By Natalija Farrell, PharmD, BCPS, DABAT

*Editor’s Note: This is the first post from our wonderful ED Pharmacist colleagues, and by our in-house toxicologist no less!

Background:

Hereditary angioedema (HAE) is a rare genetic disorder that results in recurrent episodes of well-demarcated angioedema attacks without urticaria

  • Results in C1 inhibitor (C1-INH) deficiency (HAE-1) or dysfunction (HAE-2)
  • Less commonly, the C1-INH is normal (HAE-3)
  • HAE attacks are bradykinin mediated
  Signs and Symptoms Treatment
Laryngeal Attacks Laryngeal edema, upper airway obstruction On Demand Therapy, Intubation
Gastrointestinal (GI) Attacks GI colic, nausea, vomiting, diarrhea , bowel wall edema, debilitating pain On Demand Therapy
Cutaneous Attacks Edema of the extremities, torso, face, and genitalia that results in functional impairment On Demand Therapy

On Demand Treatment Options:

  • Early recognition and treatment is essential
  • Onset of treatment effect is ~30-60 minutes
    • Treatment prevents further swelling initially and will reverse the existing swelling prior to treatment with time
      • Do not delay intubation for on demand treatment with HAE laryngeal attacks
  • 2nd dose of therapy  is not warranted unless HAE attack begins to worsen
  • Available on-demand treatments have not been studied head-to-head
  • For certain on demand treatments, patients are instructed to have them readily accessible (e.g. ecallantide)
  • Fresh Frozen Plasma (FFP) or solvent detergent-treated plasma (SDP) is only recommended if treatment specific on-demand options are not available
  • Depending on the presentation, additional adjunct therapy may be needed (e.g. IV fluids, analgesics, antiemetics, etc)
  Dose Admin Repeat Dose Mechanism Adverse Effects
pdC1-INH (Berinert) 20 units/kg IV   (round to the nearest 500 units) IV at 4 ml/min 2 hours Inhibits plasma kallikrein, coagulation factors XIIa and Xia, C1s, C1r, MASP-1, MASP-2, and plasmin Well tolerated (Nausea, Headache, Fever)
pdC1-INH (Cinryze) 1000 units IV   Repeat 1000 units in 2 hours PRN IV at 1 ml/min 2 hours (same as above) Well tolerated (Nausea, Headache, Fever)
rhC1-INH (Ruconest) 50 units/kg IV  [max:  4200 units] Slow IV push over 5 minutes 2 hours   Max 4200 units/24 hr Relapse not reported (same as above) Hypersensitivity reactions (rabbit), Headache, Nausea, Diarrhea
Ecallantide (Kalbitor) 30 mg SC     3, 10mg SC injections at separate sites preferably in the abdomen   Max:  60mg/24 hr Max:  2 doses/24 hr As early as 1 hr Inhibits plasma kallikrein Hypersensitivity reaction (rare), Prolonged PTT, Headache, Nausea, Diarrhea, Fatigue
Icatibant (Firazyr) 30 mg SC   May repeat 2nd dose in 6 hr (max of 3 doses/day) Slow SC preferably in the abdomen 6 hour Max:  3 doses/24 hr Bradykinin B2 receptor antagonist Local injection site reactions, Abdominal pain, Nausea, Headache, Dizziness, Fever, Asthenia, Increased transaminases
Fresh Frozen Plasma (FFP) ~2 units IV Administer via standard Y blood infusion set N/A Inhibits plasma kallikrein, coagulation factors XIIa and Xia, C1s, C1r, MASP-1, MASP-2, and plasmin Sudden worsening of HAE attacks, Infusion reactions, Possible transmission of infectious agents

Summary:

  • HAE attacks are a potentially life-threatening medical emergency
  • Early recognition and treatment of HAE attacks is essential
  • Be familiar with which HAE on demand treatments are available at your institution
    • Due to cost and utilization considerations, FFP may be the only option at your institution
    • Consider establishing patient-specific treatment protocols in patients with known HAE that utilize your institution

References:

  1. Zuraw BL, et al. US hereditary angioedema association medical advisory board 2013 recommendations for the management of hereditary angioedema due to C1 inhibitor deficiency.  J Allergy Clin Immunol:  In Practice 2013;1:458-67.
  2. Craig T, et al. A focused parameter update:  hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor associated angioedema. J Allergy Clin Immunol 2013;131(6):1491-3.
  3. Craig T, et al. WAO Guideline for the Management of Hereditary Angioedema. World Allergy Organ J 2012;5(12):182-99.
  4. Nasr IH, et al. Optimizing hereditary angioedema management through tailored treatment approaches. Expert Rev Clin Immunol 2015; doi: 10.1586/1744666X.2016.1100963
  5. Wu MA, et al. Current treatment options for hereditary angioedema due to C1 inhibitor deficiency. Expert Opinion on Pharmacotherapy 2015; doi:  10.1517/14656566.2016.1104300
  6. Zanichelli A, et al. The safety of treatments for angioedema with hereditary C1 inhibitor deficiency. Expert Opin Drug Safety 2015;doi:  10.1517/14740338.2015.1094053