Istodax

What it is

Istodax is romidepsin 10 mg powder for injection. Romidepsin is an anti-neoplastic agent that belongs to the class of drugs known as histone deacetylase (HDAC) inhibitors. Romidepsin has pleiotropic activity including HDAC inhibition, induction or repression of gene expression, cell cycle arrest, cell differentiation, cell growth inhibition, and induction of apoptosis.

Approved indications

— Treatment of peripheral T-cell lymphoma in patients who have received at least one prior systemic therapy.

Dosing overview

The recommended dose 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 therapy. For patients with moderate hepatic impairment, a dose adjustment of 7 mg/m² administered intravenously over a 4-hour period on days 1, 8, and 15 of a 28-day cycle (50% dose reduction) is recommended. For patients with severe hepatic impairment, a dose adjustment of 5 mg/m² administered intravenously over a 4-hour period on days 1, 8, and 15 of a 28-day cycle (64% dose reduction) is recommended.

Key safety warnings

Treatment with Istodax can cause thrombocytopenia, leukopenia (neutropenia and lymphopenia) and anaemia; therefore, these haematological parameters should be monitored during treatment with Istodax, and the dose should be modified as necessary. Serious and sometimes fatal infections, including pneumonia, sepsis, and viral reactivation (including hepatitis B and Epstein Barr viruses) have been reported in clinical trials with Istodax. These can occur during treatment and within 30 days after treatment, and the risk of life-threatening infections may be higher 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. Reactivation of hepatitis B virus infection has occurred in 1% of PTCL patients in clinical trials in Western populations. Consider monitoring or prophylaxis in patients with evidence of a past history of hepatitis B. QTc prolongation as well as several treatment-emergent morphological changes in ECGs (including T wave and ST-segment changes) have been reported in clinical studies. An ECG should be performed at baseline in all patients. Serum potassium and magnesium should be within the normal range before each administration of Istodax. Nausea and vomiting have very commonly been reported with Istodax; therefore, anti-emetic use is recommended. Tumour lysis syndrome (TLS) has been reported to occur in 2% of patients with Stage III/IV PTCL in clinical trials. Patients with advanced stage disease and/or high tumour burden should be closely monitored, appropriate precautions should be taken, and treatment should be instituted as appropriate.

Contraindications

Hypersensitivity to romidepsin or any of the excipients.

Regulatory history

The TGA approved Istodax for registration on 30 July 2013, with initial registration on the ARTG on 7 August 2013. The approval was granted without conditions regarding chemistry and quality control aspects. The TGA found that quality and chemistry aspects were acceptable after the sponsor agreed to tighten limits for an unidentified impurity and residual tert-butyl alcohol.