EBGLYSS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EBGLYSS (EBGLYSS).
Ebglyss is a monoclonal antibody that binds to the A subunit of interleukin-13 (IL-13), blocking its interaction with the IL-13 receptor. This inhibits IL-13-mediated signaling, reducing inflammation and skin barrier dysfunction in atopic dermatitis.
| Metabolism | Ebglyss is a monoclonal antibody; it is expected to be degraded into small peptides and amino acids via catabolic pathways. No specific metabolic enzymes are involved. |
| Excretion | Primarily through biliary/fecal route (approximately 70% of absorbed dose as unchanged drug in feces), with approximately 30% renally eliminated (mostly as metabolites). Less than 5% of the administered dose is excreted unchanged in urine. |
| Half-life | Terminal elimination half-life ranges from 90 to 110 hours (~4 days). This long half-life supports weekly subcutaneous dosing; steady-state concentrations are achieved after approximately 14 weeks of weekly administration. |
| Protein binding | 99.5% bound to plasma proteins, primarily albumin. Binding is concentration-independent. |
| Volume of Distribution | Approximately 0.5 L/kg. Indicates distribution primarily within the vascular and interstitial spaces, consistent with a large protein therapeutic that does not extensively penetrate cells. |
| Bioavailability | Subcutaneous administration: approximately 72% (based on population pharmacokinetic analysis). Absolute bioavailability is high, with rapid and near-complete absorption from the injection site. |
| Onset of Action | Subcutaneous route: Clinical improvement in pruritus and sleep disturbance may be observed within 1 to 2 weeks; maximal reduction in itch scores typically seen after 4 to 6 weeks of weekly dosing. |
| Duration of Action | Duration of clinical effect for itch reduction and sleep improvement is maintained with continuous weekly subcutaneous dosing. Upon discontinuation, symptoms may return within 4 to 8 weeks. |
EBGLYSS (lebrikizumab-lbkz) is administered subcutaneously. Loading dose: 500 mg (two 250 mg injections) at week 0 and week 2. Maintenance dose: 250 mg every 2 weeks thereafter.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. For severe renal impairment (eGFR <30 mL/min/1.73 m²), use with caution; data insufficient for specific dose recommendations. |
| Liver impairment | No dose adjustment for mild hepatic impairment (Child-Pugh A). For moderate or severe hepatic impairment (Child-Pugh B or C), use is not recommended due to lack of data. |
| Pediatric use | Safety and efficacy in pediatric patients (<18 years) have not been established; no dosing recommendations available. |
| Geriatric use | No specific dose adjustment required for elderly patients (≥65 years). However, consider age-related comorbidities and potential for decreased renal function; monitor for adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EBGLYSS (EBGLYSS).
| Breastfeeding | Unknown whether lebrikizumab is excreted in human milk. Human IgG antibodies are present in breast milk, but large protein molecules are likely degraded in the infant gastrointestinal tract, with minimal systemic absorption. M/P ratio not available. Consider developmental and health benefits of breastfeeding along with maternal need for EBGLYSS and potential adverse effects on the breastfed infant. Caution recommended. |
| Teratogenic Risk | EBGLYSS (lebrikizumab) is a humanized monoclonal antibody targeting IL-13. As an IgG4 antibody, it is actively transported across the placenta during the third trimester, potentially exposing the fetus to pharmacologically active levels. Limited human data; animal studies show no evidence of fetal harm at doses up to 100 mg/kg (exposure 10-20x clinical exposure). Risk cannot be excluded; use only if benefit outweighs risk. First trimester: minimal placental transfer; second trimester: increasing transfer; third trimester: maximal transfer, potential for immunosuppression in neonate. |
■ FDA Black Box Warning
None
| Serious Effects |
["Known hypersensitivity to ebglyss or any excipient.","Severe active infection (relative)."]
| Precautions | ["Hypersensitivity reactions: including anaphylaxis, angioedema, and urticaria; discontinue if severe.","Infections: may increase risk; consider withholding treatment during serious infection.","Eosinophilic conditions: monitor for eosinophilic pneumonia or vasculitis.","Vaccinations: avoid live vaccines during treatment.","Ocular events: conjunctivitis and keratitis reported; monitor and manage appropriately."] |
| Food/Dietary | No significant food interactions. Grapefruit or other CYP inhibitors/inducers are not expected to affect lebrikizumab. |
Loading safety data…
| Fetal Monitoring | Monitor for maternal infections during pregnancy. For infants exposed in utero during third trimester, monitor for immunosuppression, including infections and response to vaccines. Assess complete blood counts and immunoglobulin levels if clinically indicated. No specific fetal monitoring required beyond standard prenatal care. |
| Fertility Effects | No human data on fertility effects. In animal studies, no adverse effects on male or female fertility were observed at doses up to 100 mg/kg (approximately 10-20 times the human exposure). EBGLYSS is not expected to impair fertility. |
| Clinical Pearls | EBGLYSS (lebrikizumab) is an IL-13 antagonist approved for moderate-to-severe atopic dermatitis. Monitor for conjunctivitis and injection site reactions. Do not administer live vaccines during treatment. Assess for parasitic infections before initiation. Renal impairment (eGFR <30 mL/min) requires dose adjustment. |
| Patient Advice | EBGLYSS is given as a subcutaneous injection every 4 weeks after a loading dose. · Common side effects include eye irritation, injection site pain, and headache. · Report any eye redness, itching, or vision changes to your doctor immediately. · Avoid receiving live vaccines while taking EBGLYSS. · Store EBGLYSS in the refrigerator at 36°F to 46°F (2°C to 8°C). Do not freeze. |