benzralizumab (Rx)

Action and Spectrum

In severe asthma with an eosinophilic pattern — known as the TH2-high phenotype — the disease process is driven by elevated levels of IL-5 and IL-13, leading to airway hyperreactivity, increased blood and airway eosinophils, high serum IgE, and good responsiveness to inhaled steroids. IL-5 is especially important because it supports eosinophil development, survival, and recruitment to the lungs by interacting with IL-5 receptors found on eosinophils, basophils, and some mast cells. 

Benralizumab works by tightly binding to the α-chain of the IL-5 receptor, blocking the pathway that sustains eosinophils. Moreover, because it lacks fucose in part of its structure, benralizumab binds strongly to FcγRIIIa receptors on natural killer cells, macrophages, and neutrophils. This interaction enhances the destruction of eosinophils through antibody-dependent cell-mediated cytotoxicity, helping to reduce inflammation in severe eosinophilic asthma. 

Drug Interaction

Adverse Reaction

Frequency defined:  

>10% 

Antibody development 

1% to 10% 

Headache 

Pharyngitis 

Fever 

Post-marketing  

Angioedema 

Hypersensitivity reaction 

Black Box Warning

There is no blackbox warning for this drug

Contraindication / Caution

Contraindications 

Hypersensitivity 

Cautions 

Hypersensitivity: May cause severe allergic reactions (anaphylaxis, angioedema, rash); can occur within hours or be delayed. Stop treatment if reaction occurs. 

Acute asthma: Not for acute asthma attacks, bronchospasm, or status asthmaticus. Seek medical help if asthma worsens. 

Corticosteroid use: Do not stop steroids suddenly. Taper doses slowly under medical supervision to avoid withdrawal or flare of suppressed conditions. 

Parasitic infections: Treat existing helminth infections before starting. If a new infection develops and doesn’t respond to treatment, stop benralizumab until resolved. 

Pregnancy / Lactation

Pregnancy consideration: only preferred if conventional therapies do not work to treat asthma in pregnancy. 

Lactation: Benzralizumab excretion in breast milk is not known. 

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 

• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 

• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women 

• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 

• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 

• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology 

In severe asthma with an eosinophilic pattern, known as the TH2-high phenotype, inflammation is driven by cytokines like IL-5 and IL-13. This leads to high IgE levels, airway hyperreactivity, and increased eosinophils in the blood and lungs, making patients generally responsive to inhaled corticosteroids. IL-5 is especially important because it supports the growth, survival, and movement of eosinophils to the airways by binding to its receptor found on eosinophils, basophils, and certain mast cells. 

Benralizumab works by attaching strongly to the α-chain of the IL-5 receptor, blocking IL-5 from activating eosinophils. Because it lacks fucose in part of its structure, benralizumab also binds well to FcγRIIIa receptors on immune cells like natural killer cells and macrophages. This trigger enhanced destruction of eosinophils through antibody-dependent cell-mediated cytotoxicity, helping to control inflammation in patients with severe eosinophilic asthma. 

Pharmacodynamics 

Eosinophils play a central role in inflammatory airway diseases and naturally undergo cell death when IL-5 is absent. By blocking the IL-5 receptor on eosinophils and basophils, benralizumab promotes their apoptosis and lowers their levels in the bloodstream. Additionally, its binding to the FcγRIIIα receptor on natural killer cells triggers antibody-dependent cell-mediated cytotoxicity, further helping to destroy eosinophils. Together, these actions lead to a marked reduction of eosinophils in the airway lining, sputum, blood, and even the bone marrow. 

Pharmacokinetics 

Absorption
After subcutaneous injection, Benralizumab shows dose-proportional kinetics, with an absorption half-life of about 3.6 days and a bioavailability of roughly 58%. Reported peak concentration (Cmax) is 82 mcg/mL with an AUC of 775 mcg·day/mL. 

Distribution
Its volume of distribution ranges from 52–93 mL/kg. For an average 70 kg person, the central volume is about 3.2 L and the peripheral volume is around 2.5 L. 

Protein Binding:
No significant plasma protein binding has been reported. 

Metabolism
Like other IgG monoclonal antibodies, Benralizumab is broken down by proteolytic enzymes throughout the body. 

Excretion/Elimination
It has linear pharmacokinetics without significant receptor-mediated clearance. Elimination occurs mainly via the reticuloendothelial system.
The estimated half-life is 15–18 days. 

Typical systemic clearance for a 70 kg individual is about 0.29 L/day. 

Adminstartion

Benralizumab is given as a subcutaneous injection under healthcare supervision. Before use, allow the pre-filled syringe or autoinjector to reach room temperature for about 30 minutes. Inspect the solution; it should be clear to slightly yellow with no large particles. Do not use if cloudy or discolored. Patients should be trained on proper injection technique and safe needle disposal. Injections can be given in the upper arm (by a caregiver or clinician) or self-administered in the thigh or abdomen. Once removed from the fridge, use within 24 hours or discard in a sharps container. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: Benzralizumab 

Pronounced: benz-ra-li-zu-ma 

Why do we use benzralizumab? 

Benzralizumab is used to treat asthma. For asthma attack use a rescue inhaler and talk with your doctor.