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ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS › ANTINEOPLASTIC AGENTS › OTHER ANTINEOPLASTIC AGENTS › Histone deacetylase (HDAC) inhibitors
panobinostat
L01XH03
Forms & Strengths
- Capsules: 10 mg
- Capsules: 15 mg
- Capsules: 20 mg
Adult Dosing
- Multiple myeloma: 20 mg orally once every other day for 3 weeks (Weeks 1, 2, and 3) followed by a 1-week rest period (Week 4) in a 4-week cycle.
- Administered in combination with bortezomib and dexamethasone.
- Maximum treatment duration: 8 cycles (recommended), continue for 2 additional cycles after achieving confirmed complete response, up to a maximum of 16 cycles.
Pediatric Dosing
- Safety and efficacy in pediatric patients have not been established.
Indications
- Treatment of patients with multiple myeloma who have received at least 2 prior regimens, including bortezomib and an immunomodulatory agent.
Mechanism of Action
- Panobinostat is a pan-deacetylase (pan-DAC) inhibitor that inhibits the enzymatic activity of histone deacetylases (HDACs).
- Inhibition of HDACs results in hyperacetylation of histone proteins, leading to chromatin remodeling and altered gene expression.
- Induces cell cycle arrest and apoptosis in cancer cells, with heightened sensitivity in multiple myeloma cells.
Contraindications
- Severe baseline hepatic impairment.
- History of severe hypersensitivity to panobinostat or any of its excipients.
Adverse Reactions
- Severe diarrhea, nausea, vomiting, and abdominal pain.
- Myelosuppression including severe thrombocytopenia, neutropenia, and anemia.
- Severe cardiac toxicities including ECG changes (QTc prolongation) and arrhythmias.
- Infections including pneumonia, sepsis, and opportunistic infections.
- Hemorrhage and electrolyte disturbances including hypokalemia and hypomagnesemia.
Drug Interactions
- Strong CYP3A inhibitors (e.g., ketoconazole): increase panobinostat exposure; reduce panobinostat dose to 10 mg.
- Strong CYP3A inducers (e.g., rifampin): decrease panobinostat exposure; concomitant use should be avoided.
- Drugs known to prolong the QTc interval: increased risk of ventricular arrhythmias; monitor ECG closely.
Curated Content: Needs Vetting Before Put to Clinical Use