C1 Esterase Inhibitor (Cinryze®)
42227-0081-XX Cinryze 500MG UNIT SOLR – (VIROPHARMA)
C1 esterase inhibitor (C1-INH) is a normal constituent of human blood and is a serine proteinase inhibitor or serpin. C1-INH’s primary function is to regulate the activation of the complement and intrinsic coagulation pathway. It also has a role in regulation of the fibrinolytic system.
Individuals with an inherited deficiency of C1-INH suffer from sudden, recurrent edematous swellings of the subcutaneous or submucosal tissues. This condition is known as hereditary angioedema (HAE).
Commercially, C1-INH is available in two forms, those derived from purified human plasma which has undergone multiple viral reduction steps and a recombinant analogue purified from the milk of transgenic rabbits. Cinryze® is a human plasma-derived product formulated for prevention of angioedema attacks.
C1 Esterase Inhibitor - Cinryze® for the prevention of angioedema attacks of Hereditary Angioedema (HAE) is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
C1 Esterase Inhibitor - Cinryze® for the treatment or prevention of other conditions/diseases is considered investigational.
C1 Esterase Inhibitor - Cinryze® is considered medically appropriate if ALL of the following criteria are met:
Individual is 6years of age or older
Individual has history of ANY ONE of the following criteria for long-term HAE prophylaxis:
History of two (2) or more severe HAE attacks per month (e.g., airway swelling, debilitating cutaneous or gastrointestinal episodes)
Individual disabled more than five days per month by HAE attacks
History of at least one laryngeal attack caused by HAE
“On demand” HAE therapy (e.g., Kalbitor®, Firazyr®, Berinert®, Ruconest®) does not offer satisfactory control or access to “on-demand therapy” is limited
Not used in combination with C1 inhibitor prophylaxis (e.g., Haegarda or Takhzyro)
Confirmation of avoidance of the following possible triggers of HAE attacks:
Estrogen-containing oral contraceptive agents AND hormone replacement therapy
Antihypertensive agents containing ACE inhibitors
Individual has ANY ONE of the following clinical presentations consistent with HAE subtype, which must be confirmed by repeat blood testing:
HAE I (C1-Inhibitor deficiency) if ALL of the following:
Low C1 inhibitor (C1-INH) antigenic level (C1-INH antigenic level below the lower limit of normal as defined by the laboratory performing the test)
Low C4 level (C4 below the lower limit of normal as defined by the performing lab)
C1-INH functional level low (C1-INH functional level below the lower limit of normal as defined by the performing lab) and ANY ONE of the following:
Individual positive family history of HAE
Onset of HAE symptoms occurred before age 30
Normal C1q level
HAE II (C1-Inhibitor dysfunction) if ALL of the following:
Normal to elevated C1-INH antigenic level
Low C4 (C4 below the lower limit of normal as defined by the performing lab)
Low C1-INH functional level (C1-INH functional level below the lower limit of normal as defined by the performing lab)
HAE with normal C1-INH (formerly known as HAE III)prophylaxis for HAE with normal C1-INH is not routinely recommended and will be evaluated on a case by case basis.
C1 Esterase Inhibitor - Cinryze® is considered medically appropriate for renewal if ALL of the following criteria are met:
Individual continues to meet initial approval criteria
Absence of unacceptable toxicity from the drug, e.g., severe hypersensitivity reactions, serious thrombotic events, laryngeal attacks, etc. and ANY ONE of the following:
Significant improvement in severity and duration of attacks have been achieved and sustained
Individual requires dose titration due to an inadequate response to therapy (> 1.0 HAE attack/month, regardless of severity/duration)
|INDICATION(S)||DOSAGE & ADMINISTRATION|
|Hereditary Angioedema (HAE)||
Adult/adolescents (>12 years old)
1,000 units by intravenous injection every 3 to 4 days
For patients who have not responded adequately to initial dosing, doses up to 2,500 U (not exceeding 100 U/kg) every 3 or 4 days may be considered based on individual patient response.
Pediatric patients (6 to 11 years old)
500 units by intravenous injection every 3 to 4 days
The dose may be adjusted according to individual patient response, up to 1,000 U every 3 to 4 days.
LENGTH OF AUTHORIZATION
Coverage will be provided for 12 months and may be renewed.
Refer to DOSAGE LIMITS below
APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS
BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
For appropriate chemotherapy regimens, dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) published by the National Comprehensive Cancer Network®, Drugdex Evaluations of Micromedex Solutions at Truven Health, or The American Hospital Formulary Service Drug Information).
Bowen, T., Cicardi, M., Farkas, H., Bork, K., Longhurst, H. J.. Zuraw, B. et al. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema. Allergy Asthma & Clinical Immunology 2010. AACI Journal;6 (1):24.
Lexi-Comp Online. (2018). AHFS DI. C1 Esterase Inhibitor. Retrieved November 21, 2018 from Lexi-Comp Online with AHFS.
MICROMEDEX Healthcare Series. Drugdex Evaluations. (2018, July). C1 Esterase Inhibitor. Retrieved November 21, 2018 from MICROMEDEX Healthcare Series.
U. S. Food and Drug Administration. (2018, June). Center for Biologics Evaluation and Research. Cinryze® C1 Esterase Inhibitor (Human) label. Retrieved November 21, 2018 from http://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/UCM129918.pdf.
ORIGINAL EFFECTIVE DATE: 6/13/2009
MOST RECENT REVIEW DATE: 4/2/2019
Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.
This document has been classified as public information.
Maximum billable units per dose and over time by indication as a Medical Benefit 1 billable unit = 10 units