ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Romidepsin (Canada: Available via Restricted Access Program only): Drug information

Romidepsin (Canada: Available via Restricted Access Program only): Drug information
(For additional information see "Romidepsin (Canada: Available via Restricted Access Program only): Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Special Alerts
Istodax Canadian Market Availability Update March 2023

Istodax (romidepsin) is now available only under a Restricted Access Program in Canada and should not be initiated in new patients. Istodax will be withdrawn from the Canadian market once the last patient completes treatment.

Istodax was originally authorized under a Notice of Compliance with conditions for the treatment of patients with relapsed/refractory peripheral T-cell lymphoma who were not eligible for transplant and had received at least one prior systemic therapy. However, a confirmatory phase 3 study comparing Istodax in combination with chemotherapy versus chemotherapy alone did not meet the primary efficacy endpoint of progression-free survival.

Further information may be found at https://recalls-rappels.canada.ca/en/alert-recall/istodax-romidepsin-restricted-access-program.

Brand Names: US
  • Istodax
Brand Names: Canada
  • Istodax
Pharmacologic Category
  • Antineoplastic Agent, Histone Deacetylase (HDAC) Inhibitor
Dosing: Adult

Note: Romidepsin is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]). Correct electrolyte (potassium, magnesium) abnormalities prior to and during treatment. Consider antiviral prophylaxis in patients with a history of hepatitis B infection.

Cutaneous T-cell lymphoma

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, relapsed/refractory

Peripheral T-cell lymphoma, relapsed/refractory (off-label use): IV: 14 mg/m2 days 1, 8, and 15 of a 28-day treatment cycle for up to 6 cycles or until disease progression in patients with stable disease, partial response, or complete response (Coiffier 2012) or until disease progression or unacceptable toxicity (Piekarz 2011).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

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: Adult

Mild impairment (bilirubin ≤ ULN and AST > ULN or bilirubin >1 to 1.5 times ULN and any AST): No initial dosage adjustment necessary.

Moderate impairment (bilirubin >1.5 to 3 times ULN): Reduce initial dose to 7 mg/m2; monitor frequently for toxicity.

Severe impairment (bilirubin >3 times ULN): Reduce initial dose to 5 mg/m2; monitor frequently for toxicity.

Dosing: Obesity: Adult

American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (ASCO [Griggs 2021]).

Dosing: Adjustment for Toxicity: Adult

Hematologic toxicity:

Grade 3 or 4 neutropenia or thrombocytopenia: Delay treatment until ANC ≥1,500/mm3 and/or platelets ≥75,000/mm3 or baseline, then may restart at 14 mg/m2.

Grade 4 febrile neutropenia (≥38.5°C [≥101°F]) or thrombocytopenia requiring platelet transfusion: Delay treatment until toxicity returns to ≤ grade 1 or baseline, permanently reduce dose to 10 mg/m2.

Nonhematologic toxicity (excluding alopecia):

Grade 2 or 3: Delay treatment until toxicity returns to ≤ grade 1 or baseline, then 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 romidepsin.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Abnormal T waves on ECG (ST-T wave changes: 2% to 63%), hypotension (7% to 23%)

Dermatologic: Dermatitis (≤27%), exfoliative dermatitis (≤27%), pruritus (7% to 31%)

Endocrine & metabolic: Hyperglycemia (2% to 51%), hypermagnesemia (27%), hyperuricemia (33%), hypoalbuminemia (3% to 48%), hypocalcemia (4% to 52%), hypokalemia (6% to 20%), hypomagnesemia (22% to 28%), hyponatremia (≤20%), hypophosphatemia (27%)

Gastrointestinal: Anorexia (23% to 54%), constipation (12% to 39%), diarrhea (20% to 27%), dysgeusia (15% to 40%), nausea (56% to 86%), vomiting (34% to 52%)

Hematologic & oncologic: Anemia (19% to 72%; grades 3/4: 3% to 16%), leukopenia (4% to 46%; grades 3/4: 22%), lymphocytopenia (4% to 57%; grades 3/4: 37%), neutropenia (11% to 57%; grades 3/4: 4% to 27%), thrombocytopenia (17% to 65%; grades 3/4: 14%)

Hepatic: Increased serum alanine aminotransferase (3% to 22%), increased serum aspartate aminotransferase (3% to 28%)

