tezepelumab
Brand: Tezspire
Prototype Drug
Drug Class: biologic — anti-thymic stromal lymphopoietin (anti-TSLP) monoclonal antibody
Drug Family: biologic
Subclass: epithelial cytokine inhibitor — upstream biologic for asthma
Organ Systems: respiratoryimmunology
Mechanism of Action
Fully human IgG2 lambda monoclonal antibody that binds TSLP, an epithelial cytokine released in response to allergens, pollutants, and infectious triggers; TSLP blockade prevents downstream activation of dendritic cells, innate lymphoid cells, mast cells, basophils, and eosinophils, suppressing all major inflammatory pathways in asthma regardless of phenotype.
thymic stromal lymphopoietin (TSLP)
Indications
- severe uncontrolled asthma as add-on maintenance therapy (adults and adolescents 12 years and older)
- effective in eosinophilic and non-eosinophilic asthma phenotypes
Contraindications
- hypersensitivity to tezepelumab
- acute asthma exacerbation (not rescue therapy)
Adverse Effects
Common
- pharyngitis
- arthralgia
- injection site reactions
- back pain
Serious
- hypersensitivity reactions (rare)
- helminth infections (theoretical based on mechanism)
Pharmacokinetics (ADME)
| Absorption | subcutaneous injection; bioavailability approximately 77%; Tmax approximately 3-10 days |
| Distribution | Vd approximately 4.5 L |
| Metabolism | proteolytic degradation to amino acids |
| Excretion | proteolytic catabolism |
| Half-life | approximately 26 days |
| Onset | clinical exacerbation reduction over weeks to months |
| Peak | approximately 3-10 days |
| Duration | once every 4 weeks subcutaneous injection |
| Protein Binding | N/A |
| Vd | approximately 4.5 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| live vaccines | potential immune interference; avoid live vaccines | moderate |
Nursing Considerations
- Administer 210 mg subcutaneously every 4 weeks; allow to reach room temperature for 30 minutes before administration; inject in abdomen, thigh, or upper arm with rotation of sites.
- Unlike anti-IL-5 biologics, tezepelumab does not require baseline blood eosinophil count to predict response; it is effective across all asthma inflammatory phenotypes including non-eosinophilic asthma.
- Observe patients for hypersensitivity reactions after administration; symptoms typically occur within hours of injection; ensure epinephrine is accessible.
- Emphasize that tezepelumab is an add-on maintenance medication and does not replace ICS, LABA, or rescue SABA; instruct patients on the continuing need for rescue therapy.
Clinical Pearls
- Tezepelumab is the first FDA-approved biologic that targets TSLP, an upstream 'master switch' cytokine; by blocking the initial epithelial alarm signal, it reduces multiple downstream inflammatory cascades simultaneously — including eosinophilic, Th2, and non-Th2 pathways.
- Unlike anti-IL-5 agents (mepolizumab, benralizumab, reslizumab) which require eosinophilic phenotype for efficacy, tezepelumab demonstrated significant exacerbation reduction in patients with low eosinophil counts — expanding the eligible population to non-eosinophilic asthma.
Safety Profile
Pregnancy avoid
Lactation insufficient-data
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Guideline Update pending
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.