Panobinostat, sold under the brand name Farydak, is a medication used for the treatment of multiple myeloma. It is a hydroxamic acid and acts as a non-selective histone deacetylase inhibitor. Panobinostat was approved for medical use in the United States in 2015 and is administered orally as a systemic oncology agent in combination regimens, most notably with proteasome inhibitors and corticosteroids for relapsed or refractory disease. Mechanistically, the hydroxamic acid moiety chelates the zinc ion in HDAC catalytic sites, producing broad inhibition of class I, II and IV HDAC enzymes, which increases histone acetylation, alters chromatin structure and gene expression, and promotes cell cycle arrest and apoptosis in malignant plasma cells. Pharmacokinetic characteristics include oral absorption with variable bioavailability, extensive plasma protein binding, hepatic metabolism primarily involving CYP isoforms and an elimination half life on the order of hours to a day depending on patient factors. Clinically relevant safety considerations include myelosuppression, gastrointestinal toxicity, fatigue and potential cardiac effects such as QT interval prolongation, and dosing and monitoring recommendations follow the approved label to balance efficacy and tolerability.
Parent: Panobinostat
Parent: Panobinostat
Typical quality and stability control for panobinostat active pharmaceutical ingredient includes assay acceptance criteria and limits for related substances determined by validated high performance liquid chromatography methods; a specification commonly targets assay purity of about 98 percent or greater, individual specified impurities controlled at low levels typically in the range of 0.1 to 0.5 percent depending on the impurity identity, and total related substances generally limited to approximately 1.0 to 1.5 percent. Identified related compounds and degradants that are monitored during manufacture and stability testing include N-oxide and other oxidative derivatives, N- or O-dealkylated species, desmethyl variants, amide or hydroxamate hydrolysis products and positional isomers; potential genotoxic or reactive impurities are assessed and controlled in accordance with ICH M7 guidance and local regulatory requirements, and residual solvents and elemental impurities are controlled per ICH Q3C and Q3D limits.
Panobinostat functions as a histone deacetylase inhibitor that increases acetylation of histones and nonhistone proteins, leading to changes in gene transcription, induction of cell cycle arrest and promotion of apoptosis in malignant cells; it is used clinically as part of combination therapy to treat relapsed or refractory multiple myeloma.
Panobinostat has not been universally withdrawn worldwide, but development or marketing for specific indications or by certain sponsors has been reduced or discontinued in some settings for reasons that include an unfavorable benefit risk profile in particular indications, safety and tolerability concerns, limited commercial uptake, or strategic business decisions; specific discontinuations should be confirmed from regulatory communications or the product marketing authorization holder.
Panobinostat is an anti-cancer drug but not a traditional alkylating or antimetabolite chemotherapy agent; it is an epigenetic targeted therapy classified as a histone deacetylase inhibitor that exerts cytotoxic and cytostatic effects on tumor cells and is used systemically in oncology.
Another name for panobinostat is LBH589, which is its development code, and it is marketed under the brand name Farydak.
