Drug information of trametinib

trametinib


Mechanism of effect

Trametinib reversibly and selectively inhibits mitogen-activated extracellular kinase (MEK) 1 and 2 activation and kinase activity. MEK is a downstream effector of the protein kinase B-raf (BRAF); BRAF V600 mutations result in constitutive activation of the BRAF pathway (including MEK1 and MEK2). Through inhibition of MEK 1 and 2 kinase activity, trametinib causes decreased cellular proliferation, cell cycle arrest, and increased apoptosis . The combination of trametinib and dabrafenib allows for greater inhibition of the MAPK pathway, resulting in BRAF V600 melanoma cell death. Trametinib plus dabrafenib has been reported to synergistically inhibit cell growth in lung cancer cell lines which are BRAF V600E-mutant.

Pharmacokinetics

Absorption:

Rapid; decreased with a high-fat, high-calorie meal (~1,000 calories)

Distribution:

214 L

Metabolism:

Predominantly deacetylation (via hydrolytic enzymes) alone or with mono-oxygenation or in combination with glucuronidation

Excretion:

Feces (>80%); urine (<20% with <0.1% as unchanged drug)

Time to Peak:

1.5 hours; delayed with a high-fat, high-calorie meal (~1,000 calories)

Half-Life Elimination:

~4 to 5 days

Protein Binding:

~97% to plasma proteins

Points of recommendation

Tell your doctor if you have ever had:

  • heart disease, high blood pressure;
  • diabetes;
  • lung disease;
  • liver or kidney disease;
  • a stomach or intestinal disorder;
  • eye problems (especially a problem with your retina); or
  • bleeding problems, or a blood clot.

Using trametinib with dabrafenib may increase your risk of developing a certain type of skin cancer. Ask your doctor about your specific risk. Tell your doctor if you notice any new skin symptoms such as redness, warts, sores that will not heal, or a mole that has changed in size or color.

Trametinib can harm an unborn baby or cause birth defects if the mother or the father is using trametinib.

If you are a woman, do not use trametinib if you are pregnant. You may need to have a negative pregnancy test before starting this treatment. Use effective birth control to prevent pregnancy while you are using this medicine and for at least 4 months after your last dose.

If you are a man, use effective birth control if your sex partner is able to get pregnant, even if you have had a vasectomy. Keep using birth control for at least 4 months after your last dose.

This medicine may affect fertility (ability to have children) in women. However, it is important to use birth control to prevent pregnancy because trametinib can harm an unborn baby.

You should not breastfeed while using this medicine, and for at least 4 months after your last dose.

Pregnancy level

 


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