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Mekinist

trametinib
MEK Inhibitor Novartis FDA Approved 2013
Indications Dosing Forms Contraindications Warnings Adverse Reactions Pharmacology Clinical Studies Tumor Types
1. Indications and Usage

Used in combination with dabrafenib for all dabrafenib indications: unresectable/metastatic melanoma BRAF V600E/K, adjuvant melanoma BRAF V600E/K, metastatic NSCLC BRAF V600E, anaplastic thyroid BRAF V600E, BRAF V600E solid tumors, pediatric low-grade glioma BRAF V600E.

2. Dosage and Administration

2 mg orally once daily (in combination with dabrafenib 150 mg BID)
Take on empty stomach: at least 1 hour before or 2 hours after meal
Dose reductions: 1.5 mg once daily, then 1 mg once daily

3. Dosage Forms and Strengths

Tablets: 0.5 mg, 2 mg

4. Contraindications

None listed.

5. Warnings and Precautions
  • Cardiomyopathy: Decreased LVEF in 11% (with dabrafenib). Assess LVEF before treatment, after 1 month, and every 2-3 months thereafter.
  • Retinal Pigment Epithelial Detachment (RPED): In 2%. Including retinal vein occlusion. Ophthalmologic exam at baseline and for visual symptoms.
  • Hemorrhage: Major hemorrhage in 5%. Including intracranial and GI.
  • Venous Thromboembolism: DVT/PE in 6% (with dabrafenib).
  • Interstitial Lung Disease/Pneumonitis: In 2%.
  • Serious Skin Toxicity: SJS/TEN reported (rare). Rash in 24%.
  • Rhabdomyolysis: Monitor CK and creatinine if myalgia is significant.
  • Embryo-Fetal Toxicity
6. Adverse Reactions
Most Common Adverse Reactions

Pyrexia (57%, with dabrafenib), rash (24%), diarrhea (20%), fatigue (38%), nausea (35%), peripheral edema (15%), acneiform dermatitis (11%), dry skin (9%), chills (24%), hypertension (14%)

Fatigue
38%
Nausea
35%
Rash
24%
Chills
24%
Diarrhea
20%
Peripheral Edema
15%
Hypertension
14%
Acneiform Dermatitis
11%
Dry Skin
9%

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

12. Clinical Pharmacology
Mechanism of Action

Trametinib is a reversible, allosteric inhibitor of MEK1 and MEK2 (mitogen-activated extracellular signal regulated kinase). It inhibits MEK activation and MEK kinase activity, blocking downstream ERK phosphorylation. Combined BRAF and MEK inhibition (dabrafenib + trametinib) provides more complete blockade of the MAPK pathway than either agent alone, delays development of resistance, and paradoxically reduces the incidence of cutaneous SCC seen with BRAF inhibitor monotherapy.

Pharmacokinetics

Tmax: 1.5 hours. Half-life: approximately 3.9-4.8 days. Protein binding: 97.4%. Metabolized via deacetylation (non-CYP). Steady-state by Day 15. Excreted in feces (≥80%) and urine (≤20%). Food reduces AUC by ~24%.

14. Clinical Studies

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

Pivotal Clinical Trials
Additional Resources
📋 All Trametinib Trials on ClinicalTrials.gov ↗ 📚 PubMed: Trametinib Clinical Trials ↗
Approved Tumor Types
Melanoma Lung Cancer Thyroid Cancer