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Drugs reference index «Romidepsin»

Romidepsin

Pronunciation: ROE-mi-DEP-sinClass: Multikinase inhibitor

Trade Names:Istodax- Injection, lyophilized powder for solution 10 mg

Pharmacology

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.

Pharmacokinetics

Absorption

C max and AUC 0-∞ were 377 ng/mL and 1,549 ng•h/mL, respectively.

Distribution

Highly protein bound in plasma (92% to 94%) with alpha-1-acid glycoprotein being the principal binding protein.

Metabolism

Extensive metabolism primarily by CYP3A4 with minor contribution from CYP3A5, CYP1A1, CYP2B6, and CYP2C19.

Elimination

Terminal half-life is approximately 3 h.

Special Populations

Renal Function Impairment

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.

Indications and Usage

For treatment of cutaneous T-cell lymphoma in patients who have received at least 1 prior systemic therapy.

Contraindications

None well documented.

Dosage and Administration

Cutaneous T-Cell LymphomaAdults

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 .

General Advice

  • Administer by IV infusion only over 4 h.
  • Reconstitute with 2 mL of the supplied diluent and further dilute in 500 mL of sodium chloride 0.9% injection before IV infusion.
  • Diluted solution is compatible with polyvinyl chloride, ethylene vinyl acetate, and polyethylene infusion bags, as well as glass bottles.

Storage/Stability

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.

Drug Interactions

CYP3A4, moderate inhibitors (eg, aprepitant, diltiazem, fluconazole, grapefruit juice)

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.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

ECG changes (63%); hypotension (23%); supraventricular arrhythmia, ventricular arrhythmia (more than 2%).

CNS

Asthenia/fatigue (77%).

Dermatologic

Pruritus (31%); dermatitis/exfoliative dermatitis (27%).

GI

Nausea (86%); anorexia (54%); vomiting (52%); dysgeusia (40%); constipation (39%); diarrhea (20%).

Hematologic

Anemia (72%); thrombocytopenia (65%); lymphopenia, neutropenia (57%); leukopenia (46%).

Hepatic

Increased AST (28%); increased ALT (22%).

Metabolic

Hypocalcemia (52%); hypoalbuminemia (48%); hypomagnesemia (28%); hypermagnesemia, hypophosphatemia (27%); hypokalemia, hyponatremia (20%); edema (more than 2%).

Miscellaneous

Infections (54%); hyperglycemia (51%); hyperuricemia (33%); pyrexia (23%); central line infection, sepsis (more than 2%).

Precautions

Monitor

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.

Pregnancy

Category D .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

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.

Renal Function

Treat patients with ESRD with caution.

Hepatic Function

Treat patients with moderate and severe hepatic impairment with caution.

CV effects

ECG changes, including T-wave and ST-segment changes, have been reported.

Hematologic effects

Treatment has been reported to cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia.

Patient Information

  • Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
  • Advise patient, family, or caregiver to report any of the following to health care provider: abnormal heartbeat, chest pain, nausea, shortness of breath, vomiting, or any unusual bleeding.
  • Advise women of childbearing potential that romidepsin may reduce the effectiveness of estrogen-containing contraceptives.

Copyright © 2009 Wolters Kluwer Health.

  • Romidepsin MedFacts Consumer Leaflet (Wolters Kluwer)
  • romidepsin Intravenous Advanced Consumer (Micromedex) - Includes Dosage Information
  • Istodax Prescribing Information (FDA)
  • Istodax Consumer Overview

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