Dosing and uses of Istodax (romidepsin)
Adult dosage forms and strengths
injectable lyophilized powder
- 10mg/vial plus diluent vial
Cutaneous T-Cell Lymphoma
Indicated for CTCL in patients who have received at least 1 prior systemic therapy
14 mg/m² IV infused over 4 hr on days 1, 8, and 15 of 28-d cycle
Treatment discontinuation or interruption with or without dose reduction to 10 mg/m² may be required to manage adverse effects
Peripheral T-Cell Lymphoma
Indicated for PTCL in patients who have received at least 1 prior systemic therapy
14 mg/m² IV infused over 4 hr on days 1, 8, and 15 of 28-d cycle
Treatment discontinuation or interruption with or without dose reduction to 10 mg/sq.meter may be required to manage adverse effects
Dosage modifications
Nonhematologic toxicities (except alopecia)
- Grade 2 or 3 toxicity: Hold treatment until toxicity declines to Grade 1 or baseline, then restart at 14 mg/m²
- If Grade 3 toxicity recurs, hold treatment until toxicity returns to Grade 1 or baseline and the dose should be permanently reduced to 10 mg/m²
- Grade 4 toxicity: Hold treatment until toxicity declines to Grade 1 or baseline, then the dose should be permanently reduced to 10 mg/m²
- Discontinued if Grade 3 or 4 toxicities recur after dose reduction
Hematologic toxicities
- Grade 3 or 4 neutropenia or thrombocytopenia: Hold treatment until toxicity improves to ANC >1.5×10^9/L and/or platelet count >75×10^9/L or baseline, then restart at 14 mg/m²
- Grade 4 febrile (>38.5 degrees C) 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
Renal or hepatic impairment
- Use caution with severe hepatic impairment or end-stage renal disease
Administration
Procedures for safe handling of cytotoxic drugs apply
Pediatric dosage forms and strengths
Safety and efficacy not established
Istodax (romidepsin) adverse (side) effects
>10%
Asthenia/fatigue (53-77%)
Anorexia (23-54%)
Constipation (12-40%)
Diarrhea (20-36%)
Nausea (56-86%)
Vomiting (34-52%)
Anemia (19-72%)
Hypomagnesemia (22-28%)
Neutropenia (11-66%)
Thrombocytopenia (17-72%)
Infections (46-54%)
<10%
Hypotension
EKG changes
Exfoliative dermatitis
Pruritus
Hypocalcemia
Hypokalemia
Leukopenia
Lymphopenia
Hypoalbuminemia
Hyperglycemia
Hyponatremia
Increased LFTs
Warnings
Contraindications
Hypersensitivity
Cautions
QT prolongation; potassium and magnesium should be within normal limits before administration
Coadministration with other drugs that prolong QT interval (eg, sotalol, dofetilide, erythromycin) may increase risk for serious arrhythmias
Tumor lysis syndrome has been reported; Patients with advanced stage disease and/or high tumor burden should be closely monitored and appropriate precautions taken
Monitor hematologic parameters; interrupt/discontinue treatment if thrombocytopenia, leukopenia, or anemia becomes severe
Serious and sometimes fatal infections reported with 30 days after treatment including pneumonia, sepsis, and viral reactivation (eg, Epstein Barr and hepatitis B viruses); risk may be greater in patients with a history of monoclonal antibodies treatment directed against lymphocyte antigens and in patients with disease involvement of the bone marrow
Avoid during pregnancy, no adequate trials exist; based on MOA, likely to cause fetal harm
Binds to estrogen and may reduce effectiveness of oral contraceptives
May increase effect of warfarin (prolonged PT, increased INR)
Strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) may increase romidepsin serum levels
Potent CYP3A4 inducers (eg, dexamethasone, carbamazepine, phenytoin, rifampin, rifabutin, rifapentine, phenobarbital, St. John’s Wort) may decrease romidepsin serum levels
Pregnancy and lactation
Pregnancy category: d
Based on its mechanism of action and findings in animals, romidepsin may cause fetal harm when administered to pregnant women
Embryocidal in an animal reproductive study; resulted in adverse effects on the developing fetus at exposures below those in patients at the recommended dose of 14 mg/sq.meter/week
Lactation: Unknown if excreted in breast milk
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Istodax (romidepsin)
Mechanism of action
Histone deacetylase (HDAC) inhibitor; induces arrest in the cell cycle at G1 and G2/M phases, which in turn causes cell death
Pharmacokinetics
Half-life: 3 hr
Cmax: 377 ng/mL
AUC: 1549 ng*hr/mL
Protein Bound: 92-94%
Metabolism: Extensively by CYP3A4
Administration
IV Compatibility
Solution: 0.9% NaCL
IV Preparation
Handle according to recommended safe handling procedures for cytotoxic drugs
Each 10 mg single-dose vial must be reconstituted with 2.2 mL of supplied diluent.
With a suitable syringe, aseptically withdraw 2.2 mL from supplied diluent vial, and slowly inject into vial for injection; swirl the contents of the vial until there are no visible particles in the resulting solution; the reconstituted solution will contain 5 mg/mL; the reconstituted vial will contain 2 mL of deliverable volume of drug product; the reconstituted solution is chemically stable for up to 8 hours at room temperature
Extract the appropriate amount from the vials to deliver desired dose, using proper aseptic technique; before intravenous infusion, further dilute in 500 mL 0.9% Sodium Chloride Injection, USp
IV Administration
Administer & dispose according to recommended safe handling procedures for cytotoxic drugs
Infuse IV over 4 hr
Administer IV infusion via volumetric infusion pump
Diluted solution compatible w/ PVC, EVA, PE infusion bags, or glass bottles
Stability
Store according to recommended safe handling procedures for cytotoxic drugs
Reconstituted solution stable for at least 8 hr at room temp
Diluted solution stable for 24 hr at room temp
Store unreconstituted vials between 20-25% at controlled room temp
