Mepolizumab

Class: Anti-inflammatory Agents
Chemical Name: Disulfide with human-mouse monoclonal SB-240563 κ-chain, anti-(human interleukin 5) (human-mouse monoclonal SB-240563 γ1-chain) immunoglobulin G1, dimer
Molecular Formula: C₆₄₇₆H₁₀₀₈₄N₁₇₃₂O₂₀₂₈S₄₆
CAS Number: 196078-29-2
Brands: Nucala

Introduction

Antiasthmatic agent; a recombinant DNA-derived humanized interleukin-5 (IL-5) receptor antagonist monoclonal antibody and IgG₁ kappa immunoglobulin.^{1 6 7}

Uses for Mepolizumab

Asthma

Adjunctive maintenance therapy in patients with severe eosinophilic asthma.^{1 2 3 4}

Reduces asthma exacerbation rate and decreases oral corticosteroid dosage requirements.^{1 2 3 4} No effect on lung function as measured by change in baseline FEV₁.¹

Eosinophilic phenotype (i.e., eosinophilic asthma) is generally characterized by blood and sputum eosinophilia, eosinophilic inflammation, recurrent asthma exacerbations, and frequently, responsiveness to corticosteroids.^{6 8 9 11}

Not indicated for treatment of other eosinophilic conditions.¹

Not indicated for relief of acute bronchospasm or status asthmaticus.¹

Mepolizumab Dosage and Administration

Administration

Sub-Q Administration

Administer by sub-Q injection into the upper arm, thigh, or abdomen every 4 weeks by a clinician.¹

Reconstitution

Reconstitute vial containing 100 mg of mepolizumab lyophilized powder with 1.2 mL of sterile water for injection (using a 2- or 3-mL syringe with 21-gauge needle) to provide a solution containing 100 mg/mL.¹

Direct the stream of sterile water diluent onto the lyophilized powder.¹ Swirl vial gently for 10 seconds approximately every 15 seconds until completely dissolved (typically ≤5 minutes).¹ Do not shake.¹

Mechanical reconstitution device may be used to swirl the vial at 450 rpm for ≤10 minutes or at 1000 rpm for ≤5 minutes.¹

Reconstituted solution is clear to opalescent, colorless to pale yellow or pale brown, and essentially free from particulates (small air bubbles acceptable).¹

Dosage

Pediatric Patients

Asthma

Sub-Q

Adolescents ≥12 years of age: 100 mg every 4 weeks.¹

Adults

Asthma

Sub-Q

100 mg every 4 weeks.¹

Special Populations

No special population dosage recommendations at this time.¹

Cautions for Mepolizumab

Contraindications

• History of hypersensitivity to the drug or any ingredient in the formulation.¹

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity

Hypersensitivity reactions (e.g., angioedema, bronchospasm, hypotension, urticaria, rash) reported, generally occurring within hours or possibly days following administration.¹ If hypersensitivity reaction occurs, discontinue mepolizumab.¹ (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.¹ (See Advice to Patients.)

Infectious Complications

Herpes Zoster Infection

Herpes zoster infection (sometimes serious) reported.¹ Consider varicella (zoster) vaccination before starting therapy, if medically appropriate.^{1 13}

Parasitic Infection

Immune response against some parasitic (helminth) infections may be altered.¹ Not studied in patients with known parasitic infections.¹ Treat patients with preexisting parasitic (helminth) infections before initiating mepolizumab.¹ If parasitic infection occurs and does not respond to anthelmintic treatment, interrupt mepolizumab therapy until infection resolves.¹

Reduction of Corticosteroid Dosage

Do not abruptly discontinue systemic or inhaled corticosteroid therapy upon initiation of mepolizumab therapy.¹ If appropriate, reduce corticosteroid dosage gradually and supervise such reduction carefully.¹

Immunogenicity

Antibodies to mepolizumab detected in 6% of patients and associated with approximately 20% increased drug clearance.¹ No apparent correlation between anti-mepolizumab antibody titers and change in eosinophil concentrations.¹ Clinical importance of such antibodies not known.¹

Specific Populations

Pregnancy

No evidence of fetal harm in monkeys following IV mepolizumab during pregnancy.¹ Potential effects of monoclonal antibodies (e.g., mepolizumab) more likely to occur in second and third trimesters.¹

