Romidepsin (Istodax) is an anticancer drug that induces apoptosis of tumor cells by inactivating the enzyme histone deacetylase. It is used in the treatment of patients with cutaneous and peripheral T-cell lymphomas.

Romidepsin Uses:

• Cutaneous T-cell lymphoma:

  • Used for treating cutaneous T-cell lymphoma (CTCL) in adult patients who have been given at least one prior systemic therapy

• Peripheral T-cell lymphoma:

  • Used for treating peripheral T-cell lymphoma (PTCL) in adult patients who have been given at least one prior therapy

Romidepsin (Istodax) Dose in Adults

Note: Romidepsin is has a moderate emetic potential; antiemetics are recommended for the prevention of nausea and vomiting.

Romidepsin (Istodax) Dose in the treatment of Cutaneous T-cell lymphoma:

• IV: 14 mg/m² days 1, 8, and 15 of a 28-day treatment cycle; cycle should be repeated as long as benefit continues, and the patient tolerates the treatment.

Romidepsin (Istodax) Dose in the treatment of Peripheral T-cell lymphoma:

• IV: 14 mg/m² days 1, 8, and 15 of a 28-day treatment cycle; cycle should be repeated as long as benefit continues, and the patient tolerates the treatment.

Dose in Children:

Not indicated.

Pregnancy Risk Category: D

• Romidepsin can cause fetal harm if it is given to a pregnant woman, according to the mechanism of action as well as animal reproduction studies.
• Before beginning treatment with romidepsin, it is important to evaluate the pregnancy status of females of reproductive potential.
• Females with reproductive potential should use a non-hormonal contraceptive method for their contraception. This is for treatment for up to 30 days and after they have finished receiving romidepsin.
• Also, effective contraception should be used by males who have female partners with reproductive potential during treatment and for at most 30 days after the last dose.

Use while breastfeeding

• It is not known if it is present in breast milk.
• Manufacturers recommend that breastfeeding be stopped during treatment as well as for at least seven days following the last dose of romidepsin. There is the potential for serious adverse reactions.

Dose in Kidney Disease:

• No dosage adjustments have been provided in the manufacturer’s labeling (has not been studied).
• However, dosage adjustment is not likely necessary since renal impairment does not affect the pharmacokinetics. Use cautiously in ESRD (has not been studied).

Dose in Liver disease:

• Mild impairment (bilirubin ≤ ULN and AST > ULN or bilirubin >1 to 1.5 times ULN and any AST):
  • Initial dosage adjustment not necessary.
• Moderate impairment (bilirubin >1.5 to 3 times ULN):
  • The initial dose should be reduced to 7 mg/m² with frequent monitoring for toxicity.
• Severe impairment (bilirubin >3 times ULN):
  • The initial dose should be reduced to 5 mg/m² with frequent monitoring for toxicity.

Common Side Effects of Romidepsin (Istodax):

• Cardiovascular:

  • ECG Changes
  • Hypotension

• Central Nervous System:

  • Fatigue
  • Headache
  • Chills

• Dermatologic:

  • Pruritus
  • Dermatitis
  • Exfoliative Dermatitis

• Endocrine & Metabolic:

  • Hypocalcemia
  • Hyperglycemia
  • Hypoalbuminemia
  • Hyperuricemia
  • Hypomagnesemia
  • Hypermagnesemia
  • Hypophosphatemia
  • Hyponatremia
  • Hypokalemia
  • Weight Loss

• Gastrointestinal:

  • Nausea
  • Anorexia
  • Vomiting
  • Dysgeusia
  • Constipation
  • Diarrhea
  • Abdominal Pain

• Hematologic & Oncologic:

  • Anemia
  • Thrombocytopenia
  • Neutropenia
  • Lymphocytopenia
  • Leukopenia

• Hepatic:

  • Increased Serum AST
  • Increased Serum ALT

• Infection:

  • Infection

• Neuromuscular & Skeletal:

  • Weakness

• Respiratory:

  • Cough
  • Dyspnea

• Miscellaneous:

  • Fever

Less Common Side Effects of Romidepsin (Istodax):

• Cardiovascular:

