ISTODAX romidepsin Kit
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Histone Deacetylase Inhibitor class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Romidepsin injection is used to treat cutaneous T-cell lymphoma (CTCL; a group of cancers of the immune system that first appear as skin rashes) in people who have already been treated with at least one other medication. Romidepsin injection is in a class of medications called histone deacetylase (HDAC) inhibitors. It works by slowing the growth of cancer cells.
Read the full MedlinePlus article ↗- Romidepsin is used to treat a type of skin cancer called cutaneous T-cell lymphoma, or CTCL. It's specifically for adults who have already tried at least one other systemic treatme...
- The most common things people notice are nausea, fatigue, loss of appetite, and changes in taste. Low blood counts are also very common — your team will check your blood regularly....
- What side effects should I expect, and which ones should I call my doctor about right away?
- Yes — a few important ones. Rifampin (used for tuberculosis) should be avoided entirely. Certain antifungals and other drugs that affect a liver enzyme called CYP3A4 can increase r...
Patient education
Supplement & herbal interactions
Some supplements/herbs that may interact with Romidepsin — tap one for details:
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $2,577.04 | — |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J9319 | $30.713 / J9319 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Istodaxthis 59572-0984-01 | Celgene | 1 kit | — | AP | FDA listed | — |
| Romidepsin 63323-0926-88 | Fresenius | 1 kit | — | AP | FDA listed | — |
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⏳ Availability & generic status
The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.
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🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2025 (Q1-Q4)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 59572-0984-01 You're viewing this | 1 KIT in 1 CARTON (59572-984-01) * 2.2 mL in 1 VIAL, GLASS (59572-962-10) * 2.4 mL in 1 VIAL, GLASS (59572-973-02) | 2010-01-04 | Active |
🧭 About this NDC listing & data coverage
Kit / multi-component package
This NDC identifies a kit — a package containing more than one component. Structured data (pricing, ingredients, equivalents) is often reported per component rather than for the kit NDC itself, which can make this page look thinner than the components' own pages.
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | — Not published for this NDC No photo available yet for this listing. |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | ✓ Available |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE ISTODAX is indicated for the treatment of cutaneous T-cell lymphoma (CTCL) in adult patients who have received at least one prior systemic therapy. ISTODAX is a histone deacetylase (HDAC) inhibitor indicated for the treatment of cutaneous T-cell lymphoma (CTCL) in adult patients who have received at least one prior systemic therapy ( 1 ).
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • 14 mg/m 2 administered intravenously over a 4-hour 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 drug ( 2.1 ). • Discontinue or interrupt treatment (with or without dose reduction to 10 mg/m 2 ) to manage drug toxicity ( 2.2 ). • Reduce starting dose in patients with moderate and severe hepatic impairment ( 2.3 ).
2.1Dosage Information The recommended dosage of romidepsin is 14 mg/m 2 administered intravenously over a 4-hour period on days 1, 8, and 15 of a 28-day cycle. Cycles should be repeated every 28 days provided that the patient continues to benefit from and tolerates the drug.
2.2Dosage Modification Nonhematologic toxicities except alopecia • Grade 2 or 3 toxicity: Treatment with romidepsin should be delayed until toxicity returns to Grade 0-1 or baseline, then therapy may be restarted at 14 mg/m 2 . If Grade 3 toxicity recurs, treatment with romidepsin should be delayed until toxicity returns to Grade 0-1 or baseline and the dose should be permanently reduced to 10 mg/m 2 . • Grade 4 toxicity: Treatment with romidepsin should be delayed until toxicity returns to Grade 0-1 or baseline, then the dose should be permanently reduced to 10 mg/m 2 . • Romidepsin should be discontinued if Grade 3 or 4 toxicities recur after dose reduction.
Hematologic toxicities • Grade 3 or 4 neutropenia or thrombocytopenia: Treatment with romidepsin should be delayed until the specific cytopenia returns to ANC greater than or equal to 1.5×10 9 /L and platelet count greater than or equal to 75×10 9 /L or baseline, then therapy may be restarted at 14 mg/m 2 . • Grade 4 febrile (greater than or equal to 38.5ºC) neutropenia or thrombocytopenia that requires platelet transfusion: Treatment with romidepsin should be delayed until the specific cytopenia returns to less than or equal to Grade 1 or baseline, and then the dose should be permanently reduced to 10 mg/m 2 .
