Romidepsin

What is Romidepsin?

• Romidepsin (Istodax) is a histone deacetylase (HDAC) inhibitor used for the treatment of cutaneous T-cell lymphoma.

Romidepsin

Romidepsin ball and spoke

Romidepsin bioactivation

What are the uses of this medicine?

• Romidepsin (Istodax) is a prescription medicine used to treat people with a type of cancer called cutaneous T-cell lymphoma (CTCL) after at least one other type of medicine by mouth or injection has been tried.

How does this medicine work?

• Romidepsin acts as a prodrug with the disulfide bond undergoing reduction within the cell to release a zinc-binding thiol.
• The thiol reversibly interacts with a zinc atom in the binding pocket of Zn-dependent histone deacetylase to block its activity.
• Thus it is an 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.
• Romidepsin causes the accumulation of acetylated histones, and induces cell cycle arrest and apoptosis of some cancer cell lines with IC50 values in the nanomolar range.
• The mechanism of the antineoplastic effect of romidepsin observed in nonclinical and clinical studies has not been fully characterized.

What drug interactions can this medicine cause?

Some medicines may affect how Istodax works, or Istodax may affect how other medicines work.

Especially tell your healthcare provider if you take or use:

• warfarin sodium (Coumadin, Jantoven) or any other blood thinner medicine. Ask your healthcare provider if you are not sure if you are taking a blood thinner. Your healthcare provider may want to test your blood more often.
• a medicine to treat abnormal heartbeats
• St. John's wort (Hypericum perforatum)
• Dexamethasone (a steroid)

Medicine for:

• tuberculosis (TB)
• seizures (epilepsy)
• bacterial infections (antibiotics)
• fungal infections (antifungals)
• HIV (AIDS)
• depression

Is this medicine FDA approved?

• Romidepsin was first reported in the scientific literature in 1994, by a team of researchers from Fujisawa Pharmaceutical Company (now Astellas Pharma) in Tsukuba, Japan, who isolated it in a culture of Chromobacterium violaceum from a soil sample obtained in Yamagata Prefecture.
• In 2004, romidepsin received Fast Track designation from the FDA for the treatment of cutaneous T-cell lymphoma, and orphan drug status from the FDA and the European Medicines Agency for the same indication;FDA approval for CTCL was obtained on November 5, 2009.

How should this medicine be used?

Recommended dosage:

• The recommended dosage of romidepsin is 14 mg/m2 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.

• Discontinue or interrupt treatment (with or without dose reduction to 10 mg/m2) to manage drug toxicity.

Reduce starting dose in patients with moderate and severe hepatic impairment as below:

• Moderate hepatic impairment:7 mg/m2
• severe hepatic impairment:5 mg/m2

Administration:

• Istodax will be given to you by your healthcare provider or nurse as an intravenous injection into your vein usually over 4 hours.
• Istodax is usually given on Day 1, Day 8, and Day 15 of a 28-day cycle of treatment.
• Your healthcare provider will decide how long you will receive treatment with Istodax.
• Your healthcare provider will check your blood cell counts and other blood tests regularly during your treatment with Istodax to check for side effects of Istodax. Your healthcare provider may decide to do other tests to check your health as needed.
• Your healthcare provider may stop your treatment, change when you get your treatment, or change the dose of your treatment if you have certain side effects while receiving Istodax.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As injection: 10 mg of romidepsin as a lyophilized powder in single-dose vial for reconstitution

This medicine is available in fallowing brand namesː

• Istodax

What side effects can this medication cause?

The most common side effects of this medicine include:

• nausea, tiredness, vomiting, loss of appetite, changes in sense of taste, constipation, and itching.

Istodax may cause serious side effects, including:

• Low blood cell counts
• Serious infections
• Changes in your heartbeat
• Tumor Lysis Syndrome (TLS)

What special precautions should I follow?

• 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.
• 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.
• Several treatment-emergent morphological changes in ECGs (including T-wave and ST-segment changes) have been reported in clinical studies. 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.
• Tumor lysis syndrome (TLS) has been reported to occur in recipients of Istodax. Patients with advanced stage disease and/or high tumor burden are at greater risk and should be closely monitored and appropriate precautions taken.
• Istodax can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential and males with female partners of reproductive potential of potential risk to a fetus and to use effective contraception.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• irregular respiration
• irregular heartbeat
• staggering gait
• tremor
• tonic convulsions

Treatment of overdosage:

• 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.

Can this medicine be used in pregnancy?

• Based on its mechanism of action and findings from animal studies, Istodax can cause embryo-fetal harm when administered to a pregnant woman.
• There are no available data on Istodax use in pregnant women to inform a drug associated risk of major birth defects and miscarriage.

Can this medicine be used in children?

• The safety and effectiveness of Istodax in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

• Active ingredient: romidepsin
• Inactive ingredients: povidone, hydrochloric acid as a pH adjuster. The diluent contains 80% propylene glycol and 20% dehydrated alcohol.

Who manufactures and distributes this medicine?

Manufactured for: Celgene Corporation Summit, NJ

Manufactured by: Baxter Oncology GmbH Halle/Westfalen, Germany Istodax® is a registered trademark of Celgene Corporation

What should I know about storage and disposal of this medication?

• 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.
• Istodax is a hazardous drug.
• Follow applicable special handling and disposal procedures

• Dailymed label info on Romidepsin
• FDA Romidepsin

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