Product Information
Registration Status: ActiveIBRANCE CAPSULE 125mg is approved to be sold in Singapore with effective from 2016-07-21. It is marketed by PFIZER PTE LTD, with the registration number of SIN15050P.
This product contains Palbociclib 125mg in the form of CAPSULE. It is approved for ORAL use.
This product is manufactured by Pfizer Manufacturing Deutschland GmbH in GERMANY.
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
Palbociclib is an oral, reversible, selective, small-molecule inhibitor of CDK4 and CDK6 indicated in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. CDK4 and CDK6 along with their regulatory partner cyclin D1 play a key role in regulating the G1- to S-phase cell-cycle transition via regulation of phosphorylation of the retinoblastoma (Rb) protein. Inhibition of these proteins leads to reduced phosphorylation of Rb, inhibition of downstream signalling, and increased tumor growth arrest. Palbociclib received an accelerated approval from the Food and Drug Administration on February 3, 2015.
Indication
Palbociclib is indicated in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. This indication is approved under accelerated approval based on progression-free survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Mechanism of Action
Palbociclib is an oral, reversible, selective, small-molecule inhibitor of CDK4 and CDK6. CDK4 and CDK6 along with their regulatory partner cyclin D1 play a key role in regulating the G1- to S-phase cell-cycle transition via regulation of phosphorylation of the retinoblastoma (Rb) protein.
Pharmacokinetics
- Absorption
- The mean Cmax of palbociclib is generally observed between 6 to 12 hours (time to reach maximum concentration, Tmax) following oral administration. The mean absolute bioavailability after an oral 125 mg dose is 46%.
- Distribution
- The mean apparent distribution of palbociclib is 2583 L, suggesting that palbociclib penetrates extensively into peripheral tissues.
- Metabolism
- The primary metabolic pathways for palbociclib involve oxidation and sulfonation, with acylation and glucuronidation contributing as minor pathways. Palbociclib is the major circulating drug-derived entity in plasma (23%). The major circulating metabolite was found to be a glucuronide conjugate of palbociclib, although it only represented 1.5% of the administered dose in the excreta.
- Elimination
Clearance
63.1 L/hr
Active Ingredient/Synonyms
6-acetyl-8-cyclopentyl-5-methyl-2-{[5-(piperazin-1-yl)pyridin-2-yl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one | Palbociclib |
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.