2.3Dosage in Patients with Hepatic Impairment For patients with moderate or severe hepatic impairment, reduce the starting dose of ISTODAX as shown in Table 1 and monitor for toxicities more frequently. Dosage adjustment is not required for patients with mild hepatic impairment. Table 1: Recommendations for Starting Dose in Patients with Moderate and Severe Hepatic Impairment Hepatic Impairment Bilirubin Levels ISTODAX Dose ULN=Upper limit of normal.
Moderate greater than 1.5 × ULN to less than or equal to 3 × ULN 7 mg/m 2 Severe greater than 3 × ULN 5 mg/m 2
2.4Instructions for Preparation and Intravenous Administration ISTODAX is a hazardous drug. Use appropriate handling procedures. 1 ISTODAX must be reconstituted with the supplied diluent and further diluted with 0.9% Sodium Chloride Injection, USP, before intravenous infusion.
ISTODAX and diluent vials contain an overfill to ensure the recommended volume can be withdrawn at a concentration of 5 mg/mL. • Each 10 mg single-dose vial of ISTODAX must be reconstituted with 2.2 mL of the supplied diluent. • With a suitable syringe, aseptically withdraw 2.2 mL from the supplied diluent vial, and slowly inject it into the ISTODAX (romidepsin) for injection vial. Swirl the contents of the vial until there are no visible particles in the resulting solution. The reconstituted solution will contain ISTODAX 5 mg/mL.
The reconstituted ISTODAX vial will contain 2 mL of deliverable volume of drug product. The reconstituted ISTODAX solution is chemically stable for up to 8 hours at room temperature. • Extract the appropriate amount of ISTODAX from the vials to deliver the desired dose, using proper aseptic technique. Before intravenous infusion, further dilute ISTODAX in 500 mL 0.9% Sodium Chloride Injection, USP. • Infuse over 4 hours.
The diluted solution is compatible with polyvinyl chloride (PVC), ethylene vinyl acetate (EVA), polyethylene (PE) infusion bags as well as glass bottles, and is chemically stable fo…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS For Injection: 10 mg of romidepsin as a lyophilized white powder in a single-dose vial for reconstitution and further dilution. For injection: 10 mg of romidepsin as a lyophilized powder in single-dose vial for reconstitution ( 3 ).
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None ( 4 ).
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Myelosuppression: ISTODAX can cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia; monitor blood counts during treatment with ISTODAX; interrupt and/or modify the dose as necessary ( 5.1 ). • Infections: Fatal and serious infections. Reactivation of DNA viruses (Epstein Barr and hepatitis B). Consider monitoring and prophylaxis in patients with evidence of prior hepatitis B ( 5.2 ). • Electrocardiographic (ECG) changes: Consider cardiovascular monitoring in patients with congenital long QT syndrome, a history of significant cardiovascular disease, and patients taking medicinal products that lead to significant QT prolongation.
Ensure that potassium and magnesium are within the normal range before administration of ISTODAX ( 5.3 ). • Tumor lysis syndrome: Patients with advanced stage disease and/or high tumor burden are at greater risk and should be closely monitored and appropriate precautions taken ( 5.4 ). • Embryo-fetal toxicity: Can cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential of potential risk to a fetus and to use effective contraception ( 5.5 , 8.1 , 8.3 ).
5.1Myelosuppression Treatment with ISTODAX can cause thrombocytopenia, leukopenia (neutropenia and lymphopenia), and anemia. Monitor blood counts regularly during treatment with ISTODAX and modify the dose as necessary [see Dosage and Administration (2.2) and Adverse Reactions (6.1) ].
5.2Infections Fatal and serious infections have been reported in clinical trials of ISTODAX, including pneumonia, sepsis, and viral reactivation, including reactivation of Epstein Barr and hepatitis B viruses. These infections can occur during and following treatment. The risk of life-threatening infections may be greater in patients with a history of prior treatment with monoclonal antibodies directed against lymphocyte antigens and in patients with disease involvement of the bone marrow [see Adverse Reactions (6.1) ] .
