Benralizumab

Class: Interleukin Antagonists
Brands: Fasenra

Medically reviewed on Nov 20, 2017

Introduction

Benralizumab is an interleukin antagonist.

Uses for Benralizumab

Benralizumab has the following uses:

Benralizumab is an interleukin-5 receptor alpha-directed cytolytic monoclonal antibody (IgG1, kappa) indicated for the add-on maintenance treatment of severe asthma in patients 12 years of age and older, and with an eosinophilic phenotype.¹

Benralizumab has the following limitations of use:

Not for treatment of other eosinophilic conditions.¹

Not for relief of acute bronchospasm or status asthmaticus.¹

Benralizumab Dosage and Administration

General

Benralizumab is available in the following dosage form(s) and strength(s):

Injection: 30 mg/mL solution in a single-dose prefilled syringe.¹

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

• Administer by subcutaneous injection.¹

• Recommended dose is 30 mg every 4 weeks for the first 3 doses, followed by once every 8 weeks thereafter.¹

Cautions for Benralizumab

Contraindications

Known hypersensitivity to benralizumab or excipients.¹

Warnings/Precautions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, rash) have occurred following administration of benralizumab. These reactions generally occur within hours of administration, but in some instances have a delayed onset (i.e., days). In the event of a hypersensitivity reaction, benralizumab should be discontinued.¹

Acute Asthma Symptoms or Deteriorating Disease

Benralizumab should not be used to treat acute asthma symptoms or acute exacerbations. Do not use benralizumab to treat acute bronchospasm or status asthmaticus. Patients should seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with benralizumab.¹

Reduction of Corticosteroid Dosage

Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with benralizumab. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.¹

Parasitic (Helminth) Infection

Eosinophils may be involved in the immunologic response to some helminth infections. Patients with known helminth infections were excluded from participation in clinical trials. It is unknown if benralizumab will influence a patient’s response against helminth infections.¹

Treat patients with pre-existing helminth infections before initiating therapy with benralizumab. If patients become infected while receiving treatment with benralizumab and do not respond to anti-helminth treatment, discontinue treatment with benralizumab until infection resolves.¹

Specific Populations

Pregnancy

Risk Summary: The data on pregnancy exposure from the clinical trials are insufficient to inform on drug-associated risk. Monoclonal antibodies such as benralizumab are transported across the placenta during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy. In a prenatal and postnatal development study conducted in cynomolgus monkeys, there was no evidence of fetal harm with IV administration of benralizumab throughout pregnancy at doses that produced exposures up to approximately 310 times the exposure at the maximum recommended human dose (MRHD) of 30 mg given by subcutaneous injection. ¹ In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.¹

Clinical Considerations: In women with poorly or moderately controlled asthma, evidence demonstrates that there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. The level of asthma control should be closely monitored in pregnant women and treatment adjusted as necessary to maintain optimal control.¹

Animal Data: In a prenatal and postnatal development study, pregnant cynomolgus monkeys received benralizumab from beginning on gestational day 20 (GD20) to GD22 (dependent on pregnancy determination), on GD35, once every 14 days thereafter throughout the gestation period and 1-month postpartum (maximum 14 doses) at doses that produced exposures up to approximately 310 times that achieved with the MRHD (on an AUC basis with maternal IV doses up to 30 mg/kg once every 2 weeks). Benralizumab did not elicit adverse effects on fetal or neonatal growth (including immune function) up to 6.5 months after birth. There was no evidence of treatment-related external, visceral, or skeletal malformations. Benralizumab was not teratogenic in cynomolgus monkeys. Benralizumab crossed the placenta in cynomolgus monkeys. Benralizumab concentrations were approximately equal in mothers and infants on postpartum day 7, but were lower in infants at later time points. Eosinophil counts were suppressed in infant monkeys with gradual recovery by 6 months postpartum; however, recovery of eosinophil counts was not observed for one infant monkey during this period.¹

Lactation

There is no information regarding the presence of benralizumab in human or animal milk, and the effects of benralizumab on the breast-fed infant and on milk production are not known. However, benralizumab is a humanized monoclonal antibody (IgG1 kappa class), and immunoglobulin G (IgG) is present in human milk in small amounts. If benralizumab is transferred into human milk, the effects of local exposure in the gastrointestinal tract and potential limited systemic exposure in the infant to benralizumab are unknown. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for benralizumab and any potential adverse effects on the breast-fed child from benralizumab or from the underlying maternal condition.¹

Pediatric Use

There were 108 adolescents 12 to 17 years of age with asthma enrolled in the Phase 3 exacerbation trials (Trial 1: n=53, Trial 2: n=55). Of these, 46 received placebo, 40 received benralizumab every 4 weeks for 3 doses, followed by every 8 weeks thereafter, and 22 received benralizumab every 4 weeks. Patients were required to have a history of 2 or more asthma exacerbations requiring oral or systemic corticosteroid treatment in the past 12 months and reduced lung function at baseline (pre-bronchodilator FEV₁ <90%) despite regular treatment with medium- or high-dose inhaled corticosteroids and long-acting β-adrenergic agonists with or without oral corticosteroids or other controller therapy. The pharmacokinetics of benralizumab in adolescents 12 to 17 years of age were consistent with adults based on population pharmacokinetic analysis, and the reduction in blood eosinophil counts was similar to that observed in adults following the same benralizumab treatment. The adverse event profile in adolescents was generally similar to the overall population in the Phase 3 studies. The safety and efficacy in patients younger than 12 years of age has not been established.¹

Geriatric Use

Of the total number of patients in clinical trials of benralizumab, 13% (n = 320) were 65 years of age and over, while 0.4% (n=9) were 75 years of age and over. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.¹

Common Adverse Effects

Most common adverse reactions (incidence greater than or equal to 5%) include headache and pharyngitis.¹

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

No formal drug interaction studies have been conducted.¹

Actions

Mechanism Of Action

Benralizumab is a humanized afucosylated, monoclonal antibody (IgG1, kappa) that directly binds to the alpha subunit of the human interleukin-5 receptor (IL-5Rα) with a dissociation constant of 11 pM. The IL-5 receptor is expressed on the surface of eosinophils and basophils. In an in vitro setting, the absence of fucose in the Fc domain of benralizumab facilitates binding (45.5 nM) to FcγRIII receptors on immune effector cells, such as natural killer (NK) cells, leading to apoptosis of eosinophils and basophils through antibody-dependent cell-mediated cytotoxicity (ADCC).¹

Inflammation is an important component in the pathogenesis of asthma. Multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) are involved in inflammation. Benralizumab, by binding to the IL-5Rα chain, reduces eosinophils through ADCC; however, the mechanism of benralizumab action in asthma has not been definitively established.¹

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (patient information). ¹

Inform patients that hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, rash) have occurred after administration of benralizumab. These reactions generally occurred within hours of benralizumab administration, but in some instances had a delayed onset (i.e., days). Instruct patients to contact their healthcare professional if they experience symptoms of an allergic reaction.¹

Inform patients that benralizumab does not treat acute asthma symptoms or acute exacerbations. Inform patients to seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with benralizumab.¹

Inform patients to not discontinue systemic or inhaled corticosteroids except under the direct supervision of a physician. Inform patients that reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.¹

Additional Information

AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

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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