Mepolizumab

Class: Interleukin Antagonists
- Antiasthmatic 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

Medically reviewed by Drugs.com on Aug 16, 2021. Written by ASHP.

Introduction

Disease-modifying agent used in severe eosinophilic asthma and other eosinophilic conditions; a recombinant DNA-derived humanized interleukin-5 (IL-5) receptor antagonist monoclonal antibody and IgG₁ kappa immunoglobulin.

Uses for Mepolizumab

Asthma

Adjunctive maintenance therapy in patients with severe eosinophilic asthma.

Reduces asthma exacerbation rate and decreases oral corticosteroid dosage requirements. No effect on lung function as measured by change in baseline FEV₁.

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

Not indicated for relief of acute bronchospasm or status asthmaticus.

Eosinophilic Granulomatosis with Polyangiitis

Treatment of eosinophilic granulomatosis with polyangiitis (also known as Churg-Strauss syndrome); designated an orphan drug by FDA for the treatment of this condition.

Increases rate and duration of remission, reduces relapse rate, and decreases oral corticosteroid dosage requirements.

Hypereosinophilic Syndrome

Treatment of hypereosinophilic syndrome of at least 6 months' duration and without an identifiable nonhematologic secondary cause; designated an orphan drug by FDA for the treatment of this condition.

Reduces incidence and rate of disease flares.

Mepolizumab Dosage and Administration

General

Restricted Distribution

Available only through a limited network of specialty pharmacies and distributors. Consult the Nucala website for US healthcare professionals ([Web]) or call 844-468-2252 for information on how to obtain the drug.

Administration

Administer by sub-Q injection; do not administer IV.

Commercially available as an injection in single-use prefilled syringes and autoinjectors; may be self-administered. Also available as lyophilized powder in single-use vials; must be reconstituted and administered by a clinician.

Sub-Q Administration

Administer by sub-Q injection into the upper arm, thigh, or abdomen (except within 2 inches of the navel). Avoid injection into areas where the skin is tender, bruised, erythematous, or indurated.

Mepolizumab Injection

Single-use prefilled syringes and autoinjectors containing mepolizumab injection (100 mg/mL) are for use in adults and adolescents ≥12 years of age. May be self-administered. Provide patients and/or caregivers with proper training on how to administer the drug using the prefilled syringes or autoinjectors. Consult manufacturer's labeling for detailed instructions. Administer injections into the thigh or abdomen; may use upper arm if a caregiver or clinician is administering the injection.

Prior to use, allow the prefilled syringe or autoinjector to sit at room temperature, away from direct sunlight, for 30 minutes; do not use other warming methods. Inspect visually for particulate matter or discoloration. Solution should appear clear to opalescent, and colorless to pale yellow or pale brown; discard if cloudy, discolored, or contains particulates. Do not use the prefilled syringe or autoinjector if dropped on a hard surface.

Mepolizumab Lyophilized Powder

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.

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

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

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

Withdraw appropriate dose (1 mL for a 100-mg dose or 0.4 mL for a 40-mg dose) into a syringe and administer sub-Q into the upper arm, thigh, or abdomen.

Vials are for single use only; discard any unused portions of reconstituted solution.

Dosage

If a dose is missed, administer the missed dose as soon as possible and administer the next dose on the usual day of administration. If it is time for the next scheduled dose, skip the missed dose and administer the scheduled dose as planned.

Pediatric Patients

Asthma

Sub-Q

Children 6–11 years of age: 40 mg once every 4 weeks.

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

Hypereosinophilic Syndrome

Sub-Q

Adolescents ≥12 years of age: 300 mg (given as 3 consecutive 100-mg doses administered at least 2 inches apart) once every 4 weeks.

Adults

Asthma

Sub-Q

100 mg once every 4 weeks.

Eosinophilic Granulomatosis with Polyangiitis

Sub-Q

300 mg (given as 3 consecutive 100-mg doses administered at least 2 inches apart) once every 4 weeks.

Hypereosinophilic Syndrome

Sub-Q

300 mg (given as 3 consecutive 100-mg doses administered at least 2 inches apart) once every 4 weeks.

Special Populations

No special population dosage recommendations at this time.

Cautions for Mepolizumab

Contraindications

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

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity

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

Infectious Complications

Herpes Zoster Infection

Herpes zoster infection (sometimes serious) reported. Consider varicella (zoster) vaccination before starting therapy, if medically appropriate.

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 mepolizumab. If parasitic infection occurs and does not respond to anthelmintic treatment, interrupt mepolizumab therapy until infection resolves.

Reduction of Corticosteroid Dosage

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

Immunogenicity

Development of anti-mepolizumab antibodies reported. Neutralizing antibodies reported in one patient receiving mepolizumab for asthma; no neutralizing antibodies detected in patients receiving the drug for eosinophilic granulomatosis with polyangiitis or hypereosinophilic syndrome. No apparent correlation between anti-mepolizumab antibody titers and change in eosinophil concentrations. Clinical importance of such antibodies not known.

