Usual Adult Dose for Malignant Disease

12 mcg/kg IV over 15 minutes once daily on Days 1 to 5 of a 21-day cycle until disease progression or unacceptable toxicity

Comments:

• Premedicate patients with an H1-histamine antagonist (e.g., diphenhydramine), H2-histamine antagonist (e.g., ranitidine), corticosteroid (e.g., 50 mg IV methylprednisolone or equivalent) and acetaminophen approximately 60 minutes prior to each infusion.
• The dosing period may be extended for dose delays up to Day 10 of the cycle.

Use: For the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN)

Usual Pediatric Dose for Malignant Disease

2 years and older:
12 mcg/kg IV over 15 minutes once daily on Days 1 to 5 of a 21-day cycle until disease progression or unacceptable toxicity

Comments:

• Premedicate patients with an H1-histamine antagonist (e.g., diphenhydramine), H2-histamine antagonist (e.g., ranitidine), corticosteroid (e.g., 50 mg IV methylprednisolone or equivalent) and acetaminophen approximately 60 minutes prior to each infusion.
• The dosing period may be extended for dose delays up to Day 10 of the cycle.

Use: For the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in pediatric patients 2 years and older

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

RECOMMENDED DOSE MODIFICATIONS:

• SERUM ALBUMIN 3.5 g/dL or less or reduced 0.5 g/dL or greater from value measured prior to initiation of the current cycle: See CLS Management Guidelines.
• BODY WEIGHT increase 1.5 kg or greater over pretreatment weight on prior treatment day: See CLS Management Guidelines.
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) increase to 5 times the upper limit of normal (ULN): Withhold therapy until transaminase elevations are 2.5 x ULN or less.
• SERUM CREATININE greater than 1.8 mg/dL or CrCl 60 mL/minute or less: Withhold therapy until serum creatinine resolves to 1.8 mg/dL or less or CrCl is 60 mL/min or greater.
• SYSTOLIC BLOOD PRESSURE greater than or equal to 160 mmHg OR less than or equal to 80 mmHg: Withhold therapy until systolic blood pressure is less than 160 mmHg or greater than 80 mmHg.
• HEART RATE greater than or equal to 130 bpm OR less than or equal to 40 bpm: Withhold therapy until heart rate is less than 130 bpm or greater than 40 bpm.
• BODY TEMPERATURE 38C or greater: Withhold therapy until body temperature is less than 38C.
• MILD OR MODERATE HYPERSENSITIVITY REACTIONS: Withhold therapy until resolution of any mild or moderate hypersensitivity reaction; resume therapy at the same infusion rate.
• SEVERE OR LIFE-THREATENING HYPERSENSITIVITY REACTIONS: Permanently discontinue therapy.

CLS MANAGEMENT GUIDELINES:
PRIOR TO FIRST DOSE IN CYCLE 1:

• Serum albumin less than 3.2 g/dL: Administer this drug when serum albumin is 3.2 g/dL or greater.
• Serum albumin less than 3.5 g/dL: Interrupt dosing until resolved; administer albumin at 25 g IV every 12h or more frequently as practical until serum albumin is greater than or equal to 3.5 g/dL AND not more than 0.5 g/dL lower than the value measured prior to dosing initiation of the current cycle.
• Serum albumin reduced by greater than or equal to 0.5 g/dL from the albumin value measured prior to initiation of the current cycle: Interrupt dosing until resolved; administer albumin at 25 g IV every 12h or more frequently as practical until serum albumin is greater than or equal to 3.5 g/dL AND not more than 0.5 g/dL lower than the value measured prior to dosing initiation of the current cycle.

DURING DOSING:

• A predose body weight that is increased by greater than or equal to 1.5 kg over the previous day's predose weight: Interrupt dosing until resolved; administer albumin at 25 g IV every 12 hours or more frequently as practical and manage fluid status as indicated clinically (e.g., generally with IV fluids and vasopressors if hypotensive and with diuretics if normotensive or hypertensive), until body weight increase has resolved (i.e., the increase is no longer greater than or equal to 1.5 kg greater than the previous day's predose weight).
• Edema, fluid overload and/or hypotension: Interrupt dosing until resolved; administer albumin at 25 g IV every 12 hours or more frequently as practical and manage fluid status as indicated clinically serum albumin is greater than or equal to 3.5 g/dL. Administer 1 mg/kg of methylprednisolone (or an equivalent) per day, until resolution of CLS sign/symptom or as indicated clinically. Aggressive management of fluid status and hypotension if present, which could include IV fluids and/or diuretics or other blood pressure management, until resolution of CLS sign/symptom or as clinically indicated.

NOTE: Administration may resume in the same cycle if all CLS signs/symptoms have resolved and the patient did not require treatment of hemodynamic instability. Administration should be held for the remainder of the cycle if CLS symptoms have not resolved or the patient required treatment for hemodynamic instability (e.g., required administration of IV fluids and/or vasopressors to treat hypotension) (even if resolved), and therapy may only resume in the next cycle if all CLS signs/symptoms have resolved, and the patient is hemodynamically stable.

Precautions

CONTRAINDICATIONS:

• None

Safety and efficacy have not been established in patients younger than 2 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Administer the first cycle of this drug in an inpatient setting. Subsequent cycles may be administered in the inpatient or outpatient setting.

Storage requirements:

• Store in freezer between -25C and -15C (-13F and 5F).
• Protect from light by storing in the original package. Thaw vials at room temperature between 15C and 25C (59F and 77F) prior to preparation.
• Do not refreeze the vial once thawed.
• Do not use beyond expiration date on container.

Reconstitution/preparation techniques:

• The manufacturer product information should be consulted.

IV compatibility:

• Compatible with 0.9% sodium chloride injection.

Monitoring:

• Albumin
• Transaminases
• Creatinine clearance

Frequently asked questions

• What disease is Elzonris (tagraxofusp-erzs) used to treat?