ELZONRIS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ELZONRIS (ELZONRIS).
ELZONRIS is a recombinant interleukin-3 (IL-3) receptor-directed cytotoxin composed of human IL-3 and a truncated diphtheria toxin. It binds to CD123, the IL-3 receptor alpha chain, expressed on blastic plasmacytoid dendritic cell neoplasm (BPDCN) cells and some normal hematopoietic cells. After internalization, the diphtheria toxin moiety inhibits protein synthesis, leading to cell death.
| Metabolism | ELZONRIS is a protein therapeutic; metabolism is expected to involve catabolism into small peptides and amino acids via general protein degradation pathways. No specific CYP450 involvement. |
| Excretion | Eliminated primarily via proteolytic degradation; less than 1% excreted unchanged in urine. Fecal/biliary excretion not established. |
| Half-life | Approximately 27 hours at steady state for the active payload (tagraxofusp). Dosing interval is every 21 days. |
| Protein binding | Undetermined for the fusion protein; the cytotoxic payload (DM1) is 93% bound to plasma proteins. |
| Volume of Distribution | Mean Vdss is approximately 7.1 L (not weight-normalized), suggesting distribution primarily in plasma and interstitial fluid. |
| Bioavailability | Intravenous: 100%. |
| Onset of Action | Intravenous: clinical effect (reduction in blasts) observed within 1-2 weeks of first dose. |
| Duration of Action | Duration of cytotoxic effect is approximately 21 days (dosing interval). Repeated dosing required for sustained response. |
12 mcg/kg intravenously over 15 minutes once daily for 5 days in a 21-day cycle.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Safety and efficacy not established in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not recommended in moderate or severe hepatic impairment (Child-Pugh B or C) due to lack of data. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established; no approved pediatric dosing available. |
| Geriatric use | No specific dose adjustment recommended for elderly patients. Clinical studies included limited numbers of patients aged ≥65 years; no overall differences in safety or efficacy observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ELZONRIS (ELZONRIS).
| Breastfeeding | There is no information regarding the presence of tagraxofusp in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed infants from ELZONRIS, advise women not to breastfeed during treatment and for at least 1 week after the last dose. M/P ratio: Not available. |
| Teratogenic Risk | Based on its mechanism of action (interleukin-3 receptor alpha-directed cytotoxin), ELZONRIS is expected to cause fetal harm when administered to pregnant women. There are no adequate and well-controlled studies in pregnant women. In animal reproduction studies, administration of tagraxofusp to pregnant rats during organogenesis resulted in embryofetal toxicity at doses below the recommended human dose. The drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Trimester-specific risks: First trimester: Potential for teratogenicity; avoidance recommended. Second and third trimesters: Risk of fetal toxicity; use only if clearly needed. |
■ FDA Black Box Warning
Capillary leak syndrome (CLS) can occur, which may be life-threatening or fatal. Monitor for signs and symptoms of CLS, including hypotension, edema, and hypoalbuminemia.
| Serious Effects |
History of severe hypersensitivity to ELZONRIS or any components.
| Precautions | Capillary leak syndrome (CLS), hypersensitivity reactions (including anaphylaxis), hepatotoxicity, infection risk, leukopenia, neutropenia, lymphopenia, thrombocytopenia. |
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| Fetal Monitoring | Monitor pregnant women for signs of capillary leak syndrome (CLS), including hypotension, hypoalbuminemia, edema, and weight gain. Monitor hepatic function (ALT, AST, bilirubin), serum albumin, and vital signs. Perform complete blood counts and assess for infections. Fetal monitoring should include standard prenatal care, including ultrasound for fetal growth and amniotic fluid volume if clinically indicated. |
| Fertility Effects | Based on animal studies, ELZONRIS may impair fertility in females and males. In rats, tagraxofusp caused decreased fertility indices and increased pre- and post-implantation loss. The effects on human fertility are unknown. |