Reactivation of hepatitis B virus infection was reported in 1% of patients in clinical trials. In patients with evidence of prior hepatitis B infection, consider monitoring for reactivation, and consider antiviral prophylaxis. Reactivation of Epstein Barr viral infection leading to liver failure has occurred in recipients of ISTODAX including after ganciclovir prophylaxis.
5.3Electrocardiographic Changes Several treatment-emergent morphological changes in ECGs (including T-wave and ST-segment changes) have been reported in clinical studies. The clinical significance of these changes is unknown [see Adverse Reactions (6.1) ]. In patients with congenital long QT syndrome, patients with a history of significant cardiovascular disease, and patients taking anti-arrhythmic medicines or medicinal products that lead to significant QT prolongation, consider cardiovascular monitoring of ECGs at baseline and periodically during treatment.
Confirm that potassium and magnesium levels are within normal range before administration of ISTODAX [see Adverse Reactions (6.1) ] .
5.4Tumor Lysis Syndrome Tumor lysis syndrome (TLS) has been reported to occur in recipients of ISTODAX, including in 1% of patients with tumor stage CTCL. Patients with advanced stage disease and/or high tumor burden are at greater risk, should be closely monitored, and managed as appropriate.
5.5Embryo-Fetal Toxicity Based on its mechanism of action and findings from animal studies, ISTODAX can cause fetal harm when administered to a pregnant woman. In an animal reproductive study, romidepsin was embryocidal and caused adverse developmental outcomes at exposures below those in patients at the recommended dose of 14 mg/m 2 . Advise females of reproductive potential to use effective contraception during treatment and for 1 month after the last dose.
Advise males with female partners of reproductive potential to use effective contraception during treatment and for 1 month after the last d…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are described in more detail in other sections of the prescribing information. • Myelosuppression [see Warnings and Precautions (5.1) ] • Infections [see Warnings and Precautions (5.2) ] • Electrocardiographic Changes [see Warnings and Precautions (5.3) ] • Tumor Lysis Syndrome [see Warnings and Precautions (5.4) ] The most common adverse reactions (≥30%), excluding laboratory abnormalities, are nausea, fatigue, infections, vomiting, anorexia, electrocardiogram ST-T wave changes, dysgeusia, constipation and pruritis.
Grade 3‐4 laboratory abnormalities (≥10%) include lymphopenia, neutropenia, anemia and thrombocytopenia ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Bristol-Myers Squibb at 1-800-721-5072 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data in the WARNINGS AND PRECAUTIONS reflect exposure to ISTODAX in four clinical trials involving 363 patients with T-cell lymphoma, including 185 patients with CTCL. ISTODAX was administered as a single agent at a dosage of 14 mg/m 2 on days 1, 8, and 15 of a 28-day cycle.
Among 363 patients who received ISTODAX, 21% were exposed for 6 months or longer and 13% were exposed for greater than one year. Cutaneous T-Cell Lymphoma The safety of ISTODAX was evaluated in 185 patients with CTCL in 2 single arm clinical studies in which patients received a dosage of 14 mg/m 2 on days 1, 8, and 15 of a 28-day cycle. Treatment continued as long as the patient benefitted from and tolerated the drug.
The mean duration of treatment in these studies was 5.6 months (range: <1 to 83.4 months). Common Adverse Reactions Table 2 summarizes the most frequent adverse reactions (>20%) regardless of causality using the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE, Version 3.0). Due to methodological differences between the studies, the AE data are presented separately for Study 1 and Study 2.
Adverse reactions are ranked by their incidence in Study 1. Laboratory abnormalities commonly reported (>20%) as adverse reactions are included in Table 2. Table 2.
