RYTELO Solution for injection Ref.[110353] Active ingredients: Imetelstat

2.1. Recommended Dosage

The recommended dosage of RYTELO is 7.1 mg/kg administered as an intravenous infusion over 2 hours every 4 weeks. Discontinue RYTELO if a patient does not experience a decrease in red blood cell (RBC) transfusion burden after 24 weeks of treatment (administration of 6 doses) or if unacceptable toxicity occurs at any time [see Dosage and Administration (2.3)].

2.2. Recommended Premedications

Administer the following pre-treatment medications at least 30 minutes prior to dosing to prevent or reduce potential infusion-related reactions:

• diphenhydramine (or equivalent) 25 mg to 50 mg, intravenously or orally
• hydrocortisone (or equivalent) 100 mg to 200 mg, intravenously or orally

Monitor patients for adverse reactions for at least one hour after the infusion has been completed [see Warnings and Precautions (5.3) and Adverse Reactions (6.1)].

2.3. Dosage Modifications for Adverse Reactions

Recommended dose reductions for Grade 3 and Grade 4 adverse reactions are found in Table 1.

The management of Grade 3 and Grade 4 adverse reactions may require temporary dose delay, dose reduction, or treatment discontinuation and are presented in Table 2 and Table 3. RYTELO treatment should be permanently discontinued if the patient cannot tolerate the lowest dose level of 4.4 mg/kg.

Table 1. Recommended Dose Reduction for RYTELO for Grade 3 and Grade 4 Adverse Reactions:

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.

Table 2. Dosage Modifications for Patients with Hematologic Adverse Reactions (Grade 3 and Grade 4):

Abbreviation: ANC = absolute neutrophil count
^a Severity based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03.

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.

Table 3. Dosage Modifications for Patients with Non-hematologic Adverse Reactions:

Abbreviation: LFT = liver function test
^a Severity based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03.

2.4. Preparation and Administration

RYTELO is provided as a lyophilized powder in a single-dose vial for intravenous infusion only and must be reconstituted and diluted prior to administration.

Use aseptic technique to prepare RYTELO.

RYTELO does not contain a preservative.

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.

Table 4. Reconstitution Volumes:

^a Recommended to use the appropriate combination of vial strengths to most closely match the intended dose based on the patient’s weight.
^b Each vial contains an overfill to account for loss of liquid during preparation and extraction of the reconstituted solution, resulting in the final concentration.

• 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 wellmixed. 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.

Store vials refrigerated at 2°C to 8°C (36°F to 46°F) in original carton.

Do not freeze.