C1 Inhibitor, Ecallantide CFU

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C1 Inhibitor, Ecallantide CFU

     ??C1 (Esterase) Inhibitor (Berinert, Cinryze?), Ecallantide (Kalbitor)

    for Hereditary Angioedema

    Criteria for Use

    December 2010

    VA Pharmacy Benefits Management Services, Medical Advisory Panel, and VISN Pharmacist Executives The following recommendations are based on medical evidence, clinician input, and expert opinion. The content of the document is dynamic and will be revised as new information becomes available. The purpose of this document is to assist practitioners in clinical decision-making, to standardize and improve the quality of patient care, and to promote cost-effective drug prescribing. The clinician should utilize this guidance and interpret it in the clinical context of the individual patient. Individual cases that are outside the recommendations should be adjudicated at the local facility according to the policy and procedures of its P&T Committee and Pharmacy Services. The Product Information should be consulted for detailed prescribing information. The VA National PBM-MAP-VPE Drug Monograph for C1 ??Esterase Inhibitor (Berinert), C1 Inhibitor (Cinryze?), and Ecallantide (Kalbitor) are available at or for further information. Note: when recommendations for C1 Inhibitor appear in the document, this includes both C1 Esterase Inhibitor ?(Berinert) and C1 Inhibitor (Cinryze?).

    ? History of life-threatening acute hypersensitivity or anaphylaxis to C1 inhibitor or ecallantide ? Angioedema or abdominal pain not associated with C1 inhibitor deficiency

    ? Restricted to Allergy/Immunology, Dermatology, or for use in Emergency Medicine/Urgent Care ? Diagnosis of Hereditary Angioedema (HAE) (must fulfill at least ONE of the following) ? Type I [low serum complement factor 4 (C4), low C1 inhibitor protein]

    ? Type II (low C4, normal or increased C1 inhibitor protein, low C1 inhibitor function) ? Positive family history HAE and symptoms consistent with HAE (e.g., recurrent angioedema without urticaria, recurrent unexplained abdominal pain/vomiting, laryngeal edema)

     AND ONE of the following Indications a ? SevereAcute HAE (C1 Inhibitor or Ecallantide) [e.g., respiratory symptoms or laryngeal involvement, severe abdominal attack (severe pain with nausea and vomiting), significant orofacial swelling]

    ? Long-Term Prophylaxis (C1 Inhibitor only)

    ? Intolerance, contraindication to, or inefficacy (e.g., > 2 per month used as inclusion criteria in clinical trials) with at least one other treatment b,crecommended for long-term prophylaxis HAE attacks


    ? Frequent acute attacks despite On-Demand therapy with C1 inhibitor


    ? Extensive education provided with patient and/or caregiver demonstration of understanding, and ability and willingness to administer C1 inhibitor treatment

    ? On-Demand (C1 Inhibitor only)

    ? Frequent (e.g., > 1 every 3 weeks used as inclusion criteria in observational study) severe HAE attacks despite prophylaxis with, or not on ccprophylaxis due to intolerance or contraindication to, attenuated androgens or antifibrinolytics AND

    ? Extensive education provided with patient and/or caregiver demonstration of understanding, and ability and willingness to administer C1 inhibitor treatment

    ? Short-Term Prophylaxis (C1 Inhibitor only)

    ? Major procedure or intubation AND cc? Intolerance, contraindication to, or inefficacy with previous trial of either attenuated androgens; antifibrinolytics; or fresh frozen plasma

    aTreatment with C1 inhibitor or ecallantide in patients presenting with moderate HAE attack symptoms should be determined on a case by case basis (e.g., patient may respond to supportive care, symptom management, increased doses of attenuated androgens or antifibrinolytics); fresh frozen plasma also a treatment option for acute HAE bMay be appropriate to consider On-Demand therapy with C1 inhibitor prior to implementing Long-Term Prophylaxis with C1 inhibitor, as indicated cVA National Formulary agents include: attenuated androgens (danazol); antifibrinolytics (aminocaproic acid)

    Refer to Product Information

    August 2010; Update December 2010 1 of 2 Updated versions may be found at

     Criteria for Use: C1 Inhibitor and Ecallantide Evaluate for signs or symptoms of anaphylaxis and other symptoms of hypersensitivity (hives, urticaria, chest tightness, wheezing, hypotension) ;

    ; C1 Inhibitor: Evaluate for signs or symptoms of thrombosis (new onset swelling or pain in limbs or abdomen, new onset chest pain or shortness of breath, loss of feeling or mobility, or altered speech or consciousness) ISSUES FOR CONSIDERATION

    ; FDA Approved Indications ?C1 Inhibitor (Berinert) is approved for treatment of acute abdominal or facial attacks of hereditary angioedema (HAE) in adults and adolescents C1 Inhibitor (Cinryze?) is approved for routine prophylaxis against angioedema attacks in adolescent and adult patients with HAE Ecallantide is approved for the treatment of acute attacks of HAE in patients > 16 years of age

    ; Treatment of acquired angioedema with C1 inhibitor or ecallantide is off-label and should be adjudicated on a case by case basis ; Patients with a history of angiotensin-converting enzyme inhibitor (ACEI) associated angioedema would not be expected to respond to treatment with C1 inhibitor as these patients have normal levels of C4 and functional C1 inhibitor; there is insufficient evidence to recommend treatment with C1 inhibitor for ACEI-induced angioedema at this time. Ecallantide is currently being studied for treatment of ACEI-induced angioedema and is not recommended until clinical trial results are available demonstrating benefit for this indication ; Patients being considered for self-administration of C1 inhibitor either for On-Demand therapy or Long-Term Prophylaxis should receive education on the disease, indications for treatment with C1 inhibitor, documentation of symptoms, and proper preparation and administration of C1 inhibitor and be able to demonstrate understanding, and the ability and willingness to administer C1 inhibitor. Due to the potential for anaphylaxis, ecallantide should be administered by a healthcare professional with medical support available and is not appropriate for self-administration in On-Demand therapy or Long-Term Prophylaxis

    ; Since C1 inhibitor is derived from human blood it has the potential risk for transmitting infectious diseases including viruses and Creutzfeldt-Jakob disease. Screening and testing measures as well as manufacturing processes have been implemented to reduce this risk. If it is felt that an infection could possibly be the result of C1 inhibitor administration, this should be reported by the provider to the manufacturer and to VA ADERS. The risk vs. benefit of treatment with C1 inhibitor should also be discussed with the patient. There is no concern for viral transmission with ecallantide as it is not derived from human plasma; however, ecallantide is a recombinant protein and seroconversion to anti-ecallantide antibodies has been reported, which may occur more frequently with increased exposure to the drug

    ; C1 inhibitor and ecallantide are Pregnancy Category C: patients should be provided contraceptive counseling and education on potential risk ?vs. benefit of taking C1 inhibitor (Berinert or Cinryze?) or ecallantide if they were to become pregnant

    August 2010; Update December 2010 2 of 2 Updated versions may be found at

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