Adverse Reactions Occurring in >20% of Patients in Either CTCL Study (N=185) Adverse Reactions n (%) Study 1 (n=102) Study 2 (n=83) All grades Grade 3 or 4 All grades Grade 3 or 4 Any adverse reactions 99 (97) 36 (35) 83 (100) 68 (82) Nausea 57 (56) 3 (3) 71 (86) 5 (6) Asthenia/Fatigue 54 (53) 8 (8) 64 (77) 12 (14) Infections 47 (46) 11 (11) 45 (54) 27 (33) Vomiting 35 (34) 1 (<1) 43 (52) 8 (10) Anorexia 23 (23) 1 (<1) 45 (54) 3 (4) Hypomagnesemia 22 (22) 1 (<1) 23 (28) 0 Diarrhea 20 (20) 1 (<1) 22 (27) 1 (1) Pyrexia 20 (20) 4 (4) 19 (23) 1 (1) Anemia 19 (19) 3 (3) 60 (72) 13 (16) Thrombocytopenia 17 (17) 0 54 (65) 12 (14) Dysgeusia 15 (15) 0 33 (40) 0 Constipation 12 (12) 2 (2) 32 (39) 1 (1) Neutropenia 11 (11) 4 (4) 47 (57) 22 (27) Hypotension 7 (7) 3 (3) 19 (23) 3 (4) Pruritus 7 (7) 0 26 (31) 5 (6) Hypokalemia 6 (6) 0 17 (20) 2 (2) Dermatitis/Exfoliative dermatitis 4 (4) 1 (<1) 22 (27) 7 (8) Hypocalcemia 4 (4) 0 43 (52) 5 (6) Leukopenia 4 (4) 0 38 (46) 18 (22) Lymphopenia 4 (4) 0 47 (57) 31 (37) Alanine aminotransferase increased 3 (3) 0 18 (22) 2 (2) Aspartate aminotransferase increased 3 (3) 0 23 (28) 3 (4) Hypoalbuminemia 3 (3) 1 (<1) 40 (48) 3 (4) Electrocardiogram ST-T wave changes 2 (2) 0 52 (63) 0 Hyperglycemia 2 (2) 2 (2) 42 (51) 1 (1) Hyponatremia 1 (<1) 1 (<1) 17 (20) 2 (2) Hypermagnesemia 0 0 22 (27) 7 (8) Hypophosphatemia 0 0 22 (27) 8 (10) Hyperuricemia 0 0 27 (33) 7 (8) Serious Adverse Reactions Infections were the most common type of SAE reported in both studies with 8 patients (8%) in Study 1 and 26 patients (31%) in Study 2 experiencing a…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS • Carefully monitor prothrombin time (PT) and International Normalized Ratio (INR) in patients concurrently administered ISTODAX and warfarin or coumarin derivatives ( 7.1 ). • Monitor for toxicities related to increased romidepsin exposure when co-administering romidepsin with strong CYP3A4 inhibitors ( 7.2 ). • Avoid use with rifampin and strong CYP3A4 inducers ( 7.3 ).
7.1Warfarin or Coumarin Derivatives Prolongation of PT and elevation of INR were observed in a patient receiving ISTODAX concomitantly with warfarin. Monitor PT and INR more frequently in patients concurrently receiving ISTODAX and warfarin [see Clinical Pharmacology (12.3) ].
7.2Drugs That Inhibit CYP3A4 Enzymes Strong CYP3A4 inhibitors increase concentrations of romidepsin [see Clinical Pharmacology (12.3) ]. Monitor for toxicity related to increased romidepsin exposure and follow the dose modifications for toxicity [see Dosage and Administration (2.2) ] when ISTODAX is initially co-administered with strong CYP3A4 inhibitors.
7.3Drugs That Induce CYP3A4 Enzymes Rifampin (a potent CYP3A4 inducer) increased the concentrations of romidepsin [see Clinical Pharmacology (12.3) ] . Avoid co-administration of ISTODAX with rifampin. The use of other potent CYP3A4 inducers should be avoided when possible.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary Based on its mechanism of action and findings from animal studies, ISTODAX can cause embryo-fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on ISTODAX use in pregnant women to inform a drug associated risk of major birth defects and miscarriage. In an animal reproductive study, romidepsin was embryocidal and caused adverse developmental outcomes including embryo-fetal toxicity and malformations at exposures below those in patients at the recommended dose (see Data ).
Advise pregnant women of the potential risk to a fetus and to avoid becoming pregnant while receiving ISTODAX and for at least 1 month after the last dose. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Romidepsin was administered intravenously to pregnant rats during the period of organogenesis at doses of 0.1, 0.2, or 0.5 mg/kg/day. Substantial resorption or postimplantation loss was observed at the high dose of 0.5 mg/kg/day, a maternally toxic dose.
Adverse embryo-fetal effects were noted at romidepsin doses of ≥0.1 mg/kg/day, with systemic exposures (AUC) ≥0.2% of the human exposure at the recommended dose of 14 mg/m 2 /week. Drug-related fetal effects consisted of reduced fetal body weights, folded retina, rotated limbs, and incomplete sternal ossification.
