Trametinib

What it is and how it works

Mechanism of Action Trametinib is a reversible inhibitor of mitogen-activated extracellular signal-regulated kinase 1 (MEK1) and MEK2 activation and of MEK1 and MEK2 kinase activity. MEK proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway, which promotes cellular proliferation. BRAF V600E mutations result in constitutive activation of the BRAF pathway which includes MEK1 and MEK2. Trametinib inhibits cell growth of various BRAF V600 mutation-positive tumors in vitro and in vivo. Trametinib and dabrafenib target two different kinases in the RAS/RAF/MEK/ERK pathway.

Indications

is a kinase inhibitor indicated as a single agent for the treatment of BRAF-inhibitor treatment-naïve patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test. ( 1.1 , 2.1 ) MEKINIST is indicated, in combination with dabrafenib, for: the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test. ( 1.1 , 2.1 ) the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection. ( 1.2 , 2.1 ) the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test. ( 1.3 , 2.1 ) the treatment of patients with locally advanced or metastatic anaplastic thyroid cancer (ATC) with BRAF V600E mutation, as detected by an FDA-approved test, and with no satisfactory locoregional treatment options.

Dosage and administration (summary)

The recommended dosage of MEKINIST in adult patients is 2 mg orally once daily. The recommended dosage for MEKINIST in pediatric patients is based on body weight. Patient Selection Melanoma Confirm the presence of BRAF V600E or V600K mutation in tumor specimens prior to initiation of treatment with MEKINIST as a single agent or in combination with dabrafenib . Information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics . NSCLC Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with MEKINIST and dabrafenib .

Contraindications

None. None.

Warnings and precautions

New Primary Malignancies, Cutaneous and Non-Cutaneous : Can occur when MEKINIST is used with dabrafenib. Monitor patients for new malignancies prior to, or while on therapy, and following discontinuation of treatment. Hemorrhage : Major hemorrhagic events can occur. Monitor for signs and symptoms of bleeding. Colitis and Gastrointestinal Perforation : Colitis and gastrointestinal perforation can occur in patients receiving MEKINIST. Venous Thromboembolic Events : Deep vein thrombosis (DVT) and pulmonary embolism (PE) can occur in patients receiving MEKINIST.

Pregnancy

Pregnancy Risk Summary Based on its mechanism of action and findings from animal reproduction studies, MEKINIST can cause fetal harm when administered to a pregnant woman. There is insufficient data in pregnant women exposed to MEKINIST to assess the risks.

Storage and supply

Tablets : 0.5 mg tablets: Yellow, ovaloid, biconvex, unscored film-coated tablets with beveled edges and with the Novartis logo debossed on one side and ‘TT’ on the other side; available in bottles of 30 (NDC 0078-1105-15).

Source: Trametinib (Mekinist) — US FDA prescribing information, 2026-05-07, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.