Drug information of mepolizumab

Mechanism of effect

Humanized IgG1 kappa monoclonal antibody specific for IL-5; binds IL-5, and therefore stops IL-5 from binding to its receptor on the surface of eosinophils

Inhibiting IL-5 binding to eosinophils reduces blood, tissue, and sputum eosinophil levels

Pharmacodynamic

Mepolizumab is a monoclonal antibody that acts through interleukin-5 (IL-5) antagonism to reduce blood eosinophil levels, generally in the range of 60-90% of baseline depending on dose, which in turn offers therapeutic benefit in the specific conditions for which mepolizumab is indicated. Mepolizumab has a relatively long half-life of between 16 and 22 days, which allows for long-lasting therapeutic benefit and a four-week dosing schedule. Despite a good demonstrated safety profile, mepolizumab use does act to depress part of the immune system and may be associated with increased infections, such as with herpes zoster virus; pre-existing helminth infections should be treated before starting mepolizumab therapy. Inhaled and oral corticosteroids should not be discontinued after starting mepolizumab but may be tapered as appropriate. Mepolizumab should not be used to treat acute bronchospasms or status asthmatics. Finally, hypersensitivity reactions, including anaphylaxis, have been reported in patients; mepolizumab should be discontinued in patients with suspected or confirmed hypersensitivity.

Pharmacokinetics

Absorption

Bioavailability: 80%

Following repeat SC administration once every 4 weeks, there was ~2-fold accumulation at steady-state

Distribution

Vd: 3.6 L (70-kg adult)

Metabolism

Degraded by proteolytic enzymes widely distributed in the body and not restricted to hepatic tissue

Elimination

Half-life: 16-22 days

Systemic clearance: 0.28 L/day (70-kg adult)

Drug indications

Asthma , Asthma - Maintenance

Dosage

Severe Asthma

Indicated for add-on maintenance treatment of severe asthma in patients with an eosinophilic phenotype

100 mg SC q4wk

Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome)

Indicated for adults with eosinophilic granulomatosis with polyangiitis (EGPA)

300 mg SC q4wk (ie, as 3 separate 100-mg SC injections)

Hypereosinophilic Syndrome

Indicated for adults and pediatric patients aged ≥12 years with hypereosinophilic syndrome (HES) for 6 months without an identifiable nonhematologic secondary cause

300 mg SC q4wk (ie, as 3 separate 100-mg SC injections)

Drug contraindications

Hypersensitivity to this drug

Side effects

Pain , Headache , vertigo , Urinary tract infection , respiratory tract infection , Injection-site reaction , itching , eczema , tiredness , Abdominal pains , shortness of breath , allergic reactions , stuffy nose , Allergic Rhinitis

Interactions

Benralizumab , RESLIZUMAB , alirocumab

Alerts

Hypersensitivity reactions (eg, angioedema, bronchospasm, hypotension, urticaria, rash) reported; these reactions generally occur within hours of administration, but in some instances can have a delayed onset (ie, days); discontinue drug in the event of a hypersensitivity reaction

Not for treatment of acute asthma symptoms or acute exacerbations; do not use to treat acute bronchospasm or status asthmaticus; instruct patients to seek immediate medical advice if their asthma remains uncontrolled or worsens after initiating mepolizumab

In clinical trials, 2 serious adverse reactions of herpes zoster occurred during treatment compared with none in placebo; consider varicella vaccination if medically appropriate before initiating treatment

Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation mepolizumab; 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

Eosinophils may be involved in the immunological response to some helminth infections; patients with known parasitic infections were excluded from participation in clinical trials; treat patients with preexisting helminth infection before initiating mepolizumab; if helminth infection occurs while receiving mepolizumab that does not respond to treatment, discontinue mepolizumab until the infection resolves

Points of recommendation

SC Preparation

Lyophilized powder for reconstitution

• Reconstitute each vial with 1.2 mL sterile water for injection (SWI); reconstituted solution yields a concentration of 100 mg/mL
• Preparation of the 300-mg dose for treatment of EGPA requires the reconstitution of 3 separate 100-mg vials
• Do not mix with other medications
• Direct the stream of SWI vertically onto the center of the lyophilized cake
• Gently swirl vial for 10 sec with a circular motion at 15-sec intervals until powder dissolves
• Reconstitution is typically complete within 5 min after the SWI has been added, but it may take additional time
• If a mechanical reconstitution device (swirler) is used, swirl at 450 rpm for ≤10 min; alternatively, may swirl at 1000 rpm for ≤5 min
• Visually inspect for particulate matter and clarity before use
• Solution should be clear to opalescent and colorless to pale yellow or pale brown, essentially particle free; small air bubbles, however, are expected and acceptable
• Discard solution if particulate matter remains in the solution or if solution appears cloudy or milky

Prefilled autoinjector or syringe

• Remove from refrigerator and allow to sit at room temperature for ~30 min before administration; do not warm in any other way
• Visually inspect window of autoinjector or syringe for particulate matter or discoloration
• Solution should be clear-to-opalescent, colorless-to-pale yellow or pale brown in color
• Do not use if solution appears discolored, cloudy, or has particulate matte
• Do not use if dropped on a hard surface

SC Administration

Do NOT shake reconstituted solution; gently swirl to avoid foaming or precipitation

For SC use only

Administer SC into the upper arm, thigh, or abdomen

Asthma

• 40-mg dose: Remove 0.4 mL of reconstituted solution; administer 0.4 mL (equivalent to 40-mg dose)
• 100-mg dose: Remove 1 mL of reconstituted solution; administer 1 mL (equivalent to 100-mg dose)

EGPA

• 300-mg dose: Administer as 3 separate 100-mg injections; individual 100-mg injections should be administered at least 5-cm (~2-inches) apart if administered at the same site

Missed dose

• Administer as soon as possible; thereafter, resume dosing on usual day of administration; if next dose is due, then administer as scheduled

Storage

Lyophilized powder

• Store below 25°C (77°F)
• Do not freeze
• Store in the original package to protect from light

Reconstituted solution

• Store below 30°C (86°F)
• Do not freeze
• Discard if not used within 8 hr of reconstitution

Autoinjector or prefilled syringe

• Before or after dispensing

  • Refrigerate at 36-46°F (2-8°C)
  • Keep in the original carton to protect from light
  • Do not freeze
  • Do not shake
  • Avoid exposure to heat
  • If necessary, unopened carton can be stored outside refrigerator at up to 86°F (30°C) for up to 7 days
  • Discard if left out of refrigerator >7 days
  • Must be administered within 8 hr after removal from carton; discard if not administered within 8 hr

Pregnancy level

HAVE NOT BEEN ESTABLISHED

Data on pregnancy exposure from the clinical trials are insufficient to inform on drug-associated risk

Monoclonal antibodies, such as mepolizumab, are transported across the placenta in a linear fashion as pregnancy progresses; therefore, potential effects on a fetus are likely to be greater during the second and third trimesters of pregnancy

Breast feeding warning

Unknown if distributed in human breast milk

However, mepolizumab is a humanized monoclonal antibody (IgG1 kappa), and immunoglobulin G (IgG) is present in human milk in small amounts

Present in the milk of cynomolgus monkeys postpartum following dosing during pregnancy; levels in milk were ≤0.5% of maternal serum concentration

Consider developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Related drugs

Benralizumab , RESLIZUMAB , secukinumab , Sarilumab , Dupilumab , Risankizumab , Tildrakizumab , Guselkumab , Brodalumab , Ustekinumab , sirukumab , mepolizumab , ixekizumab

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