Trade Names:Istodax- Injection, lyophilized powder for solution 10 mg
Inhibits enzymatic activity of histone deacetylases (HDACs). HDACs catalyze the removal of acetyl groups from acetylated lysine residues in histones, resulting in the modulation of gene expression. HDACs also deacetylate nonhistone proteins, such as transcription factors.
C max and AUC 0-∞ were 377 ng/mL and 1,549 ng•h/mL, respectively.
Highly protein bound in plasma (92% to 94%) with alpha-1-acid glycoprotein being the principal binding protein.
Extensive metabolism primarily by CYP3A4 with minor contribution from CYP3A5, CYP1A1, CYP2B6, and CYP2C19.
Terminal half-life is approximately 3 h.
Romidepsin pharmacokinetics were not affected by mild, moderate, or severe renal impairment. The effect of ESRD on romidepsin pharmacokinetics has not been studied.Hepatic Function Impairment
Mild hepatic impairment had no significant influence on romidepsin pharmacokinetics; the effect of moderate and severe hepatic impairment on the pharmacokinetics of romidepsin is unknown.Elderly
Age did not appear to influence the pharmacokinetics of romidepsin.Gender
Gender did not appear to influence the pharmacokinetics of romidepsin.Race
Race (white patients compared with black patients) did not appear to influence the pharmacokinetics of romidepsin.
For treatment of cutaneous T-cell lymphoma in patients who have received at least 1 prior systemic therapy.
None well documented.
IV 14 mg/m 2 IV over a 4-h 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 therapy.Dosage AdjustmentsAdults Nonhematologic toxicities except alopecia Grade 2 or 3 toxicity
Delay treatment until toxicity returns to grade 1 or less or baseline, then therapy may be restarted at 14 mg/m 2 . If grade 3 toxicity recurs, treatment should be delayed until toxicity returns to grade 1 or less or baseline and the dose should be permanently reduced to 10 mg/m 2 .Grade 4 toxicity
Delay treatment until toxicity returns to grade 1 or less or baseline, then the dose should be permanently reduced to 10 mg/m 2 .
Discontinue if grade 3 or 4 toxicities recur after dose reduction.Hematologic toxicities Grade 3 or 4 neutropenia or thrombocytopenia
Delay treatment until the specific cytopenia returns to ANC 1.5 × 10 9 /L or higher and/or platelet count of 75 × 10 9 /L or higher or baseline, then therapy may be restarted at 14 mg/m 2 .Grade 4 febrile (101.3°F or higher) neutropenia or thrombocytopenia that requires platelet transfusion
Delay treatment until the specific cytopenia returns to grade 1 or less or baseline, and then the dose should be permanently reduced to 10 mg/m 2 .
Store at 68° to 77°F; excursions permitted between 59° to 86°F. Reconstituted solution is stable for at least 8 h at room temperature. Diluted reconstituted solution is stable for at least 24 h at room temperature.
Romidepsin plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Coadminister moderate CYP3A4 inhibitors with caution.CYP3A4, strong inducers (eg, carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine)
Romidepsin plasma concentrations may be reduced, decreasing the pharmacologic effects. If possible, avoid coadministration of strong CYP3A4 inducers.CYP3A4, strong inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole)
Romidepsin plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. If possible, avoid coadministration of strong CYP3A4 inhibitors.P-glycoprotein efflux transport inhibitors (eg, cyclosporine, ranolazine)
Romidepsin plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Coadminister with caution.QT interval prolonging drugs (eg, antiarrhythmic agents [eg, amiodarone, propafenone], drugs that lead to important QT prolongation [eg, pimozide, ziprasidone])
Because of the risk of QT prolongation, consider appropriate CV monitoring, such as monitoring electrolytes and ECG at baseline and periodically during treatment.St. John's wort
Romidepsin plasma concentrations may be reduced, decreasing the pharmacologic effects. If possible, avoid coadministration of St. John's wort.Warfarin
Coadministration may result in PT prolongation and elevated INR. Monitor PT and INR in a patient receiving romidepsin and warfarin concurrently. Adjust the warfarin dose as needed.
None well documented.
ECG changes (63%); hypotension (23%); supraventricular arrhythmia, ventricular arrhythmia (more than 2%).
Pruritus (31%); dermatitis/exfoliative dermatitis (27%).
Nausea (86%); anorexia (54%); vomiting (52%); dysgeusia (40%); constipation (39%); diarrhea (20%).
Anemia (72%); thrombocytopenia (65%); lymphopenia, neutropenia (57%); leukopenia (46%).
Increased AST (28%); increased ALT (22%).
Hypocalcemia (52%); hypoalbuminemia (48%); hypomagnesemia (28%); hypermagnesemia, hypophosphatemia (27%); hypokalemia, hyponatremia (20%); edema (more than 2%).
Infections (54%); hyperglycemia (51%); hyperuricemia (33%); pyrexia (23%); central line infection, sepsis (more than 2%).
Potassium and magnesium should be within the normal range before administration. Monitor electrolytes and ECGs at baseline and periodically during treatment in patients with congenital long QT syndrome, history of CV disease, and patients taking antiarrhythmic medications or medications that can lead to QT prolongation. Monitor hematologic parameters during treatment.
Category D .
Safety and efficacy not established.
No overall differences in safety or effectiveness were observed between elderly or younger patients; however, greater sensitivity of some older patients cannot be ruled out.
Treat patients with ESRD with caution.
Treat patients with moderate and severe hepatic impairment with caution.
ECG changes, including T-wave and ST-segment changes, have been reported.
Treatment has been reported to cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia.
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