benralizumab

Brand: Fasenra

Prototype: mepolizumab
Drug Class: biologic — anti-interleukin-5 receptor alpha (anti-IL-5Ralpha) monoclonal antibody
Drug Family: biologic
Subclass: anti-eosinophilic biologic — IL-5Ralpha antagonist
Organ Systems: respiratoryimmunology

Mechanism of Action

Humanized monoclonal antibody that directly binds the alpha subunit of the IL-5 receptor on eosinophils and basophils; binding recruits natural killer cells (via enhanced ADCC via afucosylated Fc region), causing direct eosinophil apoptosis and depletion; reduces eosinophil counts to near-zero levels, eliminating eosinophilic airway inflammation.

interleukin-5 receptor alpha (IL-5Ralpha) on eosinophils and basophils

Indications

  • severe eosinophilic asthma (add-on maintenance therapy, adults and adolescents 12 years or older)
  • eosinophilic granulomatosis with polyangiitis (EGPA)

Contraindications

  • hypersensitivity to benralizumab

Adverse Effects

Common

  • injection site reactions
  • headache
  • pharyngitis
  • hypersensitivity reactions (urticaria, rash)

Serious

  • anaphylaxis (rare)
  • helminth infections (eosinopenia may impair defense against parasites)

Pharmacokinetics (ADME)

Absorption subcutaneous injection; bioavailability approximately 59%; Tmax approximately 7 days
Distribution Vd approximately 3.0-3.4 L; IgG1 distribution
Metabolism proteolytic degradation to amino acids and peptides
Excretion proteolytic catabolism; no renal or hepatic clearance
Half-life approximately 15.5 days
Onset eosinophil depletion within 24-48 hours; clinical benefit over weeks
Peak approximately 7 days post-injection
Duration doses every 8 weeks after initial loading doses
Protein Binding N/A (monoclonal antibody)
Vd approximately 3.0-3.4 L

Drug Interactions

Drug / Agent Mechanism Severity
live vaccines immunosuppression from eosinophil depletion may reduce vaccine response; avoid live vaccines during therapy moderate

Nursing Considerations

  1. Administer 30 mg subcutaneously every 4 weeks for 3 doses, then every 8 weeks; refrigerate and allow to reach room temperature for 30 minutes before injection; do not shake — gently roll vial.
  2. Observe patients for 30-60 minutes after the first two injections to detect hypersensitivity reactions; epinephrine and resuscitation equipment should be available in the administration setting.
  3. Screen for parasitic infections (especially in endemic areas) before initiating benralizumab; eosinophil depletion may impair the immune response to helminth infections.
  4. Instruct patients that benralizumab is an add-on maintenance therapy that does not replace ICS, LABA, or rescue SABA therapy; acute asthma attacks require conventional rescue treatment.

Clinical Pearls

  • Benralizumab's mechanism of directly causing eosinophil apoptosis (via ADCC) is unique compared with mepolizumab and reslizumab, which only block IL-5 signal transduction; this direct depletion achieves near-complete eosinophil reduction and may be more effective in high eosinophil burden disease.
  • The every-8-week maintenance dosing schedule (after loading) is one of the least frequent injection schedules among biologics for asthma, improving real-world adherence relative to monthly injection regimens.

Safety Profile

Pregnancy avoid
Lactation insufficient-data
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Guideline Update pending