8.2Lactation Risk Summary There are no data on the presence of ISTODAX or its metabolites in human milk, the effects on the breastfed child, or the effects on milk production. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in the breastfed child, advise lactating women not to breastfeed during treatment with ISTODAX and for 1 week after the last dose.
8.3Females and Males of Reproductive Potential ISTODAX can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Pregnancy Testing Perform pregnancy testing in females of reproductive potential within 7 days prior to initiating therapy with ISTODAX. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with ISTODAX and for 1 month after the last dose.
ISTODAX may reduce the effectiveness of estrogen-containing contraceptives. Therefore, alternative methods of non-estrogen containing contraception (e.g., condoms, intrauterine devices) should be used in patients receiving ISTODAX. Males Advise males with female partners of reproductive potential to use effective contraception during treatment with ISTODAX and for 1 month after the last dose.
Infertility Based on findings in animals, romidepsin has the potential to affect male and female fertility [see Nonclinical Toxicology (13.1) ].
8.4Pediatric Use The safety and effectiveness of ISTODAX in pediatric patients have not been established.
8.5Geriatric Use Of the 186 patients with CTCL who received ISTODAX in clinical studies, 51 (28%) were 65 years of age and older, while 16 (9%) were 75 years of age. No overall differences in safety or effectiveness were observed between patients 65 years or age and over and younger patients; however, greater sensitivity of some older individuals cannot be ruled out.
8.6Hepatic Impairment In a hepatic impairment study, ISTODAX was evaluated in 19 patients with advanced cancer and mild (8), moderate (5), or severe (6) hepatic impairment. There were 4 deaths during the first cycle of treatment: 1 patient with mild hepatic impairment, 1 patient with moderate hepatic impairment, and 2 patients with severe hepatic impairment. No dose adjustments are recommended for patients…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on its mechanism of action and findings from animal studies, ISTODAX can cause embryo-fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on ISTODAX use in pregnant women to inform a drug associated risk of major birth defects and miscarriage. In an animal reproductive study, romidepsin was embryocidal and caused adverse developmental outcomes including embryo-fetal toxicity and malformations at exposures below those in patients at the recommended dose (see Data ).
Advise pregnant women of the potential risk to a fetus and to avoid becoming pregnant while receiving ISTODAX and for at least 1 month after the last dose. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Romidepsin was administered intravenously to pregnant rats during the period of organogenesis at doses of 0.1, 0.2, or 0.5 mg/kg/day. Substantial resorption or postimplantation loss was observed at the high dose of 0.5 mg/kg/day, a maternally toxic dose.
Adverse embryo-fetal effects were noted at romidepsin doses of ≥0.1 mg/kg/day, with systemic exposures (AUC) ≥0.2% of the human exposure at the recommended dose of 14 mg/m 2 /week. Drug-related fetal effects consisted of reduced fetal body weights, folded retina, rotated limbs, and incomplete sternal ossification.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of ISTODAX in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Of the 186 patients with CTCL who received ISTODAX in clinical studies, 51 (28%) were 65 years of age and older, while 16 (9%) were 75 years of age. No overall differences in safety or effectiveness were observed between patients 65 years or age and over and younger patients; however, greater sensitivity of some older individuals cannot be ruled out.
🆘 Overdosage ▾
10 OVERDOSAGE No specific information is available on the treatment of overdosage of ISTODAX. Toxicities in a single-dose study in rats or dogs, at intravenous romidepsin doses up to 2.2-fold the recommended human dose based on the body surface area, included irregular respiration, irregular heartbeat, staggering gait, tremor, and tonic convulsions. In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., clinical monitoring and supportive therapy, if required.
There is no known antidote for ISTODAX and it is not known if ISTODAX is dialyzable.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Romidepsin is a histone deacetylase (HDAC) inhibitor. HDACs catalyze the removal of acetyl groups from acetylated lysine residues in histones, resulting in the modulation of gene expression. HDACs also deacetylate non-histone proteins, such as transcription factors.
In vitro, romidepsin causes the accumulation of acetylated histones, and induces cell cycle arrest and apoptosis of some cancer cell lines with IC 50 values in the nanomolar range. The mechanism of the antineoplastic effect of romidepsin observed in nonclinical and clinical studies has not been fully characterized.
