Romidepsin (Istodax) — Clinical FAQs

Question 1

What is Romidepsin FDA-approved to treat?

Accepted Answer

Romidepsin is FDA-approved for the following oncology indications: 1. Cutaneous T-cell lymphoma (CTCL) — patients who have received at least one prior systemic therapy (FDA approved November 5, 2009) 2. Peripheral T-cell lymphoma (PTCL) — patients who have received at least one prior therapy (FDA approved June 5, 2011; accelerated approval based on overall response rate).

Question 2

How does Romidepsin work (mechanism of action)?

Accepted Answer

Romidepsin is a bicyclic depsipeptide (cyclic peptide) natural product derived from Chromobacterium violaceum that functions as a potent, selective inhibitor of class I (HDAC1, HDAC2, HDAC3, HDAC8) and class II histone deacetylases. Administered as a prodrug, the intracellular disulfide bond is reduced to a free thiol that coordinates the catalytic zinc ion in the HDAC active site, blocking deacetylation of histone and non-histone substrates. Histone hyperacetylation causes chromatin relaxation and reactivation of silenced tumor-suppressor genes, while non-histone substrate acetylation drives G1/S and G2/M cell-cycle arrest, apoptosis via the mitochondrial pathway, and differentiation in malignant T-lymphocytes. Romidepsin exhibits sub-nanomolar potency against class I HDACs and preferential antitumor activity in T-cell lymphomas, where RFC-1 and HDAC expression patterns create a favorable therapeutic window relative to normal lymphocytes.

Question 3

How is Romidepsin administered?

Accepted Answer

Romidepsin is administered Intravenous (IV). Administer romidepsin 14 mg/m² as an IV infusion over 4 hours on Days 1, 8, and 15 of a 28-day cycle.

Question 4

What are the most common side effects of Romidepsin?

Accepted Answer

The most commonly reported side effects of Romidepsin (≥10% incidence) include: Nausea (56-86%), Fatigue (53-77%), Thrombocytopenia (17-65%), Anemia (19-72%), Neutropenia (11-57%) and others (14 total). Consult your oncologist for complete prescribing information.

Question 5

Is Romidepsin safe during pregnancy?

Accepted Answer

Romidepsin pregnancy safety: Based on mechanism of action and animal reproductive toxicity data, romidepsin can cause fetal harm. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Males with female partners of reproductive potential should use contraception during treatment. Not recommended during breastfeeding.. Oncologists should review the complete prescribing information and discuss reproductive risks with patients before initiating therapy.

Romidepsin — Drug Monograph

Mechanism of Action

FDA Indications

Common Side Effects

Clinical Pearl

Related Therapies & Mechanisms