Product Information
Registration Status: ActiveFARYDAK HARD GELATIN CAPSULE 20mg is approved to be sold in Singapore with effective from 2016-08-24. It is marketed by NOVARTIS (SINGAPORE) PTE LTD, with the registration number of SIN15073P.
This product contains Panobinostat 20mg in the form of ORAL CAPSULE. It is approved for ORAL use.
This product is manufactured by Novartis Farmaceutica in SPAIN.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Description
Panobinostat is an oral deacetylace (DAC) inhibitor approved on February 23, 2015 by the FDA for the treatment of multiple myeloma. The approval was accelerated based on progression-free survival, therefore confirmatory trials by the sponsor to demonstrate clinical efficacy in multiple myeloma treatment are in progress of being conducted. Panobinostat is marketed by Novartis under the brand name Farydak. Panobinostat acts as a non-selective histone deacetylase inhibitor (pan-HDAC inhibitor) and it is the most potent DAC inhibiting agent available on the market.
Indication
Panobinostat is indicated in the treatment of multiple myeloma in combination with dexamethasone and bortezomib in patients who have received 2 previous treatment regimens including bortezomib and an immunomodulatory agent. This indication is approved by accelerated approval based on progression free survival as of February 23, 2015.
Mechanism of Action
Panobinostat is a deacetylase (DAC) inhibitor. DACs, also known as histone DACs (HDAC), are responsible for regulating the acetylation of about 1750 proteins in the body; their functions are involved in many biological processes including DNA replication and repair, chromatin remodelling, transcription of genes, progression of the cell-cycle, protein degradation and cytoskeletal reorganization. In multiple myeloma, there is an overexpression of DAC proteins. Panobinostat inhibits class I (HDACs 1, 2, 3, 8), class II (HDACs 4, 5, 6, 7, 9, 10) and class IV (HDAC 11) proteins. Panobinostat's antitumor activity is believed to be attributed to epigenetic modulation of gene expression and inhibition of protein metabolism. Panobinostat also exhibits cytotoxic synergy with bortezomib, a proteasome inhibitor concurrently used in treatment of multiple myeloma.
Pharmacokinetics
- Absorption
- After a 20 mg dose, panobinostat was quickly absorbed with a time to maximum absorption of 2 hours.
- Distribution
- Metabolism
- Panobinostat was extensively metabolized to 77 metabolites. Unchanged panobinostat recovered in urine and feces was 2% and 3%, respectively. Primary metabolic pathways of panobinostat are reduction, hydrolysis, oxidation, and glucuronidation processes. CYP and non-CYP enzymes were found to play significant role in metabolism, CYP2D6 and CYP2C19 playing minor roles.
- Elimination
Toxicity
Farydak carries a Boxed Warning alerting patients and health care professionals that severe diarrhea and severe and fatal cardiac events, arrhythmias and electrocardiogram (ECG) changes have occurred in patients receiving Farydak. Because of these risks, Farydak is being approved with a Risk Evaluation and Mitigation Strategy (REMS) consisting of a communication plan to inform health care professionals of these risks and how to minimize them.
Active Ingredient/Synonyms
(2E)-N-hydroxy-3-[4-({[2-(2-methyl-1H-indol-3-yl)ethyl]amino}methyl)phenyl]acrylamide | panobinostat | Panobinostat |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.