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!


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


  • 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


  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