Usage
Mepolizumab is prescribed as an add-on maintenance treatment for the following conditions:
- Severe Eosinophilic Asthma: In adults, adolescents, and children aged 6 years and older.
- Chronic Rhinosinusitis with Nasal Polyps (CRSwNP): In adults with inadequate response to nasal corticosteroids.
- Eosinophilic Granulomatosis with Polyangiitis (EGPA): In adults and adolescents aged 12 years and older.
- Hypereosinophilic Syndrome (HES): In adults without an identifiable non-hematologic secondary cause.
Pharmacological Classification: Interleukin-5 (IL-5) antagonist monoclonal antibody.
Mechanism of Action: Mepolizumab binds to IL-5, a key cytokine responsible for the growth, differentiation, activation, and survival of eosinophils. By preventing IL-5 from binding to its receptor on the surface of eosinophils, mepolizumab reduces the production and survival of these cells. This leads to a decrease in eosinophil levels in the blood and tissues, mitigating inflammation and improving symptoms in eosinophilic-driven diseases.
Alternate Names
Mepolizumab is the generic name. A popular brand name is Nucala.
How It Works
Pharmacodynamics: Mepolizumab reduces blood and tissue eosinophil levels, resulting in decreased airway inflammation and improved lung function in asthma, reduced nasal polyp size in CRSwNP, and controlled organ involvement in EGPA and HES.
Pharmacokinetics:
- Absorption: Administered subcutaneously, with good bioavailability.
- Metabolism: Degraded by proteolytic enzymes found throughout the body, not specifically in the liver or kidneys.
- Elimination: Not renally or hepatically cleared. Elimination half-life is approximately 16-22 days.
Mode of Action: Binds directly to IL-5, preventing it from interacting with the IL-5 receptor alpha on the surface of eosinophils, thus inhibiting eosinophil activation and survival.
Receptor Binding: Specifically targets the IL-5 cytokine.
Elimination Pathways: Non-specific proteolytic degradation.
Dosage
Standard Dosage
Adults:
- Severe Eosinophilic Asthma, CRSwNP: 100 mg subcutaneously every 4 weeks.
- EGPA, HES: 300 mg subcutaneously every 4 weeks (administered as three separate 100 mg injections).
Children:
- Severe Eosinophilic Asthma (6-11 years): 40 mg subcutaneously every 4 weeks.
Special Cases:
- Elderly Patients: No dose adjustment is typically required.
- Patients with Renal Impairment: No dose adjustment is necessary.
- Patients with Hepatic Dysfunction: No dose adjustment is necessary.
- Patients with Comorbid Conditions: Close monitoring is advised, and dose adjustments may be necessary on a case-by-case basis.
Clinical Use Cases
Mepolizumab is not indicated for acute conditions like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. It is a maintenance treatment for chronic conditions.
Dosage Adjustments
No specific dose adjustments are recommended for renal or hepatic impairment. For other conditions, consult clinical guidelines and consider individual patient needs.
Side Effects
Common Side Effects:
- Headache
- Injection site reactions (pain, redness, itching)
- Back pain
- Fatigue
Rare but Serious Side Effects:
- Hypersensitivity reactions (anaphylaxis, angioedema, bronchospasm)
- Herpes zoster reactivation
Long-Term Effects:
Long-term effects are still being evaluated. Regular monitoring for potential complications is recommended.
Adverse Drug Reactions (ADR):
Any signs of hypersensitivity should be considered a serious ADR requiring immediate intervention.
Contraindications
- Hypersensitivity to mepolizumab or any of its excipients.
Drug Interactions
Limited data are available. Drug interactions via CYP450, efflux pumps, or protein binding are not expected. However, there is a theoretical risk of reduced efficacy with live vaccines. Consult clinical resources for updated information.
Pregnancy and Breastfeeding
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Pregnancy: Limited data available. While animal studies do not indicate reproductive toxicity, the potential risk to the fetus is unknown. Use only if the potential benefit outweighs the potential risk. A pregnancy registry is available.
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Breastfeeding: Unknown if mepolizumab is excreted in human milk. IgG is present in human milk, but the amount of mepolizumab, if any, is unknown. A shared decision between the mother and healthcare provider is needed, weighing the benefits of breastfeeding against the potential risk to the infant.
Drug Profile Summary
- Mechanism of Action: IL-5 antagonist monoclonal antibody that reduces eosinophil levels.
- Side Effects: Headache, injection site reactions, back pain, fatigue; rarely hypersensitivity.
- Contraindications: Hypersensitivity to mepolizumab.
- Drug Interactions: Limited data available; minimal drug interactions expected.
- Pregnancy & Breastfeeding: Limited data, weigh benefit vs risk.
- Dosage: Varies based on indication and age; 100 mg q4w for adults (asthma, CRSwNP); 300mg q4w for adults (EGPA, HES); 40mg q4w for children (6-11 years) with asthma.
- Monitoring Parameters: Eosinophil counts, asthma control, symptom improvement, adverse events.
Popular Combinations
Mepolizumab is often used in combination with inhaled corticosteroids in severe eosinophilic asthma. Specific combination therapies should be based on individual patient needs and clinical guidelines.
Precautions
- General Precautions: Screen for allergies and relevant medical history before initiating treatment.
- Specific Populations: As noted above, careful consideration of risks and benefits is needed for pregnant/breastfeeding women, children, and the elderly.
- Lifestyle Considerations: No specific lifestyle restrictions are typically associated with mepolizumab.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Mepolizumab?
A: The dosage depends on the indication and age. 100 mg subcutaneously every 4 weeks for adults with asthma or CRSwNP; 300 mg subcutaneously every 4 weeks for adults with EGPA or HES; 40 mg subcutaneously every 4 weeks for children aged 6-11 years with severe eosinophilic asthma.
Q2: How is Mepolizumab administered?
A: Administered via subcutaneous injection.
Q3: Can Mepolizumab be used to treat acute asthma exacerbations?
A: No, it is not indicated for acute asthma management.
Q4: What are the most common side effects?
A: Headache, injection site reactions, back pain, and fatigue.
Q5: Are there any contraindications to using Mepolizumab?
A: Known hypersensitivity to mepolizumab or its excipients is a contraindication.
Q6: Can Mepolizumab be used during pregnancy or breastfeeding?
A: Limited data available. Use only if the potential benefit outweighs the potential risk. Discuss with the patient and consult relevant clinical guidelines.
Q7: How does Mepolizumab affect eosinophils?
A: It blocks IL-5, a cytokine essential for eosinophil growth and survival, thereby reducing eosinophil levels.
Q8: How often should patients receive Mepolizumab injections?
A: Every 4 weeks.
Q9: What should be monitored in patients receiving Mepolizumab?
A: Monitor for efficacy (eosinophil counts, asthma control, symptom improvement) and adverse events, especially hypersensitivity reactions.
