[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 (Systemic)

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 (Systemic) 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.

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.

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.

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.