Source of information: Drugbank (External Link). Last updated on: 3rd July 18
*Trade Name used in the content below may not be the same as the HSA-registered product.
Active Ingredient / Synonyms
Tramétinib | Trametinib | Trametinibum | Trametinib |
Trametinib dimethyl sulfoxide is a kinase inhibitor. Each 1-mg tablet contains 1.127 mg trametinib dimethyl sulfoxide equivalent to 1 mg of trametinib non-solvated parent. FDA approved on May 29, 2013 [L2727]. The U.S. Food and Drug Administration approved [DB08912](Tafilnar) and Mekinist (trametinib), administered together, for the treatment of anaplastic thyroid cancer (ATC) that cannot be removed by surgery or has spread to other parts of the body (metastatic), and has a type of abnormal gene, BRAF V600E (BRAF V600E mutation-positive) [L2726]. Thyroid cancer is a disease in which cancer cells form in the tissues of the thyroid. Anaplastic thyroid cancer is a rare, aggressive type of thyroid cancer. The National Institutes of Health (NIH) estimates there will be 53,990 new cases of thyroid cancer and an estimated 2,060 deaths from the disease in the United States in 2018. Anaplastic thyroid cancer accounts for approximately 1 to 2 percent of all thyroid cancers [L2726].
Trametinib is indicated for the treatment of unresectable or metastatic melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test [FDA]. In May 2018, it was approved for use with [DB08912] for the treatment of treat anaplastic thyroid cancer caused by an abnormal BRAF V600E gene [L2726].
Mechanism of Action
Trametinib is a reversible, allosteric 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. Trametinib helps with melanoma with the BRAF V600E or V600K as the mutation results in the constitutive activation of the BRAF pathway which includes MEK1 and MEK2 [FDA label].
Trametinib is an anticancer agent which causes apoptosis (or programmed cell death) and inhibits cell proliferation, which are both important in the treatment of malignancies [A32984].
Trametinib is readily absorbed. When an oral administration of trametinib was given to patients with BRAF V600 mutation-positive melanoma, peak plasma concentration occurred 1.5 hours post-dose (Tmax). A single 2 mg oral dose has a bioavailability of 72%. When a dose of 2mg/day is given, the peak plasma concentration (Cmax) is 22.2 ng/mL [FDA label].
Apparent volume of distribution (Vd/F) = 214 L [FDA label]
Trametinib is metabolized predominantly via deacetylation alone or with mono-oxygenation or in combination with glucuronidation biotransformation pathways in vitro. Deacetylation is likely mediated by hydrolytic enzymes, such as carboxyl-esterases or amidases. The cytochrome P450 enzyme system is not involved with the metabolism of trametinib. The predominant circulating component in the plasma is the parent drug [FDA label].
80% of the dose is excreted in the feces. <20% of the dose is excreted in the urine with <0.1% of the excreted dose in the form of the parent compound [FDA label].
Elimination half-life = 3.9-4.8 days [FDA label].
Apparent clearance = 4.9 L/h [FDA label]
Most common adverse reactions (≥20%) for trametinib include rash, diarrhea, and lymphedema [FDA label]. The most common adverse reactions (≥20%) for Tafinlar in combination with Trametinib are pyrexia, chills, fatigue, rash, nausea, vomiting, diarrhea, abdominal pain, peripheral edema, cough, headache, arthralgia, night sweats, decreased appetite, constipation, and myalgia [FDA Label]. The following is a list of toxicities that may occur with the combination of Dabrafenib and Trametinib: **New primary malignancies**: These may occur when Tafinlar is administered as a single agent or in combination with Trametinib. Monitor patients for new malignancies prior to initiation of therapy, while on therapy, and following discontinuation of TAFINLAR or the combination therapy. Tumor Promotion in BRAF Wild-Type Melanoma: Increased cell proliferation can occur with BRAF inhibitors [FDA Label]. **Hemorrhage**: Major hemorrhagic events can occur in patients receiving TAFINLAR in combination with trametinib. Monitor for signs and symptoms of bleeding [FDA Label]. **Venous Thromboembolism**: Deep vein thrombosis and pulmonary embolism can occur in patients receiving the drug combination [FDA Label]. **Cardiomyopathy**: Assess LVEF before treatment with TAFINLAR in combination with trametinib, after one month of treatment, then every 2 to 3 months thereafter [FDA Label]. **Ocular toxicities**: Perform an ophthalmologic evaluation for any visual disturbances [FDA Label]. **Serious Febrile Reactions**: Incidence and severity of pyrexia are increased with TAFINLAR in combination with trametinib [FDA Label]. **Serious Skin Toxicity**: Monitor for skin toxicities and for secondary infections. Discontinue for intolerable Grade 2, or Grade 3 or 4 rash not improving within 3 weeks despite the interruption of TAFINLAR [FDA Label]. **Hyperglycemia**: Monitor serum glucose levels in patients with pre-existing diabetes or hyperglycemia [FDA Label]. **Glucose-6-Phosphate Dehydrogenase Deficiency**: Closely monitor for hemolytic anemia [FDA Label]. **Embryofetal Toxicity**: Can cause fetal harm. Advise females of reproductive potential of potential risk to a fetus. TAFINLAR may render hormonal contraceptives less effective and an alternative method of contraception should be used [FDA Label].
Although best effort has been made to ensure the information provided is correct and updated, users are advised to visit HSA Official website whenever in doubt. Please see Disclaimers.
We welcome all the content error reporting/feedback. Please contact us @ Text Us!