2 DOSAGE AND ADMINISTRATION
2.1 Premedication and Special Considerations
- Premedicate adults with acetaminophen 650 mg orally and diphenhydramine 50 mg orally or intravenously 1 hour prior to MYLOTARG dosing and 1 mg/kg methylprednisolone or an equivalent dose of an alternative corticosteroid within 30 minutes prior to infusion of MYLOTARG.
- Premedicate pediatric patients 1 month and older with acetaminophen 15 mg/kg (maximum of 650 mg) and diphenhydramine 1 mg/kg (maximum of 50 mg) 1 hour prior to MYLOTARG dosing, and 1 mg/kg methylprednisolone orally or intravenously within 30 minutes prior to infusion of MYLOTARG; additional doses of acetaminophen and diphenhydramine may be administered every 4 hours after the initial pretreatment dose. Repeat with the same dose of methylprednisolone or an equivalent corticosteroid for any sign of an infusion reaction, such as fever, chills, hypotension, or dyspnea during the infusion or within 4 hours afterwards [see Warnings and Precautions (5.2)].
- Use appropriate measures to prevent tumor lysis syndrome.
- For patients with hyperleukocytosis (leukocyte count greater than or equal to 30 Gi/L), cytoreduction is recommended prior to administration of MYLOTARG.
2.2 Recommended Dosage
Newly-Diagnosed De Novo CD33-positive AML (Combination Regimen)
The recommended dose of MYLOTARG in adults is 3 mg/m2. A treatment course including MYLOTARG in combination therapy for adults with newly-diagnosed de novo CD33-positive AML consists of 1 induction cycle and 2 consolidation cycles [see Clinical Studies (14.1)].
For the induction cycle, the recommended dose of MYLOTARG is 3 mg/m2 (up to one 4.5 mg vial) on Days 1, 4, and 7 in combination with daunorubicin and cytarabine. For patients requiring a second induction cycle, do NOT administer MYLOTARG during the second induction cycle.
For the consolidation cycles, the recommended dose of MYLOTARG is 3 mg/m2 on Day 1 (up to one 4.5 mg vial) in combination with daunorubicin and cytarabine.
Newly-Diagnosed CD33-positive AML (Single-agent Regimen)
A treatment course of MYLOTARG as a single agent for adults with newly-diagnosed CD33-positive AML consists of 1 cycle of induction and up to 8 cycles of continuation therapy [see Clinical Studies (14.1)].
For the induction cycle, the recommended dose of MYLOTARG is 6 mg/m2 (not limited to one 4.5 mg vial) as a single agent on Day 1, and 3 mg/m2 (not limited to one 4.5 mg vial) on Day 8.
For continuation, the recommended dose of MYLOTARG is 2 mg/m2 (not limited to one 4.5 mg vial) as a single agent on Day 1 every 4 weeks.
2.3 Dosage Modifications for Toxicities
Monitor blood counts frequently through resolution of cytopenias. Monitor blood counts and chemistries at least three times per week through recovery from treatment-related toxicities. Management of some adverse reactions [see Warnings and Precautions (5), Adverse Reactions (6)] may require dose interruptions or permanent discontinuation of MYLOTARG. Table 1 shows the dose modification guidelines for hematologic and nonhematologic toxicities.
|Hematologic and Nonhematologic Toxicities||Recommended Action|
|Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase; VOD=veno-occlusive disease; ULN=upper limit of normal.|
|For patients receiving MYLOTARG in combination therapy|
|For all patients receiving MYLOTARG (Monotherapy or in Combination)|
|Total bilirubin greater than 2 × ULN, or AST and/or ALT greater than 2.5 × ULN||
|Other severe or life-threatening non-hematologic toxicities||
2.4 Instructions for Reconstitution, Dilution, and Administration
Use appropriate aseptic technique for the reconstitution and dilution procedures. Protect the reconstituted and diluted MYLOTARG solution from light.
- MYLOTARG is a cytotoxic drug. Follow applicable special handling and disposal procedures.1
- Calculate the dose (mg) and number of vials of MYLOTARG required.
- Prior to reconstitution, allow drug product vials to reach ambient temperature for approximately 5 minutes.
- Reconstitute each vial with 5 mL of Sterile Water for Injection, USP to obtain a concentration of 1 mg/mL of MYLOTARG that delivers 4.5 mL (4.5 mg).
- Gently swirl the vial to aid dissolution. DO NOT SHAKE.
- Inspect the reconstituted solution for particulates and discoloration. The reconstituted solution may contain small white to off-white, opaque to translucent, and amorphous to fiber-like particles.
- MYLOTARG contains no bacteriostatic preservatives.
- Use reconstituted solution immediately or after being refrigerated at 2–8°C (36–46°F) for up to 1 hour. PROTECT FROM LIGHT. DO NOT FREEZE.
- Calculate the required volume of the reconstituted solution needed to obtain the appropriate dose according to patient body surface area. Withdraw this amount from the vial(s) using a syringe. PROTECT FROM LIGHT. Discard any unused reconstituted solution left in the vial.
Doses must be mixed to a concentration between 0.075 mg/mL to 0.234 mg/mL according to the following instructions:
- Doses less than 3.9 mg must be prepared for administration by syringe. Add the reconstituted MYLOTARG solution to a syringe with 0.9% Sodium Chloride Injection to a final concentration between 0.075 mg/mL to 0.234 mg/mL. PROTECT FROM LIGHT.
- Doses greater than or equal to 3.9 mg are to be diluted in a syringe or an IV bag in an appropriate volume of 0.9% Sodium Chloride Injection to ensure a final concentration between 0.075 mg/mL to 0.234 mg/mL. PROTECT FROM LIGHT.
- Gently invert the infusion container to mix the diluted solution. DO NOT SHAKE.
- Following dilution with 0.9% Sodium Chloride Injection, MYLOTARG solution should be infused immediately. If not used immediately, store at room temperature (15–25°C; 59–77°F) for up to 6 hours, which includes the 2-hour infusion time and 1-hour, if needed, to allow the refrigerated diluted solution to equilibrate to room temperature. The diluted solution can be refrigerated at 2–8°C (36–46°F) for up to 12 hours which includes up to 1-hour in the vial post-reconstitution. PROTECT FROM LIGHT and DO NOT FREEZE.
- Use an in-line 0.2 micron polyethersulfone (PES) filter for infusion of MYLOTARG.
- Protect the intravenous bag from light using a light-blocking cover during infusion. The infusion line does not need to be protected from light.
- Infuse the diluted solution over 2 hours.
- Do not mix MYLOTARG with, or administer as an infusion with, other medicinal products.