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ISTODAX (romidepsin) for injection
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use ISTODAX safely and effectively. See full prescribing information for ISTODAX.
ISTODAX ® (romidepsin) for injection, for intravenous use
Initial U.S. Approval: 2009
RECENT MAJOR CHANGES
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Dosage and Administration (2.3) 7/2016
INDICATIONS AND USAGE
ISTODAX is a histone deacetylase (HDAC) inhibitor indicated for:
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Treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy (1).
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Treatment of peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior therapy (1).
These indications are based on response rate. Clinical benefit such as improvement in overall survival has not been demonstrated (1).
DOSAGE AND ADMINISTRATION
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14 mg/m2 administered intravenously (IV) over a 4-hour period on days 1, 8, and 15 of a 28-day cycle. Repeat cycles every 28 days provided that the patient continues to benefit from and tolerates the drug (2.1).
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Discontinue or interrupt treatment (with or without dose reduction to 10 mg/m2) to manage drug toxicity (2.2).
DOSAGE FORMS AND STRENGTHS
ISTODAX for injection, 10 mg ( 3).
CONTRAINDICATIONS
None (4).
WARNINGS AND PRECAUTIONS
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Myelosuppression: ISTODAX can cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia; monitor blood counts during treatment with ISTODAX; interrupt and/or modify the dose as necessary (5.1).
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Infections: Fatal and serious infections. Reactivation of DNA viruses (Epstein Barr and hepatitis B). Consider monitoring and prophylaxis in patients with evidence of prior hepatitis B (5.2).
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Electrocardiographic (ECG) changes: Consider cardiovascular monitoring in patients with congenital long QT syndrome, a history of significant cardiovascular disease, and patients taking medicinal products that lead to significant QT prolongation. Ensure that potassium and magnesium are within the normal range before administration of ISTODAX (5.3).
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Tumor lysis syndrome: Patients with advanced stage disease and/or high tumor burden are at greater risk and should be closely monitored and appropriate precautions taken (5.4).
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Embryo-fetal toxicity: ISTODAX may cause fetal harm when administered to a pregnant woman. Advise women of potential hazard to the fetus and to avoid pregnancy while receiving ISTODAX (5.5, 8.1).
ADVERSE REACTIONS
The most common adverse reactions were neutropenia, lymphopenia, thrombocytopenia, infections, nausea, fatigue, vomiting, anorexia, anemia, and ECG T-wave changes (6).
To report SUSPECTED ADVERSE REACTIONS, contact Celgene Corporation at 1-888-423-5436 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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Carefully monitor prothrombin time (PT) and International Normalized Ratio (INR) in patients concurrently administered ISTODAX and warfarin or coumarin derivatives (7.1).
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Monitor for toxicities related to increased romidepsin exposure when co-administering romidepsin with strong CYP3A4 inhibitors (7.2).
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Avoid use with rifampin and strong CYP3A4 inducers (7.3).
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Revised: 7/2016
FULL PRESCRIBING INFORMATION: CONTENTS*
Sections or subsections omitted from the full prescribing information are not listed.
1 INDICATIONS AND USAGE
ISTODAX is indicated for:
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Treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy.
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Treatment of peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior therapy.
These indications are based on response rate. Clinical benefit such as improvement in overall survival has not been demonstrated.
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
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Grade 2 or 3 toxicity: Treatment with romidepsin should be delayed until toxicity returns to ≤ Grade 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 1 or baseline and the dose should be permanently reduced to 10 mg/m2.
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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.
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Romidepsin should be discontinued if Grade 3 or 4 toxicities recur after dose reduction.
Hematologic toxicities
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Grade 3 or 4 neutropenia or thrombocytopenia: Treatment with romidepsin should be delayed until the specific cytopenia returns to ANC ≥1.5×109/L and platelet count ≥75×109/L or baseline, then therapy may be restarted at 14 mg/m2.
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Grade 4 febrile (≥ 38.5ºC) neutropenia or thrombocytopenia that requires platelet transfusion: Treatment with romidepsin should be delayed until the specific cytopenia returns to ≤ Grade 1 or baseline, and then the dose should be permanently reduced to 10 mg/m2.
2.3 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.
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Each 10 mg single-dose vial of ISTODAX must be reconstituted with 2.2 mL of the supplied diluent.
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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.
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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.
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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.
3 DOSAGE FORMS AND STRENGTHS
ISTODAX is supplied as a kit which includes a sterile, lyophilized powder in a 10 mg single-dose vial containing 11 mg of romidepsin and 22 mg of the bulking agent, povidone, USP. In addition, each kit includes a single-dose sterile vial containing 2.4 mL (2.2 mL deliverable volume) of the diluent composed of 80% propylene glycol, USP, and 20% dehydrated alcohol, USP.
4 CONTRAINDICATIONS
5 WARNINGS AND PRECAUTIONS
5.1 Myelosuppression
Treatment with ISTODAX can cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia. Monitor blood counts regularly during treatment with ISTODAX, and modify the dose as necessary [see Dosage and Administration (2.2) and Adverse Reactions (6)].
5.2 Infections
Fatal and serious infections, including pneumonia, sepsis, and viral reactivation, including Epstein Barr and hepatitis B viruses, have been reported in clinical trials with ISTODAX. These can occur during treatment and within 30 days after treatment. The risk of life threatening infections may be greater in patients with a history of prior treatment with monoclonal antibodies directed against lymphocyte antigens and in patients with disease involvement of the bone marrow [see Adverse Reactions (6)].
Reactivation of hepatitis B virus infection has occurred in 1% of PTCL patients in clinical trials in Western populations [see Adverse Reactions (6)]. In patients with evidence of prior hepatitis B infection, consider monitoring for reactivation, and consider antiviral prophylaxis.
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