NUCALA
Clinical safety rating
cautionComprehensive clinical and safety monograph for NUCALA (NUCALA).
Comprehensive clinical and safety monograph for NUCALA (NUCALA).
Add-on maintenance treatment of severe asthma with an eosinophilic phenotypeMaintenance treatment of eosinophilic granulomatosis with polyangiitis (EGPA)Treatment of hypereosinophilic syndrome (HES) for ≥6 months without an identifiable non-hematologic secondary cause
Headache, Injection site reactions (pain, swelling, redness), Back pain, Fatigue
Mepolizumab is an interleukin-5 (IL-5) antagonist monoclonal antibody. It binds to IL-5 with high affinity, preventing IL-5 from binding to its receptor on eosinophils. This inhibits IL-5-mediated signaling, reducing the production and survival of eosinophils and leading to decreased eosinophil levels in blood and tissues.
| Metabolism | Mepolizumab is a humanized monoclonal antibody of the IgG1/kappa subclass. As a protein, it is expected to be degraded into small peptides and amino acids via general catabolic pathways. It does not undergo hepatic metabolism via CYP450 enzymes. |
| Excretion | Primarily degraded into small peptides and amino acids via general protein catabolism; <1% excreted unchanged in urine; no significant biliary or fecal elimination. |
| Half-life | Terminal half-life approximately 16 days (range 10–20 days); supports monthly subcutaneous dosing regimen. |
| Protein binding | Approximately 99% bound to plasma proteins (likely endogenous IgG4 and other immunoglobulins). |
| Volume of Distribution | Approximately 0.06 L/kg (central volume); low Vd consistent with limited extravascular distribution of a monoclonal antibody. |
| Bioavailability | Subcutaneous: approximately 74% (based on population pharmacokinetic analysis). |
| Onset of Action | Subcutaneous: Reduction in eosinophil count observed within 24 hours; clinical improvement in asthma symptoms may be evident within 4–8 weeks. |
| Duration of Action | Pharmacodynamic effect on eosinophils persists for up to 20 weeks after last dose; clinical duration of asthma control with continued monthly dosing; no tachyphylaxis reported. |
| Molecular Weight | 149000 Da |
100 mg subcutaneously once every 4 weeks for severe eosinophilic asthma; 100 mg subcutaneously once every 4 weeks for chronic rhinosinusitis with nasal polyps; 3 mg/kg (max 300 mg) intravenously every 4 weeks for eosinophilic granulomatosis with polyangiitis; 3 mg/kg (max 300 mg) intravenously every 4 weeks for hypereosinophilic syndrome.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment recommended per manufacturer; studies not conducted in renal impairment. |
| Liver impairment | No dose adjustment recommended per manufacturer; mild to moderate hepatic impairment: no data; severe hepatic impairment: not studied. |
| Pediatric use | Age 6-11 years: 40 mg subcutaneously once every 4 weeks for severe eosinophilic asthma; age 12-17 years: 100 mg subcutaneously once every 4 weeks. |
| Geriatric use | No specific dose adjustment; limited data in patients ≥65 years; caution advised due to potential for greater sensitivity. |
| 1st trimester | Limited human data; use only if clearly needed. |
| 2nd trimester | Limited human data; use only if clearly needed. |
| 3rd trimester | Limited human data; use only if clearly needed. |
Clinical note
Comprehensive clinical and safety monograph for NUCALA (NUCALA).
| Placental transfer | IgG monoclonal antibodies cross placenta; extent unknown. |
| Breastfeeding | Not known if excreted in human milk; consider developmental benefits of breastfeeding alongside maternal need for drug. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | NUCALA (mepolizumab) is a humanized monoclonal antibody (IgG1) that targets IL-5. IgG antibodies are actively transported across the placenta, predominantly during the third trimester. Limited human data; animal studies showed no evidence of fetal harm at doses up to 100 mg/kg SC (approximately 20 times the MRHD based on AUC). No known teratogenic effects. First trimester: minimal transfer; second trimester: increasing transfer; third trimester: highest transfer. Fetal risks cannot be ruled out; use only if clearly needed. |
| Fetal Monitoring | For pregnant women: monitor for maternal infections. For neonates: monitor for potential immunosuppression (e.g., infections) if exposed in utero during third trimester. No specific fetal monitoring required beyond routine prenatal care. |
| Fertility Effects | No human data on fertility impairment. Animal studies: no adverse effects on male or female fertility at doses up to 100 mg/kg SC (approximately 20 times the MRHD). |
■ FDA Black Box Warning
No black box warning.
| Serious Effects |
Hypersensitivity to mepolizumab or excipients
| Precautions | Hypersensitivity reactions (e.g., angioedema, bronchospasm, hypotension, urticaria, rash) can occur; discontinue if severe, Acute asthma symptoms or exacerbations: Do not use for acute bronchospasm or status asthmaticus, Herpes zoster infection: Consider vaccination if appropriate |
| Food/Dietary | No clinically significant food interactions reported. NUCALA can be administered without regard to meals. |
| Clinical Pearls | NUCALA (mepolizumab) is an anti-IL-5 monoclonal antibody. Monitor for hypersensitivity reactions, including angioedema, bronchospasm, and urticaria. Do not use for acute asthma exacerbations. Assess for pre-existing helminth infections before initiation; treat if present. Injection site reactions (pain, erythema, swelling) are common; rotate injection sites. Consider periodic blood counts as eosinophilia may recur upon discontinuation. Efficacy in eosinophilic granulomatosis with polyangiitis (EGPA) may require concomitant corticosteroid tapering under specialist guidance. |
| Patient Advice | NUCALA is not a rescue medication for sudden asthma attacks; always carry your rescue inhaler. · Report any signs of allergic reaction such as hives, swelling, or difficulty breathing immediately. · Tell your doctor if you have a parasitic infection or live in an area with high helminth risk. · Store NUCALA in the refrigerator at 2°C to 8°C, protect from light, and do not freeze. · Administer the injection subcutaneously into the thigh, abdomen, or upper arm; rotate sites. · Do not stop taking other asthma medications unless instructed by your doctor. · Common side effects include headache, injection site reactions, and back pain. · Inform your healthcare provider if you are pregnant, planning to become pregnant, or breastfeeding. |
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