Version May 2024
Capillary leak syndrome (CLS) which may be life-threatening or fatal, can occur in patients receiving tagraxofusp. Monitor for signs and symptoms of CLS and take actions as recommended.
Note: Prior to first dose of first cycle, verify serum albumin ≥3.2 g/dL and patient has adequate cardiac function. Administer the first cycle of doses in an inpatient setting; subsequent cycles may be administered in an inpatient setting or an ambulatory outpatient setting equipped with monitoring capabilities for patients with hematopoietic malignancies. Premedicate 60 minutes prior to each infusion with an H1- and H2-histamine antagonist, corticosteroid (eg, methylprednisolone IV), and acetaminophen.
Blastic plasmacytoid dendritic cell neoplasm (BPDCN): Note: Approval in pediatric patients based on extrapolation of experience in adult patients and pediatric safety (Cuglievan 2023; Sun 2018). Dosing should be based on patient's actual body weight.
Children ≥2 years and Adolescents: IV: 12 mcg/kg/dose once daily on days 1 to 5 of a 21-day cycle; dosing period may be extended to delays up to day 10 of the 21-day cycle. Continue treatment until disease progression or unacceptable toxicity.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity: Children ≥2 years and Adolescents: IV: Data is scant in pediatric patients; use appropriate age-related parameters for children. Monitor vital signs and obtain serum albumin, transaminases, and creatinine prior to preparing each tagraxofusp dose.
Significantly low or high systolic blood pressure (SBP) (eg, in adults SBP ≤80 mm Hg or ≥160 mm Hg): Withhold therapy until SBP returns to normal (eg, in adults to >80 mm Hg or <160 mm Hg).
Significantly low or high heart rate (HR) (eg, in adults HR ≤40 bpm or ≥130 bpm): Withhold therapy until HR returns to normal (eg, in adults to >40 bpm or <130 bpm).
Body temperature ≥38°C: Withhold therapy until body temperature <38°C.
Hypersensitivity reactions:
Mild to moderate: Withhold therapy until resolution of symptoms; resume therapy at the same infusion rate.
Severe or life-threatening: Discontinue permanently.
Capillary leak syndrome (CLS): Note: Data is scant in pediatric patients (minimum reported age: 10 years) (Sun 2018); smaller pediatric patients may require dosing adjustment at different parameters (eg, changes in body weight) or symptoms:
Serum albumin <3.5 g/dL: Interrupt therapy; administer IV albumin until serum albumin raised serum albumin to ≥3.5 g/dL and not more than 0.5 g/dL lower than baseline albumin of the current cycle. Resume therapy upon resolution (see following Note).
Predose body weight increase (eg, ≥1.5 kg in adult patients) over previous day's predose weight: Interrupt therapy; administer IV albumin and manage fluid status as applicable until body weight increases have resolved (eg, in adults, any predose body weight increase is <1.5 kg from previous day's predose weight). Resume therapy upon resolution (see following Note).
Edema, fluid overload and/or hypotension: Interrupt therapy; administer IV albumin until serum albumin ≥3.5 g/dL, administer IV methylprednisolone (or equivalent), and aggressively manage fluid status/BP as necessary. Resume therapy upon resolution.
Note: When resuming therapy, may resume with the same cycle if any hemodynamic instability did not require interventions to treat; therapy should be withheld for the remainder of a cycle if signs/symptoms of CLS are unresolved or interventions were required to treat hemodynamic instability (even if resolved), and therapy may resume with the next cycle if all CLS signs/symptoms have resolved and hemodynamically stable.
Children ≥2 years and Adolescents:
Baseline (prior to initiation of therapy):
eGFR 30 to 89 mL/minute/1.73 m2: Pediatric-specific data is lacking; in adults (22 to 84 years of age), no pharmacokinetic differences were reported; no dosing adjustment necessary.
eGFR 15 to 29 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling; has not been studied.
Nephrotoxicity during therapy: SCr >1.8 mg/dL or CrCl ≤60 mL/minute: Withhold therapy until SCr ≤1.8 mg/dL or CrCl ≥60 mL/minute.
Children ≥2 years and Adolescents:
Baseline (prior to therapy initiation):
Mild hepatic impairment (total bilirubin ≤ ULN and AST > ULN, or total bilirubin 1 to 1.5 times ULN and any AST) or moderate hepatic impairment (total bilirubin >1.5 to 3 times ULN and any AST): Pediatric-specific data is lacking; in adults (22 to 84 years of age), no pharmacokinetic differences were reported; no dosing adjustment necessary.
Severe hepatic impairment (total bilirubin >3 times ULN and any AST): There are no dosage adjustments provided in the manufacturer's labeling; has not been studied.
Hepatotoxicity during therapy: ALT or AST increase >5 times ULN: Withhold therapy until transaminase elevations are ≤2.5 times ULN.
(For additional information see "Tagraxofusp: Drug information")
Note: Ensure adequate cardiac function prior to tagraxofusp initiation. Serum albumin should be ≥3.2 g/dL prior the first dose of cycle 1; monitor serum albumin levels prior to each dose and as clinically necessary. Premedicate with an H1-antagonist (eg, diphenhydramine), an H2-antagonist (eg, famotidine), a corticosteroid (eg, 50 mg IV methylprednisolone or equivalent), and acetaminophen ~60 minutes prior to each tagraxofusp infusion.