Infection: Infection (46% to 54%; serious infection: 8% to 31%, including infection of central line, pneumonia, reactivation of latent Epstein-Barr virus, sepsis, viral infection [reactivation])

Nervous system: Fatigue (≤77%)

Neuromuscular & skeletal: Asthenia (≤77%)

Miscellaneous: Fever (20% to 23%)

1% to 10%:

Cardiovascular: Edema (5%)

Hematologic & oncologic: Tumor lysis syndrome (1%)

Infection: Reactivation of HBV (1%)

Respiratory: Dyspnea (4%)

Frequency not defined:

Cardiovascular: Prolonged QT interval on ECG, supraventricular cardiac arrhythmia, ventricular arrhythmia

Endocrine & metabolic: Dehydration

Contraindications

There are no contraindications listed in the manufacturer’s US labeling.

Canadian labeling: Hypersensitivity to romidepsin or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Anemia, leukopenia, neutropenia, lymphopenia and thrombocytopenia may occur.

• Infection: Serious infections (occasionally fatal), including pneumonia, sepsis, and viral reactivation (eg, Epstein Barr and hepatitis B) have occurred during or following romidepsin treatment. 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 preexisting cardiac disease. 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).

Disease-related concerns:

• Hepatic impairment: Mild hepatic impairment does not significantly influence the pharmacokinetics of romidepsin (based on pharmacokinetic analysis).

Dosage form specific issues:

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer's labeling.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Generic: 27.5 mg/5.5 mL (5.5 mL)

Solution Reconstituted, Intravenous:

Istodax: 10 mg (1 ea) [contains alcohol, usp, propylene glycol]

Generic: 10 mg (1 ea)

Generic Equivalent Available: US

Yes

Pricing: US

Solution (romiDEPsin Intravenous)

27.5MG/5.5ML (per mL): $1,919.16

Solution (reconstituted) (Istodax Intravenous)

10 mg (per each): $3,838.38

Solution (reconstituted) (romiDEPsin Intravenous)

10 mg (per each): $3,802.38

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

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]

Administration: Adult

IV: Romidepsin is associated with a moderate emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]).

Must be diluted prior to administration. Infuse over 4 hours.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Use: Labeled Indications

Cutaneous T-cell lymphoma: Treatment of cutaneous T-cell lymphoma in adult patients who have received at least 1 prior systemic therapy.

Use: Off-Label: Adult

Peripheral T-cell lymphoma, relapsed/refractory

Medication Safety Issues
Sound-alike/look-alike issues:

RomiDEPsin may be confused with romiPLOStim

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

Substrate of CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BSEP/ABCB11

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of RomiDEPsin. Risk X: Avoid combination

CYP3A4 Inhibitors (Strong): May increase the serum concentration of RomiDEPsin. Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy

Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification

Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination

Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of RomiDEPsin. Risk C: Monitor therapy

Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification

RifAMPin: May increase the serum concentration of RomiDEPsin. Risk X: Avoid combination

Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Taurursodiol: Histone Deacetylase Inhibitors may enhance the adverse/toxic effect of Taurursodiol. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy

Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Warfarin: RomiDEPsin may enhance the anticoagulant effect of Warfarin. Risk C: Monitor therapy

Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Reproductive Considerations

Evaluate pregnancy status in patients who may become pregnant, within 7 days prior to initiating treatment with romidepsin. Patients who may become pregnant should use an effective nonhormonal method of contraception during treatment and for 1 month after the final romidepsin dose. Patients with partners who may become pregnant should use effective contraception during treatment and for 1 month after the last romidepsin dose.

Pregnancy Considerations

Based on the mechanism of action and findings from animal reproduction studies, romidepsin may cause fetal harm if administered to a pregnant patient.

Breastfeeding Considerations

It is not known if romidepsin is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends to discontinue breastfeeding during treatment and for 1 week after the last romidepsin dose.

Monitoring Parameters

Serum electrolytes (baseline and periodic; especially potassium and magnesium); CBC with differential and platelets (regularly during treatment). Evaluate pregnancy status (within 7 days prior to treatment initiation in patients who may become pregnant). ECG (baseline and periodic; in patients with significant cardiovascular disease, congenital long QT syndrome, and in patients taking QT-prolonging medications). Monitor for signs/symptoms of infection or tumor lysis syndrome.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

Romidepsin is a histone deacetylase (HDAC) inhibitor; HDACs catalyze acetyl group removal from protein lysine residues (including histone and transcription factors). Inhibition of HDAC 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.