12.2Pharmacodynamics Cardiac Electrophysiology At doses of 14 mg/m 2 as a 4-hour intravenous infusion, and at doses of 8 (0.57 times the recommended dose), 10 (0.71 times the recommended dose) or 12 (0.86 times the recommended dose) mg/m 2 as a 1-hour infusion, no large changes in the mean QTc interval (>20 milliseconds) from baseline based on Fridericia correction method were detected. Small increase in mean QT interval (< 10 milliseconds) and mean QT interval increase between 10 to 20 milliseconds cannot be excluded.
Romidepsin was associated with a delayed concentration-dependent increase in heart rate in patients with advanced cancer with a maximum mean increase in heart rate of 20 beats per minute occurring at the 6-hour time point after start of romidepsin infusion for patients receiving 14 mg/m 2 as a 4-hour infusion.
12.3Pharmacokinetics In patients with T-cell lymphomas who received 14 mg/m 2 of romidepsin intravenously over a 4-hour period on days 1, 8, and 15 of a 28-day cycle, geometric mean values of the maximum plasma concentration (C max ) and the area under the plasma concentration versus time curve (AUC 0-∞ ) were 377 ng/mL and 1549 ng*hr/mL, respectively. Romidepsin exhibited linear pharmacokinetics across doses ranging from 1.0 (0.07 times the recommended dose) to 24.9 (1.76 times the recommended dose) mg/m 2 when administered intravenously over 4 hours in patients with advanced cancers.
Distribution Romidepsin is highly protein bound in plasma (92% to 94%) over the concentration range of 50 ng/mL to 1000 ng/mL with α1-acid-glycoprotein (AAG) being the principal binding protein. Romidepsin is a substrate of the efflux transporter P-glycoprotein (P-gp, ABCB1). In vitro, romidepsin accumulates into human hepatocytes via an unknown active uptake process.
Romidepsin is not a substrate of the following uptake transporters: BCRP, BSEP, MRP2, OAT1, OAT3, OATP1B1, OATP1B3, or OCT2. In addition, romidepsin is not an inhibitor of BCRP, MRP2, MDR1 or OAT3. Although romidepsin did not inhibit OAT1, OCT2, and OATP1B3 at concentrations seen clinically (1 μmol/L), modest inhibition was observed at 10 µmol/L.
Romidepsin was found to be an inhibitor of BSEP and OATP1B1. Metabolism Romidepsin undergoes extensive metabolism in vitro primarily by CYP3A4 with minor contribution from CYP3A5, CYP1A1, CYP2B6, and CYP2C19. At therapeutic concentrations, romidepsin did not competitively inhibit CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4 in vitro.
At therapeutic concentrations, romidepsin did not cause notable induction of CYP1A2, CYP2B6 and CYP3A4 in vitro. Therefore, pharmacokinetic drug-drug interactions are unlikely to occur due to CYP450 induction or inhibition by romidepsin when co-administered with CYP450 substrates. Excretion Following 4-hour intravenous administration of romidepsin at 14 mg/m 2 on days 1, 8, and 15 of a 28-day cycle in patients with T-cell lymphomas, the terminal half-life (t ½ ) was approximately 3 hours.
No accumulation of plasma concentration of romidepsin was observed after repeated dosing. Drug Interactions Ketoconazole: Following co-administration of 8 mg/m 2 ISTODAX (4-hour infusion) with ketoconazole, the overall romidepsin exposure was increased by approximately 25% and 10% for AUC 0-∞ and C max , respectively, compared to romidepsin alone, and the difference in AUC 0-…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Romidepsin is a histone deacetylase (HDAC) inhibitor. HDACs catalyze the removal of acetyl groups from acetylated lysine residues in histones, resulting in the modulation of gene expression. HDACs also deacetylate non-histone proteins, such as transcription factors.
