Trametinib

Action and Spectrum

Cell surface receptors and intracellular downstream signalling molecules are triggered by the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases (ERK) pathway.s 

A serine/threonine kinase called RAF is activated by activated RAS protein, and it turn stimulates mitogen-activated extracellular signal-regulated kinase 1 (MEK1) and MEK2, among other downstream proteins. 

Drug Interaction

Adverse Reaction

Frequency defined: 

>20-10% 

Hypertension (15%) 

Acneiform eruption (19%) 

Hypoalbuminemia (42%) 

Skin rash (57%) 

Abdominal pain (13%) 

Stomatitis (15%) 

Diarrhea (43%) 

Anemia (38%) 

1-10% 

Pruritis 

Dysgeusia 

Dizziness 

Pneumonitis (<2%) 

Dry eye syndrome 

Frequency not defined:  

Decreased left ventricular ejection fraction 

Retinal detachment 

Renal failure 

Black Box Warning

None 

Contraindication / Caution

Contraindication: 

None 

Caution: 

New primary malignancies  

Hemorrhage 

Colitis and gastrointestinal (GI) perforation 

Cardiomyopathy 

Ocular toxicity 

Pregnancy / Lactation

Pregnancy consideration: Based on animal studies, trametinib is assigned under pregnancy category C. 

Lactation: No data available for excretion in breast milk, it should be avoided due to potential side effects. 

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no evidence of risk to the fetus in the first trimester or the later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits. These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Trametinib stops the growth of certain tumors that have a BRAF V600 mutation both in vitro and in vivo. 

It has been determined that one mechanism of intrinsic resistance to BRAF inhibitors in BRAF-mutant colorectal cancer is the promotion of EGFR-mediated MAPK pathway re-activation. 

Trametinib inhibits the catalytic activity of MEKs by displaying a high affinity for unphosphorylated MEK1 and MEK2. 

Adminstartion

Tablet should be taken on an empty stomach at least one hour before or two hours after eating. 

Swallow whole, do not crush or break 

Use a feeding tube or oral dosage syringe to administer. 

Take on an empty stomach or with a low-fat meal. 

For missed doses: 

Take it as soon as you can if it is more than 12 hours before your next regular dose. 

Less than 12 hours prior to your next dose: Skip the missed dose and give the next one at the scheduled time. 

Patient Information Leaflet

Patient Information Leaflet   

Generic Name: trametinib (Rx)   

Pronounced: tra-ME-ti-nib 

Why do we use trametinib? 

Patients with unresectable or metastatic melanoma who have not yet received BRAF-inhibitor treatment indicated with trametinib as a monotherapy. 

It is used in combination with dabrafenib to treat individuals with BRAF V600E mutation-related metastatic non-small cell lung cancer (NSCLC).  

Patients with locally advanced or metastatic anaplastic thyroid carcinoma (ATC) who have no viable locoregional therapeutic alternatives are treated with in combination with dabrafenib.