Premedication and Special Considerations:
Adults: Premedicate 1 hour prior to infusion with acetaminophen 650 mg orally and diphenhydramine 50 mg orally or IV. Administer methylprednisolone 1 mg/kg (or equivalent corticosteroid) within 30 minutes prior to infusion.
Pediatrics (≥ 1 month): Premedicate 1 hour prior with acetaminophen 15 mg/kg (max 650 mg) and diphenhydramine 1 mg/kg (max 50 mg). Administer methylprednisolone 1 mg/kg within 30 minutes prior. Additional acetaminophen/diphenhydramine doses can be given every 4 hours. Repeat methylprednisolone for infusion reaction signs.
Implement measures to prevent tumor lysis syndrome.
Cytoreduction is recommended for patients with hyperleukocytosis (leukocytes ≥ 30 Gi/L) prior to MYLOTARG administration.
Recommended Dosage:
Dose: 3extmg/m23extmg/m2 (max one 4.5 mg vial per dose) on Days 1, 4, and 7 for a single course.
Induction (1 cycle): 6extmg/m26extmg/m2 on Day 1, and 3extmg/m23extmg/m2 on Day 8 (doses not limited to one 4.5 mg vial).
Continuation (up to 8 cycles): 2extmg/m22extmg/m2 on Day 1 every 4 weeks (dose not limited to one 4.5 mg vial).
Adults:
Pediatrics (≥ 1 month):
Induction (1 cycle): 3extmg/m23extmg/m2 (max one 4.5 mg vial per dose) on Days 1, 4, and 7 with daunorubicin/cytarabine. Do not give MYLOTARG in a second induction cycle.
Consolidation (2 cycles): 3extmg/m23extmg/m2 (max one 4.5 mg vial per dose) on Day 1 with daunorubicin/cytarabine.
Dose: 3extmg/m23extmg/m2 (for BSA ≥0.6extm2≥0.6extm2) or 0.1extmg/kg0.1extmg/kg (for BSA <0.6extm2<0.6extm2).
Schedule: Given once during Induction 1 and once during Intensification 2 with standard chemotherapy. Not given in Induction 2, Intensification 1, or Intensification 3. Consider risk/benefit before Intensification 2 dose.
Newly-Diagnosed De Novo AML (Combination Regimen):
Newly-Diagnosed AML (Single-Agent Regimen - Adults):
Relapsed or Refractory AML (Single-Agent Regimen - Adults and Pediatrics ≥ 2 years):
Dosage Modifications for Toxicities:
Monitor blood counts frequently. Management may require dose interruption or permanent discontinuation.
Persistent Thrombocytopenia/Neutropenia (Combination Therapy): Discontinue MYLOTARG in consolidation (adults) or delay next cycle (pediatrics) if counts do not recover within specified timeframes/levels. (See Table 1 for specific criteria).
VOD: Discontinue MYLOTARG.
Elevated Bilirubin (>2x ULN) or AST/ALT (>2.5x ULN): Delay dose until recovery. Omit dose if delayed >2 days between sequential infusions.
Infusion-Related Reactions: Interrupt infusion, provide medical management (acetaminophen, diphenhydramine, methylprednisolone). Consider resuming at ≤ half the prior rate upon resolution. Permanently discontinue for severe or life-threatening reactions.
Other Severe/Life-Threatening Non-hematologic Toxicities: Delay treatment until ≤ mild severity. Omit dose if delayed >2 days between sequential infusions.
Reconstitution, Dilution, and Administration:
Follow cytotoxic drug handling procedures. Protect from light throughout.
Reconstitute 4.5 mg vial with 5 mL Sterile Water for Injection (yields 1 mg/mL). Gently swirl, do not shake. Inspect for particles. Use immediately or refrigerate (2-8°C) up to 1 hour.
Dilute calculated volume of reconstituted solution in 0.9% Sodium Chloride Injection to a final concentration between 0.075extmg/mL0.075extmg/mL and 0.234extmg/mL0.234extmg/mL. Use syringe for doses < 3.9 mg; syringe or IV bag for doses ≥ 3.9 mg. Gently invert to mix, do not shake.
Administer diluted solution immediately or store at room temp (15-25°C) up to 6 hours (includes infusion time) or refrigerated (2-8°C) up to 12 hours (includes post-reconstitution time).
Infuse over 2 hours through an in-line 0.2 micron polyethersulfone (PES) filter. Protect IV bag from light during infusion. Do not mix with other drugs.
