Romidepsin

Summary

Romidepsin (Istodax) is a natural product-derived cyclic depsipeptide HDAC inhibitor isolated from Chromobacterium violaceum. It is FDA-approved for the treatment of cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL) in adults who have received at least one prior systemic therapy. It is administered intravenously.

Mechanism of Action

Romidepsin is a bicyclic depsipeptide prodrug that, upon reduction of its disulfide bond intracellularly, releases a free thiol that chelates zinc ions in the active site of class I and class II HDACs, inhibiting their activity. This leads to hyperacetylation of histones and non-histone proteins, resulting in altered gene expression, cell cycle arrest, apoptosis, and differentiation of malignant cells.

Routes of Administration

Goals & Uses

• Treatment of peripheral T-cell lymphoma (PTCL)OncologyHigh
• HIV latency reversalInfectious Disease / ResearchLow
• Treatment of cutaneous T-cell lymphoma (CTCL)OncologyHigh
• Epigenetic modulation in solid tumorsOncology / ResearchLow

Contraindications

• QTc prolongation / pre-existing significant cardiac arrhythmiaCardiovascularHigh
• Severe hepatic impairmentOrganModerateLiver function concerns
• Congenital long QT syndromeCardiovascular / GeneticHigh
• PregnancyPopulationHighPotential fetal risk or insufficient safety data

Adverse Effects

• ThrombocytopeniaHematologicCommonLow platelet count
• Nausea/vomitingGastrointestinalCommon
• QTc prolongation / ECG changesCardiovascularUncommon
• FatigueGeneralCommonLow energy or tiredness
• InfectionsImmunologicUncommon
• Neutropenia/anemiaHematologicCommon

Drug Interactions

• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine)High
• WarfarinModerate
• QT-prolonging agents (e.g., antiarrhythmics, certain antipsychotics)High
• Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin)High

Population Constraints

• Pediatric patientsAgeRelative
• Breastfeeding womenReproductiveAbsolute
• Patients with electrolyte abnormalities (hypokalemia, hypomagnesemia)MetabolicRelative
• Pregnant womenReproductiveAbsolute

Regulatory Status

• European UnionWithdrawnMarketing authorization was granted but subsequently withdrawn at the request of the marketing authorization holder in 2013; not currently available in the EU.
• United StatesApprovedApproved: Cutaneous T-cell lymphoma (CTCL) in adults with at least one prior systemic therapy, Peripheral T-cell lymphoma (PTCL) in adults with at least one prior systemic therapyApproved by FDA in 2009 (CTCL) and 2011 (PTCL). Orphan drug designation for both indications.
• United KingdomUnknownPost-Brexit status unclear; not listed as actively authorized by MHRA as of last available data.

FDA approved for CTCL in 2009 and PTCL in 2011. Designated as an orphan drug for both indications. The EU approval was withdrawn by the marketing authorization holder in 2013.

Evidence & Sources

No sources recorded yet.