COTELLIC FILM-COATED TABLET 20mg

Cobimetinib

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.

Active Ingredient / Synonyms

Cobimetinib | Cobimetinib |

Description

Cobimetinib is an orally active, potent and highly selective small molecule inhibiting mitogen-activated protein kinase kinase 1 (MAP2K1 or MEK1), and central components of the RAS/RAF/MEK/ERK signal transduction pathway. It has been approved in Switzerland and the US, in combination with vemurafenib for the treatment of patients with unresectable or metastatic BRAF V600 mutation-positive melanoma.

Indication

For the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation. Cobimetinib is used in combination with vemurafenib, a BRAF inhibitor.

Mechanism of Action

MEK inhibitor Cobimetinib specifically binds to and inhibits the catalytic activity of MEK1, resulting in inhibition of extracellular signal-related kinase 2 (ERK2) phosphorylation and activation and decreased tumor cell proliferation. Cobimetinib and vemurafenib target two different kinases in the RAS/RAF/MEK/ERK pathway.

Pharmacodynamics

Cobimetinib is a reversible inhibitor of mitogen-activated protein kinase 1 (MAPK)/extracellular signal regulated kinase 1 (MEK1) and MEK2. Preclinical studies have demonstrated that this agent is effective in inhibiting the growth of tumor cells bearing a BRAF mutation, which has been found to be associated with many tumor types. A threonine-tyrosine kinase and a key component of the RAS/RAF/MEK/ERK signalling pathway that is frequently activated in human tumors, MEK1 is required for the transmission of growth-promoting signals from numerous receptor tyrosine kinases. Cobimetinib is used in combination with vemurafenib because the clinical benefit of a BRAF inhibitor is limited by intrinsic and acquired resistance. Reactivation of the MAPK pathway is a major contributor to treatment failure in BRAF-mutant melanomas, approximately ~80% of melanoma tumors becomes BRAF-inhibitor resistant due to reactivation of MAPK signalling. BRAF-inhibitor resistant tumor cells are sensitive to MEK inhibition, therefore cobimetinib and vemurafenib will result in dual inhibition of BRAF and its downstream target, MEK.

Pharmacokinetics

Absorption:

The bioavailability of cobimetinib is 46%, the AUC and Cmax is unaffected by food.

Distribution:

806L in cancer patients based on a population PK analysis.

Metabolism:

Cobimetinib is mainly metabolized via CYP3A oxidation and UGT2B7 glucuronidation with no major metabolites formed.

Elimination:

76% of the dose was recovered in feces with 6.6% as unchanged drug. 17.8% of the dose was recovered in urine with 1.6% as unchanged drug.

Half-life

Average half life was 44 hours.

Clearance

13.9L/h

Toxicity

The most common adverse effects (>20%) for cobimetinib are diarrhea, photosensitivity reactions, nausea, fever and vomiting.

References

  1. Health Science Authority of Singapore - Reclassified POM
  2. Drugbank

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Approval Information

COTELLIC FILM-COATED TABLET 20mg was registered with Health Science Authority of Singapore by ROCHE SINGAPORE PTE LTD. It is marketed with the registration number of SIN15219P with effective from 2017-04-21.

This product contains 20mg of Cobimetinib in the form of TABLET, FILM-COATED.

The medicine was manufactured by F. Hoffmann-La Roche Ltd in SWITZERLAND, and Roche S.p.A. (Primary & Secondary Packager) in ITALY

It is a Presciption Only Medicine which can only be obtained from a doctor or a dentist, or from a pharmacist with a prescription from a Singapore-registered doctor or dentist.

Anatomical Therapeutic Chemical (ATC) Classification

ATC Code: L01XE38

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