In vitro, romidepsin causes the accumulation of acetylated histones, and induces cell cycle arrest and apoptosis of some cancer cell lines with IC 50 values in the nanomolar range. The mechanism of the antineoplastic effect of romidepsin observed in nonclinical and clinical studies has not been fully characterized.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied ISTODAX is supplied as a kit including a sterile, lyophilized powder in a 10 mg single-dose vial containing 11 mg of romidepsin, 22 mg of the bulking agent, povidone, USP, and hydrochloric acid, NF, as a pH adjuster. In addition, each kit includes a single-dose sterile diluent vial containing 2.4 mL (2.2 mL deliverable volume) of 80% propylene glycol, USP, and 20% dehydrated alcohol, USP. NDC 59572-984-01: ISTODAX ® KIT containing 1 vial of romidepsin and 1 vial of diluent for romidepsin per carton.
Storage and Handling ISTODAX (romidepsin) for injection is supplied as a kit containing 2 vials in a single carton. The carton must be stored at 20° to 25°C, excursions permitted between 15° to 30°C. (See USP Controlled Room Temperature.) ISTODAX is a hazardous drug.
Follow applicable special handling and disposal procedures. 1
📋 Description ▾
11 DESCRIPTION Romidepsin, a histone deacetylase (HDAC) inhibitor, is a bicyclic depsipeptide. At room temperature, romidepsin is a white powder and is described chemically as (1 S ,4 S ,7 Z ,10 S ,16 E ,21 R )-7-ethylidene-4,21-bis(1-methylethyl)-2-oxa-12,13-dithia-5,8,20,23-tetraazabicyclo[8.7.6]tricos-16-ene-3,6,9,19,22-pentone. The empirical formula is C 24 H 36 N 4 O 6 S 2 .
The molecular weight is 540.71 and the structural formula is: ISTODAX (romidepsin) for injection is intended for intravenous infusion only after reconstitution with the supplied diluent and after further dilution with 0.9% Sodium Chloride, USP. ISTODAX is supplied as a kit containing 2 vials. ISTODAX (romidepsin) for injection is a sterile lyophilized white powder and is supplied in a 10 mg single-dose vial containing 11 mg romidepsin, 22 mg povidone, USP, and hydrochloric acid, NF, as a pH adjuster.
Diluent for ISTODAX is a sterile clear solution and is supplied in a single-dose vial containing 2.4 mL (2.2 mL deliverable volume). Diluent for ISTODAX contains 80% (v/v) propylene glycol, USP and 20% (v/v) dehydrated alcohol, USP. Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling ( Patient Information ). Low Blood Counts Advise patients that treatment with ISTODAX can cause low blood counts and that frequent monitoring of hematologic parameters is required. Patients should be instructed to report fever or other signs of infection, significant fatigue, shortness of breath, or bleeding [see Warnings and Precautions (5.1) ].
Infections Advise patients that infections may occur during treatment with ISTODAX. Advise patients to report fever, cough, shortness of breath with or without chest pain, burning on urination, flu-like symptoms, muscle aches, or worsening skin problems. Advise patients to report any previous history of hepatitis B before starting romidepsin [see Warnings and Precautions (5.2) ].
Tumor Lysis Syndrome Advise patients of the risk of tumor lysis syndrome (especially those with advanced stage disease and/or high tumor burden) to maintain high fluid intake for at least 72 hours after each dose [see Warnings and Precautions (5.4) ]. Nausea and Vomiting Advise patients that nausea and vomiting are common following treatment with ISTODAX. Prophylactic antiemetics are recommended for all patients.
Advise patients to report these symptoms so that appropriate treatment can be instituted [see Adverse Reactions (6.1) ]. Embryo-Fetal Toxicity Advise patients that ISTODAX can cause fetal harm when administered during pregnancy [see Warnings and Precautions (5.5) and Use in Specific Populations (8.1) ]. Contraception Advise females of reproductive potential to use effective contraception during treatment with ISTODAX and for 1 month after the last dose.
Advise males with female partners of reproductive potential to use effective contraception during treatment with ISTODAX and for 1 month after the last dose [ Use in Specific Populations (8.3) ]. Lactation Advise lactating women not to breastfeed during treatment with ISTODAX and for 1 week after the last dose [see Use in Specific Populations (8.2) ]. Infertility Advise females and males of reproductive potential that ISTODAX may cause infertility [see Nonclinical Toxicology (13.1) ].
Marketed by: Bristol-Myers Squibb Company Princeton, NJ 08543 USA ISTODAX ® is a trademark of Celgene Corporation, a Bristol-Myers Squibb company. ISTBAXPI.011/PPI.011