Blastic plasmacytoid dendritic cell neoplasm: IV: 12 mcg/kg (based on actual body weight) once daily on days 1 to 5 of a 21-day cycle; continue until disease progression or unacceptable toxicity (Pemmaraju 2019, Pemmaraju 2022, manufacturer’s labeling). The dosing period may be extended for dose delays up to day 10 of the cycle.
Administer cycle 1 in the inpatient setting; observe patients through at least 24 hours after the last infusion. Subsequent cycles may be administered either inpatient or outpatient (if suitable); ensure appropriate monitoring is available and observe patients for a minimum of 4 hours following each infusion.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Kidney impairment prior to therapy initiation: Kidney function at baseline estimated by the MDRD formula.
eGFR 30 to 89 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant differences in tagraxofusp pharmacokinetics were observed in patients with mild or moderate kidney impairment.
eGFR 15 to 29 mL/minute/1.73 m2: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
Kidney toxicity during treatment:
Serum creatinine >1.8 mg/dL or CrCl <60 mL/minute: Withhold tagraxofusp until serum creatinine is ≤1.8 mg/dL or CrCl is ≥60 mL/minute.
Hepatic impairment prior to therapy initiation:
Mild (total bilirubin ≤ ULN and AST > ULN or total bilirubin 1 to 1.5 times ULN and any AST) or moderate (total bilirubin >1.5 to 3 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer’s labeling; however, no clinically significant differences in tagraxofusp pharmacokinetics were observed in patients with mild or moderate hepatic impairment.
Severe (total bilirubin >3 times ULN and any AST) impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Hepatotoxicity during treatment:
AST or ALT >5 times ULN: Withhold tagraxofusp until AST and/or ALT are ≤2.5 times ULN.
Serum albumin reductions: Refer to Dosage Adjustment for Toxicity
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Cardiovascular: Capillary leak syndrome (53%), hypertension (14%), hypotension (25%), peripheral edema (39%), tachycardia (17%)
Endocrine & metabolic: Decreased serum albumin (72%), decreased serum calcium (57%), decreased serum magnesium (25%), decreased serum phosphate (32%), decreased serum potassium (36%), decreased serum sodium (52%), hypermagnesemia (13%), increased serum glucose (89%), increased serum potassium (20%), weight gain (31%)
Gastrointestinal: Constipation (24%), decreased appetite (22%), diarrhea (21%), nausea (45%), vomiting (19%)
Hematologic & oncologic: Decreased hemoglobin (61%; grades ≥3: 30%), decreased neutrophils (38%; grades ≥3: 29%), decreased platelet count (68%; grades ≥3: 49%), febrile neutropenia (19%; grades ≥3: 16%)
Hepatic: Increased serum alanine aminotransferase (79%), increased serum alkaline phosphatase (22%), increased serum aspartate aminotransferase (76%), increased serum bilirubin (11%)
Hypersensitivity: Hypersensitivity reaction (43%)
Immunologic: Antibody development (68% to 99%; neutralizing: 85%)
Nervous system: Anxiety (15%), chills (26%), dizziness (21%), fatigue (45%), headache (28%), insomnia (16%)
Neuromuscular & skeletal: Back pain (19%)
Renal: Increased serum creatinine (26%)
Respiratory: Cough (12%), dyspnea (20%), epistaxis (12%)
Miscellaneous: Fever (43%)
1% to 10%:
Dermatologic: Pruritus (10%)
Endocrine & metabolic: Decreased serum glucose (10%)
Hematologic & oncologic: Tumor lysis syndrome (<10%)
Neuromuscular & skeletal: Limb pain (10%)
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Capillary leak syndrome: In clinical trials, capillary leak syndrome (CLS), including life-threatening and fatal cases, was observed in over half of patients; approximately half of CLS events were grade 1 or 2; grades 3 and 4 CLS events have also been reported. The median time to onset was 4 days (range: 1 to 46 days) with most patients experiencing an event during the first cycle. Signs and symptoms of tagraxofusp-associated CLS include hypoalbuminemia, edema, weight gain, and hypotension.
• Hepatotoxicity: Hepatic transaminase elevations (ALT, AST) have been reported in close to 80% of patients. Grade 3 toxicity occurred in approximately one-third of patients; grade 4 elevations were also reported. Hepatic transaminase elevations occurred mainly during the first cycle of therapy and were reversible upon therapy interruption.
• Hypersensitivity: Severe hypersensitivity reactions may occur. In clinical trials, hypersensitivity reactions occurred in close to half of patients; 10% of events were ≥ grade 3. Reactions included rash, pruritus, stomatitis, and wheezing.
