Table 3.
Specific agents for hereditary angioedema (HAE)
| Drug (Trade name; manufacturer) | Approval for HAE | Age group | Dosage | Mechanism | Adverse events |
|---|---|---|---|---|---|
| Plasma-derived nanofiltered C1-INH (Berinert® P; CSL Behring, Kankakee, IL, USA)54,58,59 | In USA for acute facial, laryngeal, and abdominal attacks In Europe for all acute attacks and preprocedure prophylaxis |
Adolescents and adults | 20 U/kg IV | Inhibition of plasma kallikrein, coagulation factors XIIa, and XIa, C1s, C1r, MASP-1, MASP-2, and plasmin | Rare: risk of anaphylaxis Theoretical: transmission of infectious agent |
| Plasma-derived nanofiltered C1-INH (Cinryze®; ViroPharma Biologics, Exton, PA, USA)38,54,60 | In USA for routine prophylaxis In Europe for all acute attacks and short-term and long-term prophylaxis |
Adolescents and adults | 1000 U IV every 3–4 days | Inhibition of plasma kallikrein, coagulation factors XIIa, and XIa, C1s, C1r, MASP-1, MASP-2, and plasmin | Rare: risk of anaphylaxis Theoretical: transmission of infectious agent |
| Recombinant human C1-INH (Ruconest®; Pharming Group NV, Leiden, the Netherlands)38,62–64 | In Europe for acute attacks In USA, not yet approved, orphan drug, fast track status for acute attacks |
NR | 50–100 U/kg IV | Inhibition of plasma kallikrein, coagulation factors XIIa, and XIa, C1s, C1r, MASP-1, MASP-2, and plasmin | Uncommon: risk of anaphylaxis in rabbit-sensitized patients |
| Recombinant protein, ecallantide (Kalbitor; Dyax Corp, Burlington, MA, USA)66,67 | In USA for acute attacks | ≥16 years | 30 mg SC (3 injections of 10 mg each) | Inhibition of plasma kallikrein | Uncommon: risk of anaphylaxis; antidrug antibodies |
| Bradykinin B2 receptor antagonist, icatibant (Firazyr®; Shire Orphan Therapies, Inc, Lexington, MA, USA)68–70 | In USA and Europe for acute attacks | ≥18 years | 30 mg SC | Inhibition of bradykinin | Common: injection site reactions |
Notes: Data from Cicardi et al;54 Epstein and Bernstein;58 Berinert [C1 esterase inhibitor (human)] package insert;59 Varga and Farkas;62 Ruconest (Rhucin in non-European territories). Recombinant human C1 esterase inhibitor;63 Santarus Biologics License Application;64 Kalbitor (ecallantide) package insert;66 Levy et al;67 Dubois and Cohen;68 Firazyr (icatibant) package insert,69 and Schmidt, Hirschl, Trautinger.70 From The New England Journal of Medicine, Zuraw BL, Hereditary Angioedema, Volume 359, pp 1027–1036. Copyright © 2008 Massachusetts Medical Society. Adapted with permission from Massachusetts Medical Society.38
Abbreviations: C1-INH, C1 esterase inhibitor; C1r, complement component 1, r subcomponent; C1s, complement component 1, s subcomponent; IV, intravenous; MASP, mannose-binding lectin serine protease; NR, not reported; SC, subcutaneous.