Benralizumab

Class: Interleukin Antagonists
- Antiasthmatic Agents
Chemical Name: Disulfide with human-mouse monoclonal MEDI-563 κ-chain, anti-(human interleukin 5 receptor α-chain) (human-mouse monoclonal MEDI-563 heavy chain), immunoglobulin G1, dimer
Molecular Formula: C₆₄₉₂H₁₀₀₆₀N₁₇₂₄O₂₀₂₈S₄₂
CAS Number: 1044511-01-4
Brands: Fasenra

Medically reviewed by Drugs.com on Feb 1, 2022. Written by ASHP.

Introduction

Antiasthmatic agent; a recombinant DNA-derived afucosylated humanized monoclonal antibody specific for the alpha chain of the interleukin-5 (IL-5) receptor (IL-5Rα) and an IgG₁ kappa immunoglobulin.

Uses for Benralizumab

Asthma

Adjunctive maintenance therapy in patients with severe eosinophilic asthma.

Reduces asthma exacerbation rate, decreases oral corticosteroid dosage requirements, and improves FEV₁ from baseline.

Eosinophilic phenotype (i.e., eosinophilic asthma) generally characterized by blood and sputum eosinophilia, eosinophilic inflammation, recurrent asthma exacerbations, and, frequently, responsiveness to corticosteroids.

Not indicated for treatment of other eosinophilic conditions.

Not indicated for relief of acute bronchospasm or status asthmaticus.

Benralizumab Dosage and Administration

General

Monitor patients for hypersensitivity reactions after administration. (See Hypersensitivity under Cautions.)

Administration

Sub-Q Administration

Administer by sub-Q injection into the upper arm, thigh, or abdomen; intended for administration by a clinician.

Commercially available in prefilled syringes.

Remove syringe from refrigerator and allow to sit at room temperature for about 30 minutes prior to injection; use within 24 hours or discard. (See Storage under Stability.)

Contains no preservatives; intended for single use only.

Inject entire contents of prefilled syringe (1 mL providing 30 mg).

Dosage

Pediatric Patients

Asthma

Sub-Q

Adolescents ≥12 years of age: Initially, 30 mg every 4 weeks for 3 doses followed by 30 mg every 8 weeks.

Adults

Asthma

Sub-Q

Initially, 30 mg every 4 weeks for 3 doses followed by 30 mg every 8 weeks.

Special Populations

No special population dosage recommendations at this time.

Cautions for Benralizumab

Contraindications

History of hypersensitivity to benralizumab or any ingredient in the formulation.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity

Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, rash) reported, generally occurring within hours or possibly days following administration. If hypersensitivity reaction occurs, discontinue benralizumab. (See Contraindications under Cautions.)

Deterioration of Disease and Acute Episodes

Not indicated for treatment of acute asthma symptoms or exacerbations, acute bronchospasm, or status asthmaticus. (See Advice to Patients.)

Reduction of Corticosteroid Dosage

Do not abruptly discontinue systemic or inhaled corticosteroid therapy upon initiation of benralizumab therapy. If appropriate, reduce corticosteroid dosage gradually and supervise such reduction carefully.

Parasitic Infection

Immune response against some parasitic (helminth) infections may be altered. Not studied in patients with known parasitic infections. Treat patients with preexisting parasitic (helminth) infections before initiating benralizumab. If parasitic infection occurs and does not respond to anthelmintic treatment, interrupt benralizumab therapy until infection resolves.

Immunogenicity

Potential for immunogenicity. Development of anti-benralizumab antibodies detected in 13% of patients and associated with increased drug clearance and increased blood eosinophil concentrations; development of neutralizing antibodies also detected. Evidence of an association between anti-benralizumab antibodies and efficacy or safety of the drug not observed. (See Special Populations under Pharmacokinetics: Elimination.)

Specific Populations

Pregnancy

No evidence of fetal harm in monkeys following IV benralizumab during pregnancy. Potential effects of monoclonal antibodies (e.g., benralizumab) on the fetus more likely to occur in the third trimester.

