Table 3.
Summary of prophylactic treatments
| Generic name (trade name) | Dosage | Mechanism | Approval status | Efficacya | Potential adverse events |
|---|---|---|---|---|---|
| Plasma-derived C1-INH (Cinryze®) [35, 85] |
Adults and adolescents: 1000 U IV every 3 or 4 days Children: 500 U IV every 3 or 4 days |
C1-INH | Approved for prophylaxis in adults, adolescents, and pediatric patients aged ≥ 6 years | Normalized attack rate was 6.26 attacks/12 weeks compared with 12.73 with placebo | Rash, lightheadedness, fever |
| Plasma-derived C1-INH (Haegarda®) [34, 87] | 60 IU/kg SC twice weekly | C1-INH | Approved for prophylaxis in adults and adolescents | Mean number of attacks/month was 0.52 compared with 4.03 with placebo | Injection site reaction, hypersensitivity, nasopharyngitis, dizziness |
| Lanadelumab (Takhzyro®) [33, 88] | 300 mg SC Q2W Dosing Q4W may be considered in patients with favorable response after 6 months | Plasma kallikrein inhibitor (monoclonal antibody) | Approved for prophylaxis in adults and adolescents | Mean number of attacks/month was 0.26 compared with 1.97 with placebo | Injection site reaction, dizziness |
| Berotralstat (Orladeyo®) [36, 89] | 150 mg oral QD | Plasma kallikrein inhibitor | Approved for prophylaxis in adults and pediatric patients aged ≥ 12 years | Mean attack rate of 1.31 attacks/month compared with 2.35 attacks/month with placebo | Abdominal pain, vomiting, diarrhea, back pain |
| Danazol (Danocrine®) [95, 96] | 200 mg oral QD Dose should be titrated to the lowest clinically effective dose | 17-alpha-alkylated androgen, Mechanism unknown | Approved for the prevention of attacks of angioedema in adults | Attacks occurred in 2.2% of danazol courses compared with 93.6% of placebo courses | Weight gain, virilization, acne, menstrual abnormalities, muscle pains, headaches, fatigue, nausea, hypertension |
| Tranexamic acid (Lysteda™) [28, 97, 98] | 30–50 mg/kg QD | Antifibrinolytic | Not FDA approved | Of the 12 patients with C1-INH treated with tranexamic acid over 6 months, 6 experienced no reduction in HAE attacks, 3 experienced a moderate reduction, and 3 experienced a large reduction (> 75%) | Gastrointestinal events, myalgia/creatine kinase elevation, risk of thrombosis |
C1-INH, C1-esterase inhibitor; FDA, Food and Drug Administration; IV, intravenous; NDA, new drug application; Q2W, every 2 weeks; Q4W, every 4 weeks; QD, once daily; SC, subcutaneous. aDifferences in trial design and populations limit cross-trial comparisons