What medications are used to treat angioedema?

Medications for Treating Angioedema

For treating angioedema, medication selection should be based on the specific type of angioedema, with first-line treatments including antihistamines and corticosteroids for histamine-mediated angioedema, and targeted therapies such as C1 inhibitors, icatibant, or ecallantide for bradykinin-mediated forms. 1

Classification of Angioedema Types

Angioedema can be broadly classified into two main categories, which dictate treatment approach:

1. Histamine-mediated angioedema

   • Usually presents with urticaria (hives)
   • Often associated with allergen exposure
   • Responds to antihistamines and corticosteroids

2. Bradykinin-mediated angioedema

   • Does not present with urticaria
   • Includes hereditary angioedema (HAE), acquired C1 inhibitor deficiency, and ACE inhibitor-associated angioedema
   • Resistant to antihistamines and corticosteroids

Medications for Histamine-Mediated Angioedema

• H1 antihistamines

  • First-line treatment
  • Example: Diphenhydramine 50 mg IV 1
  • Mechanism: Blocks histamine receptors

• Corticosteroids

  • First-line treatment alongside antihistamines
  • Example: Methylprednisolone 125 mg IV 1
  • Mechanism: Reduces inflammation

• Epinephrine

  • For severe cases with airway involvement
  • Used in emergency situations
  • Mechanism: Vasoconstriction and bronchodilation

Medications for Bradykinin-Mediated Angioedema

Hereditary Angioedema (HAE) Acute Attack Treatment

• Icatibant (Firazyr)

  • Bradykinin B2 receptor antagonist
  • Dosage: 30 mg subcutaneously in abdominal area
  • Can repeat at 6-hour intervals (maximum 3 injections in 24 hours) 2
  • Self-administration possible after training

• Plasma-derived C1 esterase inhibitor

  • Replaces deficient C1-INH
  • Dosage: 20 IU/kg IV 1
  • Effective for both HAE and acquired C1-INH deficiency

• Ecallantide

  • Kallikrein inhibitor
  • For acute attacks of HAE 3
  • Not for self-administration

• Fresh frozen plasma (FFP)

  • Alternative when first-line treatments unavailable
  • Dosage: 10-15 ml/kg 1
  • Contains C1-INH but also other plasma proteins

Long-Term Prophylaxis for HAE

• Plasma-derived C1-INH replacement

  • For regular prophylaxis 1

• Lanadelumab

  • Monoclonal antibody against plasma kallikrein
  • For long-term prophylaxis 1, 3

• Attenuated androgens

  • Examples: Danazol, stanozolol
  • Dosage: Danazol 100 mg alternate days to 600 mg daily 4
  • Contraindicated in pregnancy
  • Requires monitoring for side effects

• Antifibrinolytic agents

  • Example: Tranexamic acid
  • Dosage: 30-50 mg/kg/day in 2-3 divided doses (maximum 3 g/day) 4
  • Better tolerated than androgens
  • Option for children, adolescents, and possibly during pregnancy

ACE Inhibitor-Associated Angioedema

• Primary management: Discontinuation of ACE inhibitor 4

  • Cornerstone of therapy
  • May have significant time lag before resolution
  • Avoid all ACE inhibitors permanently after an episode

• Supportive care

  • Observation in controlled environment
  • Airway management if needed

• Note: Antihistamines, corticosteroids, and epinephrine have not shown efficacy 4

Special Considerations

Airway Management

• Consider early elective intubation if signs of impending airway closure
• Be prepared for emergency tracheostomy if intubation fails
• Monitor oxygen saturation to maintain levels above 92%

Pregnancy

• Androgens are contraindicated
• Plasma-derived C1-INH is preferred treatment
• Tranexamic acid may be considered after first trimester when C1-INH unavailable

High-Risk Populations

• African Americans have higher risk for ACE inhibitor-induced angioedema 4
• People over 65, women, and those with smoking history also at increased risk

Treatment Algorithm

1. Assess for urticaria

   • Present → Likely histamine-mediated → Antihistamines + corticosteroids
   • Absent → Consider bradykinin-mediated

2. If bradykinin-mediated suspected:

   • Check medication list for ACE inhibitors → Discontinue if present
   • Consider HAE or acquired C1-INH deficiency → Use targeted therapies

3. For acute attacks of HAE:

   • First-line: Icatibant or C1-INH concentrate
   • Alternative: Fresh frozen plasma if first-line unavailable

4. For long-term prophylaxis:

   • First-line: C1-INH replacement or lanadelumab
   • Second-line: Attenuated androgens or antifibrinolytic agents

Remember that bradykinin-mediated angioedema is resistant to traditional treatments for allergic reactions, and specific targeted therapies are required for effective management.