Encourage patients to enroll in pregnancy registry at 877-311-8972 or .¹

Lactation

Distributed into milk in monkeys.¹ Not known whether distributed into human milk.¹ Since IgG distributes into milk in humans, mepolizumab is expected to distribute into human milk.¹

Weigh potential risks to infants against clinical need and known benefits of breast-feeding.¹

Pediatric Use

Safety and efficacy not established in children <12 years of age.¹

Evaluated in 19 adolescent patients 12–17 years of age with asthma; adverse effect profile generally similar to that observed in adults.¹ Mean apparent clearance was 35% less than that of adults.¹

Geriatric Use

Insufficient experience in patients ≥65 years of age.¹ No overall differences in safety and efficacy relative to younger adults, but increased sensitivity cannot be ruled out.¹

Hepatic Impairment

Pharmacokinetics not studied in patients with hepatic impairment.¹

Renal Impairment

Pharmacokinetics not studied in patients with renal impairment.¹

Common Adverse Effects

Headache,¹ injection site reaction,¹ back pain,¹ fatigue,¹ influenza,¹ urinary tract infection,¹ upper abdominal pain,¹ pruritus,¹ eczema,¹ muscle spasm.¹

Interactions for Mepolizumab

No formal drug interaction studies to date.¹

Mepolizumab Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability following sub-Q injection approximately 80%.¹

Maximum plasma concentrations occurred from 4–8 days following sub-Q administration.¹²

Steady-state concentrations reached by approximately 16 weeks.¹² Twofold accumulation of drug observed at steady state.^{1 12}

Dose-proportional pharmacokinetics over a sub-Q dosage range of 12.5–250 mg.¹

Onset

Decreases in blood eosinophil count observed on the third day following sub-Q administration.^{1 7}

Duration

Following drug discontinuance, blood and sputum eosinophil counts increase within 3 months, blood eosinophil counts return to baseline over 6 months, and rate of severe asthma exacerbations increases over 3–6 months.¹⁰ Exacerbation rate no different than that with placebo after 12 months.¹⁰

Distribution

Extent

Distributed into milk in monkeys.¹ Not known whether distributed into human milk.¹ (See Lactation under Cautions.)

Elimination

Metabolism

Metabolized by widely distributed proteolytic enzymes.^{1 12}

Half-life

16–22 days.^{1 12}

Special Populations

Adolescents 12–17 years of age: Mean apparent clearance 35% less than that of adults.¹

Stability

Storage

Parenteral

Powder for Injection

<25°C.¹ Keep in original package and protect from light.¹ Do notfreeze.¹

Reconstituted solution: Use immediately or store at <30°C for up to 8 hours.¹ Do notfreeze.¹

Actions

• Recombinant DNA-derived humanized interleukin-5 (IL-5) receptor antagonist monoclonal antibody and IgG₁ kappa immunoglobulin.¹

• Inhibits IL-5 binding to the alpha chain of the IL-5 receptor complex expressed on the eosinophil cell surface.^{1 6 7 11}

• Blocks IL-5 signaling that interferes with growth, differentiation, recruitment, activation, and survival of eosinophils and decreases eosinophil-mediated inflammation.^{1 6 7 8 11}

Advice to Patients

• Risk of hypersensitivity reactions.¹ Importance of patients informing clinicians if hypersensitivity reactions (e.g., angioedema, bronchospasm, hypotension, urticaria, rash) occur.¹ (See Sensitivity Reactions under Cautions.)

• Importance of informing patients that mepolizumab does not relieve acute asthma symptoms or exacerbations.¹ Advise patients to contact their clinician if asthma remains uncontrolled or worsens after treatment initiation.¹

• Possible increased risk of herpes zoster infections.¹ Importance of patients informing clinicians if they do not have a history of varicella infection or vaccination.¹

• Importance of informing patients with asthma receiving inhaled or systemic corticosteroids 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.¹

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹ Importance of clinicians informing women about the manufacturer's pregnancy registry and encouraging patient enrollment.¹ (See Pregnancy under Cautions.)

• Importance of informing patients of other important precautionary information.¹ (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.