Elzonris (tagraxofusp-erzs)
Antineoplastic - CD123-Directed Cytotoxin Conjugate Intravenous Vial (Ml)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Tagraxofusp, a CD123-directed fusion protein consisting of recombinant human interleukin-3 (IL-3) linked to truncated diphtheria toxin, is an antineoplastic agent.
Tagraxofusp, a CD123-directed fusion protein consisting of recombinant human interleukin-3 (IL-3) linked to truncated diphtheria toxin, is an antineoplastic agent. The drug is produced by recombinant DNA technology in Escherichia coli cells. Tagraxofusp is a fusion protein designed to direct the cytocidal activity of diphtheria toxin to cells that express the IL-3 receptor, a cytokine overexpressed in certain hematologic malignancies (i.e., acute myeloid leukemia, myelodysplastic syndrome, chronic myeloid leukemia, acute lymphocytic leukemia, hairy cell leukemia, myeloproliferative neoplasms, blastic plasmacytoid dendritic cell neoplasm) relative to normal cells.
The IL-3 portion of tagraxofusp binds specifically to IL-3 receptor alpha-chain (IL-3R alpha; also known as CD123). Following binding of tagraxofusp to CD123-expressing cells, the resultant complex is internalized by the cell. Truncated and catalytic domains of the diphtheria toxin are released into cytosol and inactivate adenosine diphosphate (ADP)-ribosylation of elongation factor 2 causing inhibition of protein synthesis and subsequent apoptosis.
Following administration of tagraxofusp-erzs 12 mcg/kg by IV infusion over 15 minutes, area under the concentration-time curve (AUC) and peak plasma concentration of the drug were reduced by 34.6 and 50.6%, respectively, and clearance of the drug was increased by 1.96-fold in patients with preexisting anti-tagraxofusp antibodies compared with patients without anti-tagraxofusp antibodies at baseline; however, no dosage adjustment is necessary in such patients. The mean terminal half-life of tagraxofusp is 0.7 hours.
Pharmacokinetics of tagraxofusp does not appear to be affected by age (range: 22-84 years), sex, or body weight.
Generic name: tagraxofusp-erzs
Drug class: Antineoplastic - CD123-Directed Cytotoxin Conjugate
Therapeutic class: Antineoplastics
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Elzonris
Indications
The following indications are listed for Elzonris:
- Blastic Plasmacytoid Dendritic Cell Neoplasm
Also known as: Blastic Natural Killer Cell Leukemia, Blastic Natural Killer Cell Lymphoma.
Dosing
No dosing information is available for this tab.
Tagraxofusp-erzs is administered by IV infusion over 15 minutes using a controlled-infusion device (i.e., syringe pump). To ensure complete administration of tagraxofusp-erzs, the infusion set should be flushed with at least 3 mL of 0.9% sodium chloride injection over 15 minutes using a syringe pump.
Unopened vials of tagraxofusp-erzs injection concentrate should be stored at -25 to -15degreesC and retained in the original carton for protection from light.
Tagraxofusp-erzs injection concentrate must be diluted prior to IV administration. Prior to dilution, frozen tagraxofusp-erzs injection concentrate must be completely thawed at room temperature (15-25degreesC) for 15-30 minutes in the original carton; heat sources other than ambient air temperature should not be used. Once thawed, the injection concentrate may be stored at room temperature for approximately 1 hour prior to dilution; the injection concentrate should not be refrozen. Tagraxofusp-erzs injection concentrate and diluted solutions of the drug should be inspected visually for particulate matter and discoloration prior to dilution and administration. Thawed tagraxofusp-erzs injection concentrate should be clear and colorless; the solution may contain a few white to translucent particulates.
Based on the indicated dose of tagraxofusp-erzs, the appropriate number of vials of the drug should be thawed and diluted. Prior to dilution of the injection concentrate, vial(s) labeled as containing 1000 mcg/mL of tagraxofusp-erzs should be gently swirled. Tagraxofusp-erzs injection concentrate is diluted by adding 9 mL of 0.9% sodium chloride injection followed by 1 mL of tagraxofusp-erzs injection concentrate (containing 1000 mcg/mL) into an empty sterile 10-mL vial to achieve a final concentration of 100 mcg/mL. The diluted solution for infusion should be gently inverted at least 3 times and should not be shaken. An appropriate dose of diluted tagraxofusp-erzs solution should be withdrawn from the vial into a new sterile syringe affixed with a product label. A 0.9% sodium chloride flush label should be affixed to a separate syringe containing at least 3 mL of 0.9% sodium chloride injection.
The manufacturer's labeling should be consulted for detailed information on infusion system requirements (e.g., components, set-up) and procedures for IV infusion of tagraxofusp-erzs.
