(roe mi DEP sin)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Istodax: 10 mg (1 ea) [contains alcohol, usp, propylene glycol]
Istodax (Overfill): 10 mg (1 ea) [contains alcohol, usp, propylene glycol]
Brand Names: U.S.
- Istodax (Overfill)
- Antineoplastic Agent, Histone Deacetylase (HDAC) Inhibitor
Histone deacetylase inhibitor; catalyzes acetyl group removal from protein lysine residues (including histone and transcription factors). Inhibition of histone deacetylase results in accumulation of acetyl groups, leading to alterations in chromatin structure and transcription factor activation causing termination of cell growth (induces arrest in cell cycle at G1 and G2/M phases) leading to cell death.
Hepatic, primarily via CYP3A4, minor metabolism from CYP3A5, 1A1, 2B6 and 2C19
92% to 94%; primarily to α1-acid glycoprotein
Use: Labeled Indications
Cutaneous T-cell lymphoma: Treatment of cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy
Peripheral T-cell lymphoma: Treatment of peripheral T-cell lymphoma (PTCL) in patients who have received at least one prior therapy
There are no contraindications listed in the manufacturer’s labeling.
Note: Romidepsin is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (MASCC 2016).
Cutaneous T-cell lymphoma: IV: 14 mg/m2 days 1, 8, and 15 of a 28-day treatment cycle; repeat cycle as long as benefit continues and treatment is tolerated.
Peripheral T-cell lymphoma: IV: 14 mg/m2 days 1, 8, and 15 of a 28-day treatment cycle; repeat cycle as long as benefit continues and treatment is tolerated.
Refer to adult dosing.
Dosing: Renal Impairment
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). However, dosage adjustment is not likely necessary since pharmacokinetics are unaffected by renal impairment. Use with caution in patients with end-stage renal disease (has not been studied).
Dosing: Hepatic Impairment
Mild impairment: There are no dosage adjustments provided in the manufacturer’s labeling. However, mild hepatic impairment does not significantly influence the pharmacokinetics of romidepsin.
Moderate or severe impairment: There are no dosage adjustments provided in the manufacturer’s labeling. Use with caution.
Dosing: Adjustment for Toxicity
Nonhematologic toxicity (excluding alopecia):
Grade 2 or 3: Delay treatment until toxicity returns to ≤grade 1 or baseline, may restart at 14 mg/m2
Grade 4 or recurrent grade 3 toxicity: Delay treatment until toxicity returns to ≤grade 1 or baseline, permanently reduce dose to 10 mg/m2
Recurrent grade 3 or 4 toxicity despite dosage reduction: Discontinue treatment
Grade 3 or 4 neutropenia or thrombocytopenia: Delay treatment until ANC ≥1500/mm3 and/or platelets ≥75,000/mm3 or baseline, may restart at 14 mg/m2
Grade 4 febrile neutropenia or thrombocytopenia requiring platelet transfusion: Delay treatment until toxicity returns to ≤grade 1 or baseline, permanently reduce dose to 10 mg/m2
American Society of Clinical Oncology (ASCO) Guidelines for appropriate chemotherapy dosing in obese adults with cancer: Utilize patient’s actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (Griggs, 2012).
Reconstitute each vial of romidepsin with 2.2 mL of supplied diluent to a reconstituted concentration of 5 mg/mL (both the drug and diluent vials contain overfill to ensure the appropriate volume can be withdrawn); swirl until dissolved. The reconstituted vial will contain a deliverable volume of 2 mL of product. Further dilute in 500 mL normal saline; compatible with polyvinyl chloride (PVC), ethylene vinyl acetate (EVA), polyethylene (PE) and glass infusion containers.
Romidepsin is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (MASCC 2016). Antiemetics were used in clinical trials to prevent nausea and vomiting (Piekarz 2009; Piekarz 2011).
Infuse over 4 hours.
Avoid grapefruit juice.
See Trissel’s IV Compatibility Database
Store intact vials at room temperature of 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). The reconstituted solution is stable for 8 hours at room temperature. Solutions diluted for infusion in NS are stable for 24 hours at room temperature; however, the manufacturer recommends use as soon as possible after dilution.
BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Bosentan: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy
Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of RomiDEPsin. Avoid combination
CYP3A4 Inhibitors (Strong): May increase the serum concentration of RomiDEPsin. Monitor therapy
Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates. Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy
Dexamethasone (Systemic): May decrease the serum concentration of RomiDEPsin. Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification
Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification
Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification
MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification
Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination
Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy
Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
RifAMPin: May increase the serum concentration of RomiDEPsin. Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy
St John's Wort: May decrease the serum concentration of RomiDEPsin. Avoid combination
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination
Warfarin: RomiDEPsin may enhance the anticoagulant effect of Warfarin. Monitor therapy
Cardiovascular: ECG changes (ST-T wave changes: 2% to 63%), hypotension (7% to 23%)
Central nervous system: Fatigue (53% to 77%), headache (15% to 34%), chills (11% to 17%)
Dermatologic: Pruritus (7% to 31%), dermatitis (≤27%), exfoliative dermatitis (≤27%)
Endocrine & metabolic: Hypocalcemia (4% to 52%), hyperglycemia (2% to 51%), hypoalbuminemia (3% to 48%), hyperuricemia (≤33%), hypomagnesemia (22% to 28%), hypermagnesemia (≤27%), hypophosphatemia (≤27%), hyponatremia (≤20%), hypokalemia (6% to 20%), weight loss (10% to 15%)
Gastrointestinal: Nausea (56% to 86%), anorexia (23% to 54%), vomiting (34% to 52%), dysgeusia (15% to 40%), constipation (12% to 40%), diarrhea (20% to 36%), abdominal pain (13% to 14%)
Hematologic & oncologic: Anemia (19% to 72%; grades 3/4: 3% to 28%), thrombocytopenia (17% to 72%; grades 3/4: ≤36%), neutropenia (11% to 66%; grades 3/4: 4% to 47%), lymphocytopenia (4% to 57%; grades 3/4: ≤37%), leukopenia (4% to 55%; grades 3/4: ≤45%)
Hepatic: Increased serum AST (3% to 28%), increased serum ALT (3% to 22%)
Infection: Infection (46% to 54%; including infection of central line)
Neuromuscular & skeletal: Weakness (53% to 77%)
Respiratory: Cough (18% to 21%), dyspnea (13% to 21%)
Miscellaneous: Fever (20% to 47%)
1% to 10%:
Cardiovascular: Tachycardia (≤10%), peripheral edema (6% to 10%), chest pain, deep vein thrombosis, edema, prolonged Q-T interval on ECG, pulmonary embolism, supraventricular cardiac arrhythmia, syncope, ventricular arrhythmia
Endocrine & metabolic: Dehydration
Gastrointestinal: Stomatitis (6% to 10%)
Hematologic & oncologic: Tumor lysis syndrome (1% to 2%), febrile neutropenia
Hypersensitivity: Hypersensitivity reaction
Respiratory: Hypoxia, pneumonia, pneumonitis
<1% (Limited to important or life-threatening): Acute renal failure, acute respiratory distress, atrial fibrillation, bacteremia, candidiasis, cardiac failure, cardiogenic shock, ischemic heart disease, multi-organ failure, reactivation of latent Epstein-Barr virus, respiratory failure, septic shock
Concerns related to adverse effects:
• Bone marrow suppression: Anemia, leukopenia, neutropenia, lymphopenia and thrombocytopenia may occur. May require dosage modification. Monitor blood counts during treatment.
• Gastrointestinal toxicity: Romidepsin is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (MASCC 2016).
• Infection: Serious infections (occasionally fatal), including pneumonia, sepsis, and viral reactivation (eg, Epstein Barr and hepatitis B) have occurred during or within 30 days of treatment. Monitor patients with a history of hepatitis B infections closely for viral reactivation; consider antiviral prophylaxis. Epstein Barr reactivation leading to liver failure has also been reported, with ganciclovir antiviral prophylaxis failure in one case. The risk of life-threatening infection may be increased in patients who have received prior treatment with antilymphocytic monoclonal antibodies or who have disease involvement in the bone marrow.
• QTc prolongation/ECG changes: QTc prolongation has been observed; use caution in patients with a history of QTc prolongation, congenital long QT syndrome, with medications known to prolong the QT interval, or with pre-existing cardiac disease. Obtain baseline and periodic ECG (12-lead); monitor and correct electrolyte (potassium, magnesium, and calcium) abnormalities prior to and during treatment. T-wave and ST-segment changes have also been reported.
• Tumor lysis syndrome: Tumor lysis syndrome (TLS) has been observed; closely monitor patients with advanced disease and/or with a high tumor burden (risk of TLS is higher). If TLS occurs, initiate appropriate treatment.
• Hepatic impairment: Mild hepatic impairment does not significantly influence the pharmacokinetics of romidepsin (based on pharmacokinetic analysis). The effect of moderate or severe impairment is unknown; use with caution.
• Renal impairment: The pharmacokinetics of romidepsin are unaffected by mild, moderate or severe renal impairment (based on pharmacokinetic analysis). Use with caution in patients with end-stage renal disease (has not been studied).
Concurrent drug therapy issues:
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Serum electrolytes (baseline and periodic; especially potassium and magnesium); CBC with differential and platelets, ECG (baseline and periodic; in patients with significant cardiovascular disease, congenital long QT syndrome, and in patients taking QT-prolonging medications); signs/symptoms of infection or tumor lysis syndrome
Pregnancy Risk Factor
Adverse events were observed in animal reproduction studies. Based on the mechanism of action, romidepsin may cause fetal harm if administered during pregnancy.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience headache, constipation, diarrhea, lack of appetite, abdominal pain, weight loss, nausea, vomiting, change in taste, or mouth sores. Have patient report immediately to prescriber signs of electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting), signs of infection, signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), swelling of arms or legs, shortness of breath, angina, tachycardia, abnormal heartbeat, dizziness, passing out, severe loss of strength and energy, urinary retention, change in amount of urine passed, or signs of tumor lysis syndrome (tachycardia or abnormal heartbeat; any passing out; urinary retention; muscle weakness or cramps; nausea, vomiting, diarrhea or lack of appetite; or feeling sluggish) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
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Other brands: Istodax