Dosing & Uses
Dosage Forms & Strengths
injection, lyophilized powder for reconstitution
- 5mg/mL( 2-mL, 5.5-mL single-dose vials)
- Includes diluent for reconstitution
Cutaneous T-Cell Lymphoma
Indicated for CTCL in patients who have received at least 1 prior systemic therapy
14 mg/m2 IV on days 1, 8, and 15 of 28-d cycle
Continue until disease progression or intolerable toxicity
Peripheral T-Cell Lymphoma
Indicated for PTCL in patients who have received at least 1 prior systemic therapy
14 mg/m2 IV on days 1, 8, and 15 of 28-d cycle
Continue until disease progression or intolerable toxicity
Dosage Modifications
Nonhematologic toxicities (except alopecia)
- Grade 2 or 3 toxicity: Hold dose until toxicity declines to Grade 1 or baseline, then restart at 14 mg/m2
- If Grade 3 toxicity recurs, hold dose until toxicity returns to Grade 1 or baseline and the dose should be permanently reduced to 10 mg/m2
- Grade 4 toxicity: Hold dose 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 dose until toxicity improves to ANC >1.5×109/L and/or platelet count >75×109/L or baseline, then restart at 14 mg/m2
- Grade 4 febrile (>38.5°C) neutropenia or thrombocytopenia that requires platelet transfusion: Delay dose until the specific cytopenia returns to Grade 1 or baseline, and then permanently reduce dose to 10 mg/m2
Renal impairment
- No dose adjustment required
- Pharmacokinetics of romidepsin not influenced by renal impairment
Hepatic impairment
- Mild: No dose adjustment required
- Moderate (bilirubin levels >1.5x to ≤3x ULN): Reduce starting dose to 7 mg/m2
- Severe (bilirubin levels >3x ULN): Reduce starting dose to 5 mg/m2
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse 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
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, 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
Drug interaction overview
- Coadministration with other drugs that prolong QT interval (eg, sotalol, dofetilide, erythromycin) may increase risk for serious arrhythmias
- 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 & Lactation
Pregnancy
Based on its mechanism of action and findings from animal studies, may cause embryo-fetal harm when administered to a pregnant woman
There are no available data on use in pregnant women to inform a drug associated risk of major birth defects and miscarriage
Advise women of the potential risk to fetus and to avoid becoming pregnant during treatment and for at least 1 month after last dose
Animal data
- In an animal reproductive study, romidepsin was embryocidal and caused adverse developmental outcomes including embryofetal toxicity and malformations at exposures below those in patients at the recommended dose
Pregnancy testing
- Perform pregnancy testing in females of reproductive potential within 7 days before initiating
Contraception
- Females of reproductive potential: Use effective contraception during treatment and for at least 1 month after last dose
- May reduce the effectiveness of estrogen-containing contraceptives; use alternative methods of non-estrogen containing contraception (eg, condoms, intrauterine devices)
- Males with female partners of reproductive potential: Use effective contraception to avoid fathering a child during treatment and for at least 1 month after last dose
Infertility
- Based on findings in animals, romidepsin has the potential to affect male and female fertility
Lactation
- There are no data on presence of drug or its metabolites in human milk, effects on breastfed children, or effects on milk production
- Advise lactating women not to breastfeed during treatment and for at least 1 week after last dose
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
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
Absorption
Peak plasma concentration: 377 ng/mL
AUC: 1549 ng⋅hr/mL
Distribution
Protein bound: 92-94%
Found to be a BSEP and OATP1 inhibitor
Metabolism
Extensive metabolism by CYP3A4 with minor contribution from CYP3A5, CYP1A1, CYP2B6, and CYP2C19
Elimination
Half-life: ~3 hr
No accumulation of plasma concentration of romidepsin was observed after repeated dosing
Administration
IV Compatibility
0.9% NaCl
IV Preparation
Handle according to recommended safe handling procedures for cytotoxic drugs
Reconstitute single-dose vials with supplied diluent (10-mg vial with 2.2 mL ; 27.5-mg vial with 5.5 mL)
Swirl vial contents until there are no visible particles in the resulting solution; reconstituted solution will contain 5 mg/mL
Withdraw and inject desired amount from vials into 500 mL 0.9% NaCl
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
Storage
Store according to recommended safe handling procedures for cytotoxic drugs
Unopened vials: Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF) in the carton; protect from light
Reconstituted vials: Stable for at least 8 hr at room temperature
Diluted solutions: Store at room temperature for up to 24 hr
Images
Patient Handout
Formulary
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