Benralizumab (Monograph)

Brand name: Fasenra
Drug class: Interleukin Antagonists

Medically reviewed by Drugs.com on Jun 18, 2023. Written by ASHP.

[Web]

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 ≥12 years of age with severe eosinophilic asthma.

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

Not indicated for treatment of other eosinophilic conditions.

Not indicated for relief of acute bronchospasm or status asthmaticus.

Several clinical practice guidelines on asthma management are available, including the Global Initiative for Asthma (GINA) guidelines. In GINA, stepwise approach to treatment is recommended where specific drugs are added or adjusted up or down through a series of steps (1 through 5) to achieve symptom control while keeping the patient on the lowest effective treatment.

Biologic agents such as benralizumab are generally recommended as add-on therapy for severe asthma.

Benralizumab Dosage and Administration

General

Pretreatment Screening

• Screen for pre-existing parasitic helminth infections and treat infections prior to initiating benralizumab.

Patient Monitoring

• Monitor for hypersensitivity reactions after administration of benralizumab. Discontinue benralizumab if hypersensitivity reactions occur.

Other General Considerations

• Intended for use under guidance of a healthcare provider.

• Do not abruptly discontinue systemic or inhaled corticosteroids (ICS) upon initiation of benralizumab therapy. Decrease corticosteroid dosages gradually, if appropriate, under the direct supervision of a prescriber.

Administration

Sub-Q Administration

Administer by sub-Q injection into the upper arm, thigh, or abdomen.

Commercially available in prefilled syringes and autoinjectors. Prefilled syringe intended for administration by a clinician. Autoinjector pen may be administered by patient or caregiver after proper training provided and healthcare provider determines it is appropriate.

Remove syringe or autoinjector from refrigerator and allow to sit at room temperature for about 30 minutes prior to injection; use within 24 hours or discard.

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.

Prescribing Limits

Special Populations

Geriatric Patients

The manufacturer makes no specific dosage recommendations for geriatric patients.

Hepatic Impairment

The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.

Renal Impairment

The manufacturer makes no specific dosage recommendations for patients with renal impairment.

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.

Deterioration of Disease and Acute Episodes

Not indicated for treatment of acute asthma symptoms or exacerbations, acute bronchospasm, or status asthmaticus.

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.

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.

Registry information is available by calling 1-877-311-8972 or visiting [Web].

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

Common adverse effects (≥5%): headache, pharyngitis.

Drug Interactions

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.

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.

• Importance of patients and/or caregivers receiving training on proper administration technique using the benralizumab autoinjector pen.

• 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.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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.

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Frequently asked questions

• What type of asthma is Fasenra used to treat?

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