Posology : מינונים

2    DOSAGE AND ADMINISTRATION
2.1      Dosing Information
The recommended dose of romidepsin is 14 mg/m2 administered intravenously over a 4-hour period on days 1, 8, and 15 of a 28-day cycle. Cycles should be repeated every 28 days provided that the patient continues to benefit from and tolerates the drug.

2.2      Dose Modification
Nonhematologic toxicities except alopecia
•       Grade 2 or 3 toxicity: Treatment with romidepsin should be delayed until toxicity returns to Grade 0-1 or baseline, then therapy may be restarted at 14 mg/m2. If Grade 3 toxicity recurs, treatment with romidepsin should be delayed until toxicity returns to Grade 0-1 or baseline and the dose should be permanently reduced to 10 mg/m2.
•       Grade 4 toxicity: Treatment with romidepsin should be delayed until toxicity returns to ≤ Grade 1 or baseline, then the dose should be permanently reduced to 10 mg/m2.
•       Romidepsin should be discontinued if Grade 3 or 4 toxicities recur after dose reduction.
Hematologic toxicities
•       Grade 3 or 4 neutropenia or thrombocytopenia: Treatment with romidepsin should be delayed until the specific cytopenia returns to ANC greater than or equal to 1.5×109/L and platelet count greater than or equal to 75×109/L or baseline, then therapy may be restarted at 14 mg/m2.
•       Grade 4 febrile (greater than or equal to 38.5ºC) neutropenia or thrombocytopenia that requires platelet transfusion: Treatment with romidepsin should be delayed until the specific cytopenia returns to less than or equal to Grade 1 or baseline, and then the dose should be permanently reduced to 10 mg/m2.

2.3 Dosage in Patients with Hepatic Impairment
• The use of ISTODAX is not recommended in patients with severe hepatic impairment (bilirubin level > 3 x upper limit normal (ULN) and any AST)
• In patients with moderate hepatic impairment (bilirubin level > 1.5 x ULN to ≤ 3 x ULN, and any AST), reduce the starting dose of ISTODAX to 7 mg/m2 (50% reduction)
• Dose adjustment of ISTODAX is not required for patients with mild hepatic impairment (bilirubin ≤ ULN and AST > ULN or bilirubin > ULN but ≤ 1.5 x ULN, and any AST)

2.4      Instructions for Preparation and Intravenous Administration
ISTODAX is a cytotoxic drug. Use appropriate handling procedures.
ISTODAX must be reconstituted with the supplied diluent and further diluted with 0.9% Sodium Chloride Injection, USP, before intravenous infusion.
ISTODAX and diluent vials contain an overfill to ensure the recommended volume can be withdrawn at a concentration of 5 mg/mL.
•       Each 10 mg single-dose vial of ISTODAX must be reconstituted with 2.2 mL of the supplied diluent.
•       With a suitable syringe, aseptically withdraw 2.2 mL from the supplied diluent vial, and slowly inject it into the ISTODAX (romidepsin) for injection vial. Swirl the contents of the vial until there are no visible particles in the resulting solution. The reconstituted solution will contain ISTODAX 5 mg/mL. The reconstituted ISTODAX vial will contain 2 mL of deliverable volume of drug product. The reconstituted ISTODAX solution is chemically stable for up to 8 hours at room temperature.
•       Extract the appropriate amount of ISTODAX from the vials to deliver the desired dose, using proper aseptic technique. Before intravenous infusion, further dilute ISTODAX in 500 mL 0.9% Sodium Chloride Injection, USP.
•       Infuse over 4 hours.
The diluted solution is compatible with polyvinyl chloride (PVC), ethylene vinyl acetate (EVA), polyethylene (PE) infusion bags as well as glass bottles, and is chemically stable for up to 24 hours when stored at room temperature. However, it should be administered as soon after dilution as possible.
Parenteral drug products should be inspected visually for particulate matter and discoloration before administration, whenever solution and container permit.