Benralizumab

Usage

• Medical Conditions: Benralizumab is prescribed as an add-on maintenance treatment for severe eosinophilic asthma in adult and pediatric patients (6 years and older) inadequately controlled despite high-dose inhaled corticosteroids and long-acting β-agonists. It is also indicated for eosinophilic granulomatosis with polyangiitis (EGPA) in adults.
• Pharmacological Classification: Monoclonal antibody (anti-IL-5), immunomodulator.
• Mechanism of Action: Benralizumab is a humanized monoclonal antibody that directly binds to the interleukin-5 receptor alpha subunit (IL-5Rα) on eosinophils. This binding leads to antibody-dependent cell-mediated cytotoxicity (ADCC) and apoptosis (programmed cell death) of eosinophils, effectively reducing their numbers in the blood and airways. Eosinophils are key inflammatory cells in asthma and EGPA pathophysiology.

Alternate Names

• International Nonproprietary Name (INN): Benralizumab
• Brand Name: Fasenra

How It Works

• Pharmacodynamics: By depleting eosinophils, benralizumab reduces airway inflammation and hyperresponsiveness, leading to improved asthma control and a decrease in exacerbation frequency. In EGPA, it reduces organ damage associated with eosinophilic inflammation.

• Pharmacokinetics:

  • Absorption: Following subcutaneous administration, benralizumab exhibits dose-proportional pharmacokinetics. Absorption is relatively slow, with a half-life of approximately 3.6 days. Absolute bioavailability is estimated to be around 58%.
  • Metabolism: As a monoclonal antibody, benralizumab is primarily eliminated through catabolism into small peptides and amino acids, similar to endogenous IgG. It is not metabolized by CYP450 enzymes.
  • Elimination: Benralizumab clearance is not dependent on renal or hepatic function.

• Mode of Action: Binds with high affinity to the IL-5Rα on the surface of eosinophils. This binding triggers ADCC, primarily mediated by natural killer (NK) cells, and also induces direct apoptosis of eosinophils.

• Receptor Binding: Specifically targets the IL-5Rα.

• Elimination pathways: Primarily by catabolism into small peptides and amino acids; not dependent on renal or hepatic pathways.

Dosage

Standard Dosage

Adults: 30 mg subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks thereafter.

Children (6 to 11 years): Dose is based on body weight. Prescribing information should be consulted for specific pediatric dosing guidance.

Children and Adolescents (12 years and older): Same as adult dosing.

Special Cases:

• Elderly Patients: No dose adjustment is necessary.
• Patients with Renal Impairment: No dose adjustment is necessary.
• Patients with Hepatic Dysfunction: No dose adjustment is necessary.
• Patients with Comorbid Conditions: No specific dose adjustments are generally recommended. However, clinical judgment should be used based on the patient’s individual circumstances.

Clinical Use Cases

Benralizumab is not indicated for:

• Intubation
• Surgical Procedures
• Mechanical Ventilation
• Intensive Care Unit (ICU) Use
• Emergency Situations (e.g., status asthmaticus, cardiac arrest)

Dosage Adjustments

No specific dosage adjustments are required for renal or hepatic impairment, elderly patients, or specific comorbid conditions.

Side Effects

Common Side Effects:

Headache, pharyngitis (sore throat), fever, injection site reactions (pain, redness, swelling, itching), fatigue, hypersensitivity reactions (rash, urticaria).

Rare but Serious Side Effects:

Anaphylaxis, angioedema.

Long-Term Effects:

Limited long-term data are available. Ongoing studies are evaluating the long-term safety profile of benralizumab.

Adverse Drug Reactions (ADR)

Anaphylaxis, angioedema, severe hypersensitivity reactions.

Contraindications

• Hypersensitivity to benralizumab or any of its components.

Drug Interactions

Limited clinical data are available on drug interactions with benralizumab. Some potential interactions have been identified, primarily with other immunomodulators. Consult a comprehensive drug interaction resource for the most up-to-date information.

Pregnancy and Breastfeeding

• Pregnancy: Limited data available. Monoclonal antibodies cross the placenta, especially during the third trimester. Use only if the potential benefit outweighs the potential risk to the fetus. A pregnancy exposure registry is available.
• Breastfeeding: It is unknown if benralizumab is excreted in human milk. Consider the benefits of breastfeeding along with the mother’s need for the drug.

Drug Profile Summary

• Mechanism of Action: IL-5Rα-directed cytolytic monoclonal antibody, depletes eosinophils.
• Side Effects: Headache, pharyngitis, injection site reactions, hypersensitivity reactions, anaphylaxis (rare).
• Contraindications: Hypersensitivity to benralizumab.
• Drug Interactions: Limited data available. Refer to a drug interaction resource.
• Pregnancy & Breastfeeding: Limited data in pregnancy; unknown if excreted in breast milk.
• Dosage: 30 mg SC q4weeks x 3 doses, then q8weeks.
• Monitoring Parameters: Eosinophil counts, asthma control, adverse events.

Popular Combinations

Benralizumab is typically used as add-on therapy to inhaled corticosteroids and long-acting beta-agonists. It is not usually combined with other biologics for asthma.

Precautions

• General Precautions: Monitor for hypersensitivity reactions, especially after the first dose. Screen for parasitic infections before starting therapy.
• Specific Populations: See Pregnancy and Breastfeeding sections.
• Lifestyle Considerations: No specific lifestyle considerations are generally associated with benralizumab therapy.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Benralizumab?

A: Adults and adolescents (12 years and older): 30 mg subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks. Children (6-11 years old): dosage is weight based and should be determined by a physician.

Q2: How is Benralizumab administered?

A: Subcutaneous injection in the upper arm, thigh, or abdomen.

Q3: What are the common side effects of Benralizumab?

A: Headache, pharyngitis, injection site reactions, fever, fatigue.

Q4: What is the mechanism of action of Benralizumab?

A: Benralizumab binds to the IL-5 receptor on eosinophils, leading to their depletion via ADCC.

Q5: Can Benralizumab be used during pregnancy or breastfeeding?

A: Limited data are available for pregnancy. Consult a physician. It is unknown if it is excreted in breast milk.

Q6: Is Benralizumab indicated for acute asthma exacerbations?

A: No, Benralizumab is not indicated for the relief of acute bronchospasm or status asthmaticus.

Q7: What should patients be monitored for during Benralizumab therapy?

A: Hypersensitivity reactions, especially after the first dose; worsening asthma symptoms; parasitic infections. Eosinophil counts can be monitored but are not required for routine management.

Q8: Does Benralizumab interact with other medications?

A: Limited data are available on drug interactions. Consult a healthcare professional and refer to a drug interaction resource.

Q9. Are there any contraindications to using Benralizumab?

A: Yes, a known hypersensitivity to benralizumab or any of its components is a contraindication.

Q10. What are the long-term effects of Benralizumab?

A: The long-term effects of Benralizumab are still being studied. However, current data suggest it is generally safe and well-tolerated.