Type 2 HAE requires laboratory testing to confirm low or abnormal levels of C1-inhibitor. HAE-n1-C1INH (previously referred to as HAE Type 3) presents a diagnostic challenge given the current lack of a validated biochemical test to confirm diagnosis. Per HAE guidelines, when a diagnosis of HAE-n1-CINH is suspected based on normal C1-INH levels, diagnosis should be confirmed by a known mutation associated with the disease or a positive family history of recurrent angioedema with a lack of efficacy to high-dose antihistamine therapy [10, 14].
2. Includes immunologist and allergist specialties to ensure the requirement for proper diagnosing and assessing the severity of the symptoms. In the pivotal Cinryze trial, criteria for participation of long term prophylaxis included patients 9 years and older with documented HAE (based on: a low C4 level plus low C1 inhibitor antigenic level/or low C1 inhibitor functional level OR a known HAE causing mutation) AND a history of at least two HAE attack per month. [1, 8] Berinert is approved for the treatment of acute attacks in patients who are 13 years and older. In the pivotal Berinert trial patients had laboratory-confirmed C1-inhibitor deficiency (type I or II HAE). [9]
3. Following treatment with nanofiltered C1 inhibitor concentrate (Cinryze) for an acute attack, the median time to response was 30 minutes in 82 patients with hereditary angioedema (median number of attacks per patient, 3; range, 1 to 57 attacks) in an open-label extension trial (median follow-up of 11 months). Additionally, 93% of attacks responded within 4 hr after C1 inhibitor concentrate treatment. [3]

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Revision History

• 2024-10-18: update guideline
• 2024-04-08: update guideline
• 2023-11-01: Updated initial criteria. Added reauthorization criteria. Updated background.
• 2023-10-31: update guideline
• 2023-04-05: Annual review: Updated Takhzyro criteria age requirement. Added new 150 mg/mL syringe formulation of Takhzyro (GPI 8584204020E510) to existing Takhzyro criteria. Updated references and background/indications.
• 2023-03-31: Updated GPIs
• 2022-04-04: Added new Takhzyro GPI for prefilled syringe. Annual review: Updated background and references.
• 2021-11-29: background update
• 2021-10-05: Added Sajazir to GL and updated the embedded step for Firazyr to be a trial of one of the following: generic icatibant or Sajazir.
• 2021-08-02: Addition of embedded step through generic icatibant for brand Firazyr only
• 2021-05-19: Addition of EHB formulary to guideline, no changes to criteria
• 2021-03-02: 2021: No changes
• 2021-02-19: updated guideline to add criteria for newly approved drug Orladeyo to guideline. Updated existing criteria for both the prophylactic agents and acute treatment agents
• 2020-11-18: Updated Haegarda indication section for expanded age indication; no criteria changes
• 2020-06-30: Revised guideline to add new Berinert criteria.
• 2020-02-18: 2020 Annual Review
• 2019-09-03: Added generic Firazyr (icatibant) and updated background.

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