Rytelo Dosage

Dosage Modifications for Hematologic (Grade 3 and Grade 4) Adverse Reactions

Monitor complete blood cell counts prior to administration of RYTELO, weekly for the first two cycles, prior to each cycle thereafter, and as clinically indicated. Delay the next cycle if absolute neutrophil count is less than 1 × 109/L or platelets are less than 50 × 109/L. Modify dose as described in Table 2.

Dosage Modifications for Non-hematologic Adverse Reactions

Dosage modifications for infusion-related reactions and other adverse drug reactions, including elevated liver function tests (LFTs), are described in Table 3. Monitor liver function tests prior to administration of RYTELO, weekly for the first cycle, prior to each cycle thereafter, and as clinically indicated.

Reconstitution:

• Calculate the dose of RYTELO needed based on the patient's body weight (kg).
• Determine the number of RYTELO vials needed to achieve the required dose (total mg) per Table 4. More than one vial may be needed to achieve a full dose.
• Remove the RYTELO vials from the refrigerator and allow the vials to sit for 10 minutes to 15 minutes (not to exceed 30 minutes) to adjust to room temperature 20°C to 25°C (68°F to 77°F) before use.
• Reconstitute each vial of RYTELO with the volume of 0.9% Sodium Chloride Injection provided in Table 4 directly onto the lyophilized powder to obtain a concentration of 31.4 mg/mL of imetelstat.

• Swirl each vial gently to avoid foaming until the powder is fully reconstituted (not to exceed 15 minutes). Do not shake.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The reconstituted solution in each vial should appear as a clear to slightly hazy solution, essentially free of visible contaminants, particles and/or particulates. Do not use if discoloration or particulate matter is present.
• Use the reconstituted solution immediately to prepare the RYTELO diluted solution in the infusion bag.

Dilution:

• Calculate the required volume of the reconstituted RYTELO solution needed to obtain the appropriate dose according to the patient's body weight.
• Withdraw a volume equal to the required reconstituted RYTELO solution from a 500 mL infusion bag of 0.9% Sodium Chloride Injection and discard it.
• Add the required volume of reconstituted RYTELO solution into the infusion bag so that the total final volume of RYTELO solution in the bag is approximately 500 mL. Discard any unused portion of the reconstituted solution remaining in each vial.
• Gently invert the infusion bag at least 5 times to ensure that the reconstituted RYTELO is well-mixed. Do not shake the infusion bag prior to administration.

Diluted RYTELO Solution Storage:

• If not used immediately, ensure that diluted solution for infusion is used within the total timeframes specified below, according to storage temperature:
  • When stored at room temperature 20°C to 25°C (68°F to 77°F):
    The total time from the reconstitution of RYTELO to completion of the intravenous infusion should not exceed 18 hours from the time of reconstitution.
  • When stored refrigerated 2°C to 8°C (36°F to 46°F):
    The total time from the reconstitution of RYTELO to completion of the intravenous infusion should not exceed 48 hours from the time of reconstitution.

Administration:

• Administer the diluted RYTELO solution by intravenous infusion only over a period of 2 hours.