Trametinib

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.

• MEKINIST 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.ICD-10: C43.9

• None. None.contraindicated

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. ( 2 ) 2.1 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 [see Clinical Studies (14.1, 14.2)] . 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 [see Clinical Studies (14.3)] . Information on FDA-approved tests for the detection of BRAF V600E mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics . ATC Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with MEKINIST and dabrafenib [see Clinical Studies (14.4)] . Information on FDA-approved tests for the detection of BRAF V600E mutations in ATC is available at: http://www.fda.gov/CompanionDiagnostics . Solid Tumors Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with MEKINIST and dabrafenib [see Clinical Studies (14.6)] . An FDA-approved test for the detection of BRAF V600E mutation in solid tumors other than melanoma and NSCLC is not currently available.

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. ( 5.1 ) Hemorrhage : Major hemorrhagic events can occur. Monitor for signs and symptoms of bleeding. ( 5.2 ) Colitis and Gastrointestinal Perforation : Colitis and gastrointestinal perforation can occur in patients receiving MEKINIST. ( 5.3 ) Venous Thromboembolic Events : Deep vein thrombosis (DVT) and pulmonary embolism (PE) can occur in patients receiving MEKINIST. ( 5.4 , 2.4 ) Cardiomyopathy : Assess left ventricular ejection fraction (LVEF) before treatment, after one month of treatment, then every 2 to 3 months thereafter. ( 5.5 , 2.4 ) Ocular Toxicities : Perform ophthalmological evaluation for any visual disturbances. For Retinal Vein Occlusion (RVO), permanently discontinue MEKINIST. ( 5.6 , 2.4 ) Interstitial Lung Disease (ILD)/Pneumonitis : Withhold MEKINIST for new or progressive unexplained pulmonary symptoms. Permanently discontinue MEKINIST for treatment-related ILD or pneumonitis. ( 5.7 , 2.4 ) Serious Febrile Reactions : Can occur when MEKINIST is used with dabrafenib. ( 5.8 , 2.4 ) Serious Skin Toxicities : Monitor for skin toxicities and for secondary infections. Permanently discontinue MEKINIST for intolerable Grade 2 or for Grade 3 or 4 rash not improving within 3 weeks despite interruption of MEKINIST. Permanently discontinue for severe cutaneous adverse reactions (SCARs).

The following clinically significant adverse reactions are described elsewhere in the labeling: New Primary Malignancies [see Warnings and Precautions ( 5.1)] Hemorrhage [see Warnings and Precautions (5.2)] Colitis and Gastrointestinal Perforation [see Warnings and Precautions (5.3)] Venous Thromboembolic Events [see Warnings and Precautions (5. 4 )] Cardiomyopathy [see Warnings and Precautions (5. 5 )] Ocular Toxicities [see Warnings and Precautions (5. 6 )] Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5. 7 )] Serious Febrile Reactions [see Warnings and Precautions (5. 8 )] Serious Skin Toxicities [see Warnings and Precautions (5. 9 )] Hyperglycemia [see Warnings and Precautions (5. 10 )] Hemophagocytic Lymphohistiocytosis [see Warnings and Precautions (5. 12 )] There are additional adverse reactions associated with dabrafenib. Refer to the dabrafenib prescribing information for additional information. Most common adverse reactions (≥ 20%) for MEKINIST as a single agent include rash, diarrhea, and lymphedema. ( 6.1 ) Most common adverse reactions (≥ 20%) for MEKINIST in combination with dabrafenib include: Unresectable or metastatic melanoma: pyrexia, nausea, rash, chills, diarrhea, vomiting, hypertension, and peripheral edema. ( 6.1 ) Adjuvant treatment of melanoma: pyrexia, fatigue, nausea, headache, rash, chills, diarrhea, vomiting, arthralgia, and myalgia. ( 6.1 ) NSCLC: pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea.

Lactation : Do not breastfeed. ( 8.2 ) Females and Males of Reproductive Potential : May impair fertility. Counsel patients on pregnancy planning and prevention. ( 8.3 ) 8.1 Pregnancy Risk Summary Based on its mechanism of action [see Clinical Pharmacology (12.1)] 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. Trametinib was embryotoxic and abortifacient in rabbits at doses greater than or equal to those resulting in exposures approximately 0.3 times the human exposure at the recommended adult clinical dose (see Data) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In reproductive toxicity studies, administration of trametinib to rats during the period of organogenesis resulted in decreased fetal weights at doses greater than or equal to 0.031 mg/kg/day [approximately 0.3 times the human exposure at the recommended adult dose based on area under the curve (AUC)].

