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
- Treatment prevents further swelling initially and
will reverse the existing swelling prior to treatment with time
- 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:
- 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.
- 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.
- Craig T, et al. WAO Guideline for the Management of Hereditary Angioedema. World Allergy Organ J 2012;5(12):182-99.
- Nasr IH, et al. Optimizing hereditary angioedema management through tailored treatment approaches. Expert Rev Clin Immunol 2015; doi: 10.1586/1744666X.2016.1100963
- 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
- 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
May 23, 2019 at 6:41 pm
Thanks for the research, Can i share it to a friend to revalidate the data? She’s building some policies and guidelines for her hospital.
Really good work.
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October 2, 2019 at 11:32 pm
Could I please have a name of a physician who has knowledge about Hereditary Angioedema? I’ve recently need diagnosed and can not find a doctor to help me. My allergist is a nice man however, I have no help. Ended up in the ER by ambulance for my throat closing.
Thank you so much!
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