Overview
11 DESCRIPTION Trametinib dimethyl sulfoxide is a kinase inhibitor. The chemical name is acetamide, N-[3-[3-cyclopropyl-5-[(2-fluoro-4- iodophenyl)amino]-3,4,6,7-tetrahydro-6,8-dimethyl- 2,4,7-trioxopyrido[4,3-d]pyrimidin-1(2H)-yl]phenyl]-, compound with 1,1’-sulfinylbis[methane] (1:1). It has a molecular formula C 26 H 23 FIN 5 O 4 •C 2 H 6 OS with a molecular mass of 693.53 g/mol.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 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
- 1 INDICATIONS AND USAGE 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. ( 1.1 , 2.
Common Doses
- 2 mg
- 1 mg
- 1.5 mg
- 0.3 mg
Dosage
2 DOSAGE AND ADMINISTRATION 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 .
Contraindications
- 4 CONTRAINDICATIONS None. None. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS 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.
Interactions
- 7 DRUG INTERACTIONS MEKINIST is indicated for use in combination with dabrafenib. Refer to the dabrafenib prescribing information for additional risk information that applies to combination use treatment.