mepolizumab
Brand: Nucala
Prototype Drug
Drug Class: biologic — anti-interleukin-5 (anti-IL-5) monoclonal antibody
Drug Family: biologic
Subclass: anti-eosinophilic biologic
Organ Systems: respiratoryimmunology
Mechanism of Action
Humanized IgG1 kappa monoclonal antibody that specifically binds to IL-5, preventing it from binding to the alpha subunit of IL-5 receptor on eosinophils; blocks IL-5-dependent eosinophil maturation, survival, and activation, reducing peripheral blood and airway eosinophil counts and eosinophilic inflammation.
interleukin-5 (IL-5)
Indications
- severe eosinophilic asthma (add-on maintenance, adults and children 6 years or older)
- eosinophilic granulomatosis with polyangiitis (EGPA)
- hypereosinophilic syndrome (HES)
Contraindications
- hypersensitivity to mepolizumab
- acute severe asthma or status asthmaticus (not rescue therapy)
Adverse Effects
Common
- injection site reactions (pain, erythema, swelling)
- headache
- back pain
- fatigue
- nasopharyngitis
Serious
- hypersensitivity reactions (anaphylaxis, urticaria)
- zoster reactivation
- helminth infections
Pharmacokinetics (ADME)
| Absorption | subcutaneous injection; bioavailability approximately 64-75%; Tmax approximately 4-8 days |
| Distribution | Vd approximately 3.6 L |
| Metabolism | proteolytic degradation to peptides and amino acids |
| Excretion | proteolytic catabolism |
| Half-life | approximately 16-22 days |
| Onset | eosinophil reduction within weeks; asthma exacerbation reduction over months |
| Peak | approximately 4-8 days post-injection |
| Duration | once every 4 weeks (monthly) |
| Protein Binding | N/A |
| Vd | approximately 3.6 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| live vaccines | potential reduction in vaccine efficacy with concurrent immunosuppression; avoid live vaccines | moderate |
Nursing Considerations
- Administer 100 mg subcutaneously once every 4 weeks; may be given in the upper arm, thigh, or abdomen; allow prefilled autoinjector to reach room temperature for 30 minutes before use.
- Observe for hypersensitivity reactions for at least 30 minutes after the first injection; epinephrine and resuscitation equipment should be readily available.
- Do not discontinue oral corticosteroids abruptly when initiating mepolizumab; gradual corticosteroid tapering under physician supervision is recommended as eosinophilic disease comes under control.
- Screen for helminth infections in patients at risk; counsel patients about zoster reactivation risk and ensure varicella zoster vaccination is up to date before initiating if possible.
Clinical Pearls
- Mepolizumab was the first anti-IL-5 agent approved for asthma (2015) and is the prototype for this drug class; it reduces severe exacerbation rates by approximately 50% and allows oral corticosteroid dose reduction in corticosteroid-dependent severe asthma.
- Patient selection requires blood eosinophil count at or above 150 cells/mcL (at baseline) or history suggesting eosinophilic asthma; patients with eosinophil counts below 150 cells/mcL generally do not respond to anti-IL-5 therapy.
Safety Profile
Pregnancy avoid
Lactation insufficient-data
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Guideline Update pending
Concordance Terms
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