NUCALA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NUCALA (NUCALA).
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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NUCALA (NUCALA).
| Breastfeeding | Mepolizumab is detected in human milk at low levels. The M/P ratio is unknown. Expected to be present in milk due to IgG1 monoclonal antibody; likely degraded in infant GI tract with limited systemic absorption. No reports of adverse effects in breastfed infants. Consider benefits of breastfeeding and maternal need for NUCALA. |
| 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. |
■ FDA Black Box Warning
No black box warning.
| Serious Effects |
["Known hypersensitivity to mepolizumab or any of its 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"] |
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| 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). |