Specific Populations

Pregnancy

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

Pregnancy registry: 877-311-8972 or [Web].

Lactation

Distributed into milk in monkeys. Not known whether distributed into human milk, or has effects on the breast-fed child or milk production. Since IgG distributes into milk in humans, mepolizumab is expected to distribute into human milk.

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

Pediatric Use

Safety and efficacy for treatment of severe eosinophilic asthma not established in children <6 years of age.

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

Children with severe asthma: Safety and efficacy extrapolated from clinical studies in adults and adolescents in addition to pharmacokinetic, pharmacodynamic, and safety data in children 6–11 years of age. Dosage of 40 mg sub-Q regardless of body weight expected to result in similar exposure observed in adults and adolescents receiving 100 mg sub-Q. Safety profile and pharmacodynamics are similar to those observed in adults and adolescents ≥12 years of age.

Safety and efficacy for treatment of eosinophilic granulomatosis with polyangiitis not established in patients <18 years of age.

Safety and efficacy for treatment of hypereosinophilic syndrome established in adolescent patients ≥12 years of age. Safety and efficacy for the treatment of hypereosinophilic syndrome in pediatric patients <12 years of age not established.

Geriatric Use

Insufficient experience in patients ≥65 years of age. No overall differences in safety and efficacy 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, injection site reaction, back pain, fatigue, influenza, urinary tract infection, upper abdominal pain, pruritus, eczema, muscle spasm.

Interactions for Mepolizumab

No formal drug interaction studies to date.

Mepolizumab Pharmacokinetics

Pharmacokinetics are similar among patients with severe asthma, eosinophilic granulomatosis with polyangiitis, or hypereosinophilic syndrome.

Absorption

Bioavailability

Absolute bioavailability following sub-Q injection in patients with severe asthma approximately 80%.

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

Steady-state concentrations reached by approximately 16 weeks. Twofold accumulation of drug observed at steady state.

Dose-proportional pharmacokinetics over a sub-Q dosage range of 12.5–250 mg. Sub-Q administration of 300 mg in patients with eosinophilic granulomatosis with polyangiitis or hypereosinophilic syndrome results in approximately 3 times the systemic exposure observed in patients with severe asthma receiving 100 mg sub-Q.

Onset

Decreases in blood eosinophil count observed on the third day following sub-Q administration.

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. Exacerbation rate no different than that with placebo after 12 months.

Distribution

Extent

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

Elimination

Metabolism

Metabolized by widely distributed proteolytic enzymes.

Half-life

16–22 days.

Special Populations

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

Stability

Storage

Parenteral

Injection

Prefilled syringes and autoinjectors: 2–8°C. Keep in original carton to protect from light. Do not shake, freeze, or expose to heat. May be stored at ≤30°C in original carton for up to 7 days prior to use. Discard if not refrigerated for >7 days. Must be used within 8 hours after removal from original carton. Discard if not administered within 8 hours.

Powder for Injection

Powder: <25°C. Keep in original package and protect from light. Do not freeze.

Reconstituted solution: Use immediately or store at <30°C for up to 8 hours. Do not freeze.

Actions

Recombinant DNA-derived humanized interleukin-5 (IL-5) receptor antagonist monoclonal antibody and IgG₁ kappa immunoglobulin.
Inhibits IL-5 binding to the alpha chain of the IL-5 receptor complex expressed on the eosinophil cell surface.
Blocks IL-5 signaling that interferes with growth, differentiation, recruitment, activation, and survival of eosinophils and decreases eosinophil-mediated inflammation.
Results in dose-dependent decreases in blood eosinophil counts; effects observed 48 hours post-dose and lasting at least 8–12 weeks.

Advice to Patients

Importance of advising patients to read the manufacturer's patient information. If the patient or caregiver is administering the drug using prefilled syringes or autoinjectors, importance of advising them to read the manufacturer's instructions for use.
Risk of hypersensitivity reactions. Importance of patients informing clinicians if hypersensitivity reactions (e.g., anaphylaxis, angioedema, bronchospasm, hypotension, urticaria, rash) occur. (See Sensitivity Reactions under Cautions.)
Importance of informing patients that mepolizumab does not relieve acute asthma symptoms or exacerbations. Advise patients to contact their clinician if asthma remains uncontrolled or worsens after treatment initiation.
Possible increased risk of herpes zoster infections. Importance of patients informing clinicians if they do not have a history of varicella infection or vaccination.
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.
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 clinicians informing women about the manufacturer's pregnancy registry and encouraging patient enrollment. (See Pregnancy under Cautions.)
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.

Mepolizumab is available only through specialty pharmacies and distributors. (See Restricted Distribution under Dosage and Administration.)

Mepolizumab
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, for subcutaneous use	100 mg	Nucala	GlaxoSmithKline
	Injection, for subcutaneous use	100 mg/mL	Nucala (available as single-use prefilled syringes and single-use autoinjectors)	GlaxoSmithKline