What is the recommended treatment for hereditary angioedema using C1 (Complement 1) esterase inhibitor, such as Cinryze (C1 esterase inhibitor) or Berinert (C1 esterase inhibitor)?

C1 Esterase Inhibitor Treatment for Hereditary Angioedema

Plasma-derived C1 esterase inhibitor (pdC1INH) is the first-line therapy for both acute attacks and long-term prophylaxis in hereditary angioedema (HAE), with intravenous administration at 20 IU/kg being the recommended dosage for acute attacks. 1

Treatment of Acute HAE Attacks

First-Line Treatment Options

• Intravenous pdC1INH (Berinert): 20 IU/kg IV is the optimal dose for treating acute abdominal, facial, or laryngeal attacks 2, 3
• Treatment should be administered as early as possible after attack onset:
  • Treatment within <6 hours provides significantly better outcomes compared to treatment ≥6 hours after attack onset 4
  • Median time to onset of symptom relief with 20 IU/kg dose: 0.5 hours (vs. 1.5 hours with placebo) 3
  • For severe attacks, the difference is even more pronounced (0.5 vs 13.5 hours) 3

Administration and Efficacy

• pdC1INH concentrate is administered intravenously for acute attacks 5
• Efficacy by attack location:
  • Abdominal attacks: median time to relief 19.8 minutes 6
  • Facial attacks: median time to relief 28.2 minutes 6
  • Median time to complete resolution: 11.0 hours for all attack types 6

Self-Administration

• C1INH concentrates can be self-administered, which improves quality of life 7
• Patients should be properly trained in self-administration techniques 2
• Self-administered home therapy significantly improves health-related quality of life measures 7

Long-Term Prophylaxis with C1INH

Indications for Long-Term Prophylaxis

Long-term prophylaxis must be individualized based on:

• Attack frequency and severity
• Location of attacks (especially if life-threatening)
• Access to acute care
• Comorbid conditions
• Patient preference 5

C1INH for Prophylaxis

• Cinryze (pdC1INH) is approved for prophylactic therapy:

  • Starting dose: 1000 U every 3-4 days, adjusted based on response 5
  • Significantly reduces attack frequency (6.26 attacks per 12 weeks vs 12.73 with placebo) 5
  • Makes attacks milder and shorter in duration 5

• Subcutaneous C1INH is also effective for long-term prophylaxis:

  • Can reduce attacks to approximately 1 per month (compared to 4.33/month without prophylaxis) 8
  • Particularly useful for patients with poor venous access 8
  • Improves quality of life as measured by Angioedema Quality of Life questionnaire 8

Safety Considerations

Potential Side Effects and Risks

• Most common adverse reaction: dysgeusia (bad taste in mouth) 2
• Potential risks to monitor:
  • Allergic reactions (including anaphylaxis) 2
  • Blood clots (rare but possible, especially with high doses) 2
  • Theoretical risk of viral transmission (though no seroconversions have been observed for HIV, hepatitis virus, or human B19 virus) 3

Risk Factors for Blood Clots

Increased monitoring recommended for patients with:

• History of blood clotting problems
• Heart or blood vessel disease
• Stroke history
• Indwelling catheter/access device
• Immobility
• Concurrent medications that increase clotting risk (birth control pills, androgens) 2

Special Populations

Pregnancy

• pdC1INH is the preferred treatment for HAE during pregnancy 1
• Both acute attacks and prophylaxis can be managed with pdC1INH in pregnant patients 1

Pediatric Patients

• pdC1INH is approved for treatment of acute attacks in pediatric patients 2
• Dosing remains weight-based at 20 IU/kg 2

HAE with Normal C1 Inhibitor

For HAE variants with normal C1INH levels (HAE-FXII, HAE-PLG, HAE-UNK):

• pdC1INH and icatibant are both broadly used and effective on-demand treatments 5
• For HAE-FXII, icatibant shows high efficacy in 81% of patients, while pdC1INH shows high efficacy in 37.1% and moderate efficacy in 47.4% 5
• For HAE-UNK, pdC1INH shows moderate efficacy in 16.1% and mild efficacy in 74.2% of patients 5

Storage and Handling

• Keep BERINERT in original carton to protect from light
• Store at temperatures of 2-30°C (36-86°F)
• Do not freeze 2

Remember that early treatment of HAE attacks is crucial for optimal outcomes, and patients should be educated on recognizing attack symptoms and implementing their emergency action plan promptly.