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Trametinib

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Information about Trametinib

Trametinib is a dual-kinase inhibitor that is used in the treatment of advanced malignant melanoma, usually in combination with darbafenib.

Trametinib
Trametinib

Liver safety of Trametinib

Trametinib therapy is associated with transient elevations in serum aminotransferase and alkaline phosphatase levels during therapy, but has yet to be linked cases of clinically apparent acute liver injury

Mechanism of action of Trametinib

Trametinib (tra me’ ti nib) is an orally available, small molecule inhibitor of the mitogen activated extracellular signal regulated kinases 1 and 2 (MEK1 and MEK2), which are important components of the kinase cascade in the mitogen activated protein kinase (MAPK) pathway (RAS-RAF-MEK-ERK).  Components of the MAPK pathway are frequently mutated in patients with malignant melanoma, particular the RAF isoform BRAF.  These mutations cause a constitutive activation of the MAPK pathway, resulting in unregulated cell growth and proliferation.  Clinical trials of trametinib in patients with metastatic malignant melanoma have shown that it prolongs progression free and overall survival, but the effect seemed to be limited to patients with the BRAF mutations. 

FDA approval information for Trametinib

Trametinib was approved for use in the United States in 2013. Indications are for therapy of unresectable or metastatic malignant melanoma, non-small cell lung cancer (NSCLC) and anaplastic thyroid cancer with BRAF V600E or V600K mutations either alone or in combination with dabrafenib (a BRAF kinase inhibitor). 

Dosage and administration for Trametinib

Trametinib is available in tablets of 0.5 and 2.0 mg under the brand name Mekinist. The typical dose is 2 mg orally once daily. 

Side effects of Trametinib

Common side effects include skin rash (57%), diarrhea (43%), fatigue (26%), peripheral edema (21%), and hypertension (15%).  Uncommon, but potentially severe adverse reactions include cardiomyopathy, interstitial pneumonitis, colitis, intestinal perforation, hemorrhage, thromboembolism, new primary malignancies, ocular toxicity, retinal vein occlusion, severe skin reactions and embryonal-fetal toxicity.

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