istodax

14 mg/m 2 administered intravenously 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 ). • Discontinue or interrupt treatment (with or without dose reduction to 10 mg/m 2 ) to manage drug toxicity ( 2.2 ). • Reduce starting dose in patients with moderate and severe hepatic impairment ( 2.3 ). 2.1 Dosage Information The recommended dosage of romidepsin is 14 mg/m 2 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 Dosage 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/m 2 . 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/m 2 . • Grade 4 toxicity: Treatment with romidepsin should be delayed until toxicity returns to Grade 0-1 or baseline, then the dose should be permanently reduced to 10 mg/m 2 . • Romidepsin should be discontinued if Grade 3 or 4 toxicities recur after dose reduction. Hematologic toxicities • Grade 3 or 4…

The following adverse reactions are described in more detail in other sections of the prescribing information. • Myelosuppression [see Warnings and Precautions (5.1) ] • Infections [see Warnings and Precautions (5.2) ] • Electrocardiographic Changes [see Warnings and Precautions (5.3) ] • Tumor Lysis Syndrome [see Warnings and Precautions (5.4) ] The most common adverse reactions (≥30%), excluding laboratory abnormalities, are nausea, fatigue, infections, vomiting, anorexia, electrocardiogram ST-T wave changes, dysgeusia, constipation and pruritis. Grade 3‐4 laboratory abnormalities (≥10%) include lymphopenia, neutropenia, anemia and thrombocytopenia ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data in the WARNINGS AND PRECAUTIONS reflect exposure to ISTODAX in four clinical trials involving 363 patients with T-cell lymphoma, including 185 patients with CTCL. ISTODAX was administered as a single agent at a dosage of 14 mg/m 2 on days 1, 8, and 15 of a 28-day cycle. Among 363 patients…

None. None ( 4 ).

No specific information is available on the treatment of overdosage of ISTODAX. Toxicities in a single-dose study in rats or dogs, at intravenous romidepsin doses up to 2.2-fold the recommended human dose based on the body surface area, included irregular respiration, irregular heartbeat, staggering gait, tremor, and tonic convulsions. In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., clinical monitoring and supportive therapy, if required. There is no known antidote for ISTODAX and it is not known if ISTODAX is dialyzable.

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

Carefully monitor prothrombin time (PT) and International Normalized Ratio (INR) in patients concurrently administered ISTODAX and warfarin or coumarin derivatives ( 7.1 ). • Monitor for toxicities related to increased romidepsin exposure when co-administering romidepsin with strong CYP3A4 inhibitors ( 7.2 ). • Avoid use with rifampin and strong CYP3A4 inducers ( 7.3 ). 7.1 Warfarin or Coumarin Derivatives Prolongation of PT and elevation of INR were observed in a patient receiving ISTODAX concomitantly with warfarin. Monitor PT and INR more frequently in patients concurrently receiving ISTODAX and warfarin [see Clinical Pharmacology (12.3) ]. 7.2 Drugs That Inhibit CYP3A4 Enzymes Strong CYP3A4 inhibitors increase concentrations of romidepsin [see Clinical Pharmacology (12.3) ]. Monitor for toxicity related to increased romidepsin exposure and follow the dose modifications for toxicity [see Dosage and Administration (2.2) ] when ISTODAX is initially co-administered with strong CYP3A4 inhibitors. 7.3 Drugs That Induce CYP3A4 Enzymes Rifampin (a potent CYP3A4 inducer) increased the concentrations of romidepsin [see Clinical Pharmacology (12.3) ] . Avoid co-administration of ISTODAX with rifampin. The use of other potent CYP3A4 inducers should be avoided when possible.