Pharmacokinetics (Adult Data Unless Noted)

Protein binding: 92% to 94%; primarily to α1-acid glycoprotein

Metabolism: Hepatic, primarily via CYP3A4, minor metabolism from CYP3A5, 1A1, 2B6, and 2C19

Half-life elimination: ~3 hours

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Hepatic function impairment: Romidepsin clearance decreased with increased severity of hepatic impairment. In patients with cancer, the geometric mean Cmax values after administration of 14, 7, and 5 mg/m2 romidepsin in patients with mild (bilirubin ≤ULN and AST >ULN or bilirubin 1 to 1.5 times ULN and any AST), moderate (bilirubin >1.5 to 3 times ULN and any AST), and severe (bilirubin >3 times ULN and any AST) impairment were approximately 111%, 96%, and 86%, respectively, compared to a 14 mg/m2 dose in patients with normal hepatic function. The geometric mean AUCinf values in patients with mild, moderate, and severe impairment were approximately 144%, 114%, and 116%, respectively, compared to patients with normal hepatic function.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AU) Australia: Istodax;
  • (HK) Hong Kong: Istodax;
  • (JP) Japan: Istodax;
  • (NZ) New Zealand: Istodax;
  • (PR) Puerto Rico: Istodax
  1. <800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
  2. Coiffier B, Pro B, Prince HM, et al. Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J Clin Oncol. 2012;30(6):63163-6. doi:10.1200/JCO.2011.37.4223 [PubMed 22271479]
  3. Griggs JJ, Bohlke K, Balaban EP, et al. Appropriate systemic therapy dosing for obese adult patients with cancer: ASCO guideline update. J Clin Oncol. 2021;39(18):2037-2048. doi:10.1200/JCO.21.00471 [PubMed 33939491]
  4. Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: ASCO guideline update. J Clin Oncol. 2020;38(24):2782-2797. doi:10.1200/JCO.20.01296 [PubMed 32658626]
  5. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
  6. "Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics Committee on Drugs. Pediatrics. 1997;99(2):268‐278. doi:10.1542/peds.99.2.268 [PubMed 9024461]
  7. Istodax (romidepsin) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Co; January 2023.
  8. Istodax (romidepsin) [product monograph]. Saint-Laurent, Quebec, Canada: Celgene Inc; March 2023.
  9. Piekarz RL, Frye AR, Wright JJ, et al, “Cardiac Studies in Patients Treated With Depsipeptide, FK228, in a Phase II Trial for T-Cell Lymphoma,” Clin Cancer Res, 2006, 12(12):3762-73. [PubMed 16778104]
  10. Piekarz RL, Frye R, Prince HM, et al, “Phase 2 Trial of Romidepsin in Patients With Peripheral T-Cell Lymphoma,” Blood, 2011, 117(22):5827-34. [PubMed 21355097]
  11. Piekarz RL, Frye R, Turner M, et al, “Phase II Multi-Institutional Trial of the Histone Deacetylase Inhibitor Romidepsin as Monotherapy for Patients With Cutaneous T-Cell Lymphoma,” J Clin Oncol, 2009, 27(32):5410-7. [PubMed 19826128]
  12. Roila F, Molassiotis A, Herrstedt J, et al; participants of the MASCC/ESMO Consensus Conference Copenhagen 2015. 2016 MASCC and ESMO guideline update for the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting and of nausea and vomiting in advanced cancer patients. Ann Oncol. 2016;27(suppl 5):v119-v133. doi:10.1093/annonc/mdw270 [PubMed 27664248]
  13. Romidepsin injection solution [prescribing information]. North Wales, PA: Teva Pharmaceuticals USA Inc; December 2021.
  14. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/default.html. Updated September 2016. Accessed May 14, 2021.
  15. Zar T, Graeber C, Perazella MA. Recognition, treatment, and prevention of propylene glycol toxicity. Semin Dial. 2007;20(3):217‐219. doi:10.1111/j.1525-139X.2007.00280.x [PubMed 17555487]
Topic 9536 Version 305.0

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