Special populations:
• Older adult: Patients ≥75 years experienced a higher incidence of altered mental status (eg, confusion, delirium, mental status changes, dementia, encephalopathy) compared to patients <75 years of age.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Elzonris: Tagraxofusp-erzs 1000 mcg/mL (1 mL)
No
Solution (Elzonris Intravenous)
1000 mcg/mL (per mL): $37,095.22
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Note: Premedicate ~60 minutes prior to each tagraxofusp infusion with an H1-antagonist (eg, diphenhydramine), an H2-antagonist (eg, famotidine), a corticosteroid (eg, methylprednisolone IV), and acetaminophen. Administer cycle 1 in the inpatient setting; observe patients through at least 24 hours after the last infusion. Subsequent cycles may be administered either inpatient or outpatient (if suitable); ensure appropriate monitoring is available and observe patients for a minimum of 4 hours following each infusion.
IV: Administer the tagraxofusp dose and the saline flush via IV infusion syringe pump over a total infusion time of 15 minutes.
Prepare and prime the mini-bifuse Y-connector, infusion set and 0.2-micron polyethersulfone inline filter: Connect the saline flush syringe to one arm of a mini-bifuse Y-connector and ensure the clamp is closed. Connect the tagraxofusp syringe to the other arm of the Y-connector; ensure the clamp is closed. Connect the terminal end of the Y-connector to the microbore tubing. Remove the cap from the supply side of a 0.2-micron polyethersulfone in-line filter and attach it to the terminal end of the microbore tubing. Unclamp the arm of the Y-connector connected to the saline flush syringe; prime the Y-connector up to the intersection (do not prime the full infusion set with NS); re-clamp the Y-connector line on the saline flush arm. Remove the cap on the terminal end of the 0.2-micron filter (save cap); unclamp the arm of the Y-connector connected to the tagraxofusp syringe and prime the entire infusion set, including the filter. Recap the filter, and re-clamp the Y-connector line on the tagraxofusp side; infusion set is now prepared for tagraxofusp infusion.
Infusion: Insert the tagraxofusp syringe into the syringe pump, open the clamp on the tagraxofusp side of the Y-connector, and deliver the dose. Once the tagraxofusp infusion is completed, remove it from the pump and place the saline flush syringe in the pump. Open the clamp on the saline flush side of the Y-connector and resume infusion at the pre-specified flow to push remaining tagraxofusp dose out of the infusion line. Administer within 4 hours of preparation.
IV: Administer the tagraxofusp dose and the saline flush via infusion syringe pump over a total infusion time of 15 minutes. Establish IV access and maintain with NS.
Use the prepared/primed mini-bifuse Y-connector, infusion set and 0.2-micron polyethersulfone inline filter. Insert the tagraxofusp syringe into the syringe pump, open the clamp on the tagraxofusp side of the Y-connector and deliver the dose. Once the tagraxofusp infusion is completed, remove it from the pump and place the saline flush syringe in the pump. Open the clamp on the saline flush side of the Y-connector and resume infusion at the pre-specified flow to push remaining tagraxofusp dose out of the infusion line. Administer within 4 hours of preparation.
Premedicate with an H1-antagonist (eg, diphenhydramine), an H2-antagonist (eg, famotidine), a corticosteroid (eg, methylprednisolone 50 mg IV or equivalent), and acetaminophen ~60 minutes prior to each tagraxofusp infusion. Administer cycle 1 in the inpatient setting; observe patients through at least 24 hours after the last infusion. Subsequent cycles may be administered either inpatient or outpatient (if suitable); ensure appropriate monitoring is available and observe patients for a minimum of 4 hours following each infusion.
Store intact vials in freezer between -25°C and -15°C (-13°F and 5°F). Protect from light (store in the original package until time of use). Thawed vials may be stored at room temperature for approximately 1 hour prior to preparation. Do not refreeze the vial once thawed. Prepared solution for infusion should be administered within 4 hours; keep solution diluted for infusion at room temperature prior to administration. Discard any excess solution.
Treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) (FDA approved in ages ≥2 years and adults).
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Androgens: Hypertension-Associated Agents may enhance the hypertensive effect of Androgens. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Risk C: Monitor therapy
Evaluate pregnancy status within 7 days prior to therapy initiation in patients who could become pregnant. Effective contraception should be used during treatment and for at least 1 week after the last tagraxofusp dose.
Animal reproduction studies have not been conducted. Based on the mechanism of action, adverse effects on fetal development may occur following in utero exposure to tagraxofusp.
Monitor serum albumin, transaminases, and creatinine prior to each dose; evaluate pregnancy status in females of reproductive potential within 7 days prior to initiating tagraxofusp therapy; monitor vital signs (eg, heart rate, blood pressure, weight) prior to each dose; monitor for signs/symptoms of capillary leak syndrome, hepatotoxicity, and hypersensitivity reactions.
Tagraxofusp is a CD123-directed fusion protein which is composed of human interleukin-3 (IL-3) and truncated diphtheria toxin (DT). After binding to CD123, tagraxofusp is internalized, leading to inhibition of protein synthesis and cell death (Sun 2018).
Distribution: 5.1 L; 21.2 L in patients with preexisting anti-drug antibodies
Half-life elimination: 0.7 hours
Excretion: Clearance: 7.1 L/hour; 13.9 L/hour in patients with preexisting anti-drug antibodies
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