  • Tachycardia
  • Peripheral Edema
  • Chest Pain
  • Deep Vein Thrombosis
  • Edema
  • Prolonged Q-T Interval On ECG
  • Pulmonary Embolism
  • Supraventricular Cardiac Arrhythmia
  • Syncope
  • Ventricular Arrhythmia

• Dermatologic:

  • Cellulitis

• Endocrine & Metabolic:

  • Dehydration

• Gastrointestinal:

  • Stomatitis

• Hematologic & Oncologic:

  • Tumor Lysis Syndrome
  • Febrile Neutropenia

• Hepatic:

  • Hyperbilirubinemia

• Hypersensitivity:

  • Hypersensitivity Reaction

• Infection:

  • Sepsis

• Respiratory:

  • Hypoxia
  • Pneumonia
  • Pneumonitis

Contraindications to Romidepsin (Istodax):

The US labeling of the manufacturer does not contain any contraindications. Canadian labeling

• Hypersensitivity to romidepsin and any other component of the formulation

Warnings and precautions

• Suppression of bone marrow

  • It may cause anemia, leukopenia and neutropenia.
  • During treatment, blood counts should be closely monitored.

• Gastrointestinal toxicities:

  • Romidepsin is moderately emetic; antiemetics should be used to prevent nausea and vomiting.

• Infection

  • Infections that can be fatal or severe within a month of treatment have been reported. These include pneumonia, sepsis and viral reactivation (eg Epstein Barr and Hepatitis B). Antiviral prophylaxis and surveillance should be done for patients with hepatitis B history. Epstein Barr reactivation leading to liver failure has also been reported. In one instance, ganciclovir failed antiviral prophylaxis. Patients who have had treatment with antilymphocytic monoclonal antibody treatments in the past or have bone marrow disease may be at greater risk for serious infection.

• ECG changes and QTc prolongation:

  • QTc prolongation has been observed. Patients with QTc prolongation history, congenital long QT Syndrome, concurrent use with medications known to prolong QT intervals, and pre-existing heart disease should be cautious. A baseline and periodic ECG (12 lead) should be taken. Electrolyte (potassium and magnesium) abnormalities should also be checked and corrected before and during treatment. Also, T-wave and ST segment changes have been observed.

• Tumor lysis syndrome

  • TLS has been reported in cases. Patients with advanced disease or high tumor burden (higher risk) should be monitored closely. If TLS is suspected, you should initiate the appropriate treatment.

• Hepatic impairment

  • Based on pharmacokinetic analysis, mild hepatic impairment does not affect the pharmacokinetics. Patients with severe or moderate hepatic impairment should reduce the initial dose. Frequent monitoring for toxicities should be performed, especially during the first cycle.

• Renal impairment

  • Based on pharmacokinetic analysis, romidepsin's pharmacokinetics are not affected by mild, medium, or severe renal impairment. Avoid ESRD.

Romidepsin: Drug Interaction

Monitoring parameters:

• Serum electrolytes (baseline, periodic; insbesondere K+ and Mg++).
• Complete blood count including differential and platelets
• Pregnancy test within 7 days of treatment initiation for females with reproductive potential
• ECG (baseline, periodic; patients with serious cardiovascular disease, congenital QT syndrome and patients on QT-prolonging medication)
• Signs and symptoms of tumor lysis syndrome or infection

How to administer Romidepsin (Istodax)?

IV: Romidepsin has a moderate emetic potential; antiemetics are recommended for the prevention of nausea and vomiting. Should be infused over 4 hours.

Mechanism of action of Romidepsin (Istodax):

• Romidepsin inhibits histone deacetylase, HDAC.
• HDACs are enzymes that remove an acetyl from protein lysine (including transcription factors) and other residues. 
• HDAC inhibition causes the accumulation of acetyl group which leads to cell death.

Protein binding: Highly protein-bound(92% to 94%); primarily to α -acid glycoprotein

Metabolism: Metabolised in the liver, primarily via CYP3A4, minor metabolism from CYP3A5, 1A1, 2B6, and 2C19

Half-life elimination: Almost 3 hours

International Brand Names of Romidepsin:

• Istodax (Overfill)
• Istodax

Romidepsin Brand Names in Pakistan:

No Brands Available in Pakistan.