Metabolism

The pharmacokinetics of trametinib were characterized following a single dose and multiple doses in patients with solid tumors and BRAF V600 mutation-positive metastatic melanoma. Following administration of MEKINIST tablets 0.125 mg (0.0625 times the approved recommended adult dosage) to 4 mg (2 times the approved recommended adult dosage) daily, both C max and AUC increase proportionally with dose.

The highest doses of MEKINIST evaluated in clinical trials were 4 mg orally once daily and 10 mg administered orally once daily on 2 consecutive days followed by 3 mg once daily. In seven patients treated on one of these two schedules, there were two cases of RPEDs for an incidence of 28%. Since trametinib is highly bound to plasma proteins, hemodialysis is likely to be ineffective in the treatment of overdose with MEKINIST.

• May 29, 2013NDANDA204114Novartis
• Mar 16, 2023NDANDA217513Novartis

1. 1Pyrexia4,00517%
2. 2Death3,37514%
3. 3Malignant Neoplasm Progression2,0138.5%
4. 4Rash1,7027.2%
5. 5Fatigue1,4956.3%
6. 6Nausea1,4656.2%
7. 7Chills1,2725.4%
8. 8Diarrhoea1,2635.3%
9. 9Product Use In Unapproved Indication1,0834.6%
10. 10Vomiting1,0504.4%
11. 11Off Label Use7713.3%
12. 12Headache7543.2%
13. 13Asthenia7193.0%
14. 14Drug Ineffective6512.7%
15. 15Malaise6512.7%

The 10 most recently updated of 302 ClinicalTrials.gov registrations naming Trametinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Testing Trametinib and Dabrafenib as a Potential Targeted Treatment in Cancers With BRAF Genetic Changes (MATCH-Subprotocol H)
  Active not recruiting · Phase 2 · Interventional · 44 enrolled · National Cancer Institute (NCI)
  NCT04439292updated 2026-06-12
• Nivolumab With Trametinib and Dabrafenib, or Encorafenib and Binimetinib in Treating Patients With BRAF Mutated Metastatic or Unresectable Stage III-IV Melanoma
  Active not recruiting · Phase 2 · Interventional · 52 enrolled · M.D. Anderson Cancer Center
  NCT02910700updated 2026-06-11
• Pediatric Long-Term Follow-up and Rollover Study
  Active not recruiting · Phase 4 · Interventional · 165 enrolled · Novartis Pharmaceuticals
  NCT03975829updated 2026-06-11
• Dabrafenib and/or Trametinib Rollover Study
  Recruiting · Phase 4 · Interventional · 100 enrolled · Novartis Pharmaceuticals
  NCT03340506updated 2026-06-10
• Rollover Study for Participants Who Have Been Treated With and Are Continuing to Benefit From Opnurasib as a Single Agent or in Combination With Other Study Treatments
  Recruiting · Phase 1 · Phase 2 · Interventional · 40 enrolled · Novartis Pharmaceuticals
  NCT07468071updated 2026-06-10
• Study of Efficacy and Safety of Dabrafenib in Combination With Trametinib in Previously Treated Patients With Metastatic, Radio-active Iodine Refractory BRAF V600E Mutation Positive Differentiated Thyroid Cancer
  Active not recruiting · Phase 3 · Interventional · 153 enrolled · Novartis Pharmaceuticals
  NCT04940052updated 2026-06-04
• Dabrafenib and Trametinib for BRAF V600 Mutant Low-Grade Gliomas
  Recruiting · Phase 2 · Interventional · 96 enrolled · University of California, San Francisco
  NCT07110246updated 2026-06-04
• Pan Tumor Rollover Study
  Recruiting · Phase 2 · Interventional · 1,500 enrolled · Bristol-Myers Squibb
  NCT03899155updated 2026-06-03
• Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
  Active not recruiting · Phase 2 · Interventional · 6,452 enrolled · National Cancer Institute (NCI)
  NCT02465060updated 2026-06-03
• Testing Dabrafenib and Trametinib With or Without Hydroxychloroquine in Stage IIIC or IV BRAF V600E/K Melanoma
  Terminated · Phase 2 · Interventional · 5 enrolled · ECOG-ACRIN Cancer Research Group
  NCT04527549updated 2026-06-01

CPIC-curated drug–gene pairs for Trametinib. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

• G6PDCPIC C
  G6PD

Frequently asked questions

How does Trametinib work?

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.

What is Trametinib used for?

According to FDA labeling, Trametinib carries indications including: MEKINIST 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Trametinib?

Trametinib is classified as Mitogen-activated protein kinase (MEK) inhibitors, Kinase Inhibitor, Protein Kinase Inhibitors, Cellular Proliferation Alteration.

What are the brand names for Trametinib?

Trametinib is marketed under brand names including Mekinist.

What are the contraindications for Trametinib?

Trametinib labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.