The diluted solution may be infused immediately or stored at room temperature and used within 4 hours of completing dose preparation. Any partially used vials should be discarded.
| Drug label | Dosing type | Instructions |
|---|---|---|
| Elzonris 1,000 Mcg/Ml Vial | Maintenance | Infuse 12 mcg/kg over 15 minute(s) by intravenous route once daily ondays 1 through 5 of a 21 day treatment cycle. |
No dosing information is available for this tab.
Drug interactions
No formal drug interaction studies have been performed to date. Tagraxofusp is not expected to be metabolized by cytochrome P-450 (CYP) isoenzymes. The drug also is not expected to be a substrate of metabolic transporters.
There are no contraindication interactions for this drug.
Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
Myelosuppressives; Immunomodulators/Sodium Iodide I 131
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1)
CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1)
DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1)
There are no moderate interactions for this drug.
Contraindications
The manufacturer states that there are no known contraindications to the use of tagraxofusp-erzs.
- Lactation
- Bradycardia
- Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
- Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
- Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
- Chronic kidney disease stage 5 (failure) GFr<15 ml/min
- Fever
- Hypoalbuminemia
- Pregnancy
- Tachycardia
- Kidney disease with reduction in glomerular filtration rate (GFr)
Adverse reactions
Adverse effects reported in 30% or more of patients receiving tagraxofusp-erzs include capillary leak syndrome, nausea, fatigue, peripheral edema, pyrexia, and weight gain. Laboratory abnormalities reported in 50% or more of patients receiving tagraxofusp-erzs include decreased concentrations of albumin, decreased platelet concentrations, decreased concentrations of hemoglobin, decreased concentrations of calcium, decreased concentrations of sodium, elevated concentrations of glucose, and elevated concentrations of aminotransferases (i.e., AST, ALT).
More Frequent
- Capillary leak syndrome
- Hypoalbuminemia
- Hyponatremia
- Increased alanine transaminase
- Increased aspartate transaminase
- Thrombocytopenic disorder
Less Frequent
- Hypersensitivity drug reaction
- Hypertension
- Hypotension
- Neutropenic disorder
- Tachycardia
More Frequent
- Fatigue
- Fever
- Hyperglycemia
- Hypocalcemia
- Nausea
- Peripheral edema
- Weight gain
Less Frequent
- Acute cognitive impairment
- Anorexia
- Back pain
- Chills
- Constipation
- Cough
- Diarrhea
- Dizziness
- Dyspnea
- Edema
- Epistaxis
- Headache disorder
- Hematuria
- Insomnia
- Pain
- Pain in oropharynx
- Petechiae
- Pruritus of skin
- Skin rash
- Stomatitis
- Symptoms of anxiety
- Vomiting
- Wheezing
Precautions
No enhanced messaging available.
Safety and efficacy of tagraxofusp have not been established in pediatric patients younger than 2 years of age.
Safety and efficacy of tagraxofusp for the treatment of blastic plasmacytoid dendritic cell neoplasm in pediatric patients are supported by extrapolation of data from the principal efficacy study (STML-401-0114) evaluating tagraxofusp-erzs in adults. Limited data in 3 pediatric patients (range: 2 years to less than 17 years of age) receiving tagraxofusp-erzs at the recommended dosage indicate that adverse effects in pediatric patients are similar to those reported in adults.
Tagraxofusp may cause fetal harm if administered to pregnant women based on its mechanism of action.
Pregnancy should be avoided during tagraxofusp therapy. The manufacturer states that a pregnancy test should be performed within 7 days prior to initiation of tagraxofusp therapy in females of reproductive potential and that such females should be advised to use effective contraceptive methods while receiving tagraxofusp and for at least 1 week after the last dose. If tagraxofusp is used during pregnancy, the patient should be apprised of the potential fetal hazard.
It is not known whether tagraxofusp distributes into milk in humans or whether the drug has any effects on nursing infants or on milk production. Because of the potential for serious adverse reactions to tagraxofusp in nursing infants, women should be advised to discontinue nursing during tagraxofusp therapy and for 1 week after the last dose.
In the STML-401-0114 study evaluating tagraxofusp-erzs in patients with blastic plasmacytoid dendritic cell neoplasm, 23% of patients receiving the recommended dosage of the drug were 75 years of age or older. Adverse CNS effects (i.e., confusion, delirium, mental status changes, dementia, encephalopathy) occurred more frequently in geriatric patients.
Population pharmacokinetic analysis suggests that age (range: 22-84 years) has no effect on the pharmacokinetics of tagraxofusp.
ICD codes
| Code | Type | Description |
|---|---|---|
| Blastic plasmacytoid dendritic cell neoplasm | ||
| C86.4 | ICD10CM | Blastic Nk-cell lymphoma |
ICD code information from First Databank (FDB).
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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