Plitidepsin

Summary

Plitidepsin (Aplidin) is a cyclic depsipeptide originally derived from the marine tunicate Aplidium albicans. It is approved in Australia for relapsed/refractory multiple myeloma in combination with dexamethasone. It has also been investigated for antiviral activity against SARS-CoV-2. Its primary mechanism involves inhibition of eEF1A2, disrupting protein synthesis in tumor cells.

Mechanism of Action

Inhibits eukaryotic translation elongation factor 1A2 (eEF1A2), leading to inhibition of protein synthesis, cell cycle arrest, and apoptosis in malignant cells; also demonstrated antiviral activity against SARS-CoV-2 by targeting the host eEF1A protein.

Routes of Administration

Goals & Uses

• Antiviral activity against SARS-CoV-2Infectious DiseaseLow
• Solid tumor treatmentOncologyLow
• Treatment of T-cell lymphomasOncologyLow
• Treatment of relapsed/refractory multiple myelomaOncologyModerate

Contraindications

• Severe hepatic impairmentOrganHighLiver function concerns
• Severe renal impairmentOrganModerateKidney function concerns
• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• Active serious infectionInfectionModerate
• Known hypersensitivity to plitidepsin or excipientsAllergyHigh

Adverse Effects

• Peripheral neuropathyNeurologicalUncommon
• HepatotoxicityHepaticUncommonLiver injury or dysfunction
• Hematologic toxicity (neutropenia, thrombocytopenia)HematologicCommon
• Nausea and vomitingGastrointestinalCommon
• Fatigue/astheniaGeneralCommon
• Myopathy/myalgiaMusculoskeletalCommon

Drug Interactions

• DexamethasoneLow
• P-glycoprotein (P-gp) substrates/inhibitorsModerate
• CYP3A4 inducers (e.g., rifampicin, carbamazepine)Moderate
• CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin)High

Population Constraints

• Pediatric patientsAgeRelative
• Patients with hepatic impairmentOrgan FunctionRelative
• Elderly patients (≥75 years)AgeRelative
• Pregnant or breastfeeding womenReproductiveAbsolute

Regulatory Status

• European UnionInvestigationalNot EMA-approved. Orphan designation granted for multiple myeloma. Conditional marketing authorization not obtained.
• United StatesInvestigationalNot FDA-approved. Received orphan drug designation for multiple myeloma. Investigated in clinical trials including for COVID-19.
• United KingdomUnknownNo MHRA approval documented; status follows EU investigational classification post-Brexit.

Approved by the Therapeutic Goods Administration (TGA) in Australia for multiple myeloma (2018). Not approved by the FDA or EMA for any indication; received orphan drug designation in the US and EU for multiple myeloma. Investigated under clinical trials for COVID-19.

Evidence & Sources

No sources recorded yet.