Lactation

Not known whether distributed into human milk. Since IgG distributes into milk in humans, benralizumab is expected to distribute into human milk.

Consider benefits of breast-feeding and importance of drug to the woman; also consider potential adverse effects on the breast-fed child from the drug or underlying maternal condition.

Pediatric Use

Safety and efficacy not established in children <12 years of age.

Evaluated in 62 adolescent patients 12–17 years of age with asthma; adverse effect profile generally similar to that observed in adults.

Geriatric Use

No overall differences in safety and efficacy in patients ≥65 years of age relative to younger adults, but increased sensitivity cannot be ruled out.

Hepatic Impairment

Pharmacokinetics not studied in patients with hepatic impairment.

Renal Impairment

Pharmacokinetics not studied in patients with renal impairment.

Common Adverse Effects

Headache, pharyngitis, pyrexia, hypersensitivity reactions.

Interactions for Benralizumab

No formal drug interaction studies to date.

Drugs Metabolized by Hepatic Microsomal Enzymes

CYP substrates: Pharmacokinetic interactions unlikely.

Drugs Affected by Efflux Transport Systems

Substrates of efflux transport systems: Pharmacokinetic interactions unlikely.

Benralizumab Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability following sub-Q administration approximately 58%.

Relatively slow absorption with an absorption half-life of approximately 3.6 days following sub-Q administration.

Dose-proportional pharmacokinetics over a sub-Q dosage range of 20–200 mg and an IV dosage range of 0.03–3 mg/kg.

Onset

Decreased blood eosinophil count observed 24 hours after IV administration.

Duration

Decreased blood eosinophil count reported to last for at least 8–12 weeks.

Special Populations

Age, sex, and tobacco smoking history did not affect pharmacokinetics of benralizumab in healthy volunteers or those with asthma.

Distribution

Extent

Not known whether distributed into human milk. (See Lactation under Cautions.)

Potential for limited distribution into extravascular tissues.

Elimination

Metabolism

Metabolized by widely distributed proteolytic enzymes.

Elimination Route

Not excreted renally. No evidence of clearance through a target receptor-mediated pathway.

Half-life

Approximately 15 days following sub-Q administration.

Special Populations

Hepatic impairment: Changes in hepatic function not expected to influence clearance.

Renal impairment: Comparable clearance in patients with Cl_cr between 30–80 mL/minute and those with normal renal function. Limited data in those with Cl_cr <30 mL/minute.

Anti-benralizumab antibody titers ≥400: 4.6-fold increase in drug clearance.

Age, gender, and race did not affect clearance.

Stability

Storage

Parenteral

Injection

2–8°C in original package and protect from light. Do not freeze or shake.

Actions

Recombinant DNA-derived afucosylated humanized monoclonal antibody specific for the alpha chain of the interleukin-5 (IL-5) receptor (IL-5Rα) and an IgG₁ kappa immunoglobulin.
Inhibits activation of IL-5R and subsequent signal transduction. Induces direct, rapid, and nearly complete depletion of eosinophils and basophils in the circulation, bone marrow, and target tissues through antibody-dependent cell-mediated cytotoxicity.
Results in dose-dependent decreases in blood eosinophil counts; effects observed after 24 hours and lasting at least 8–12 weeks.
Results in associated reductions in blood basophil counts; clinical benefit of such reductions unknown.

Advice to Patients

Risk of hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, rash). Instruct patients to immediately contact a clinician if they experience symptoms of an allergic reaction. (See Hypersensitivity under Cautions.)
Importance of informing patients that benralizumab does not relieve acute asthma symptoms or exacerbations. Advise patients to contact their clinician if asthma remains uncontrolled or worsens after treatment initiation.
Importance of informing patients with asthma receiving inhaled or systemic corticosteroid therapy not to discontinue or reduce corticosteroid dosage, since withdrawal symptoms or worsening of asthma may occur; change corticosteroid dosage only under direct supervision of a clinician.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.