Trametinib

Trametinib Uses, Dosage, Side Effects, Food Interaction and all others data.

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 .

The U.S. Food and Drug Administration approved Dabrafenib(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) .

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 .

Trametinib
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Trametinib
Availability	Prescription only
Generic	Trametinib
Trametinib Other Names	Tramétinib, Trametinib, Trametinibum
Related Drugs	Opdivo, methotrexate, Keytruda, Armour Thyroid, hydroxyurea, pembrolizumab, doxorubicin, cisplatin, Tagrisso, Avastin
Weight	0.5mg, 2mg
Type	Oral tablet
Formula	C₂₆H₂₃FIN₅O₄
Weight	Average: 615.3948 Monoisotopic: 615.077875874
Protein binding	97.4% bound to human plasma proteins
Groups	Approved
Therapeutic Class
Manufacturer
Available Country	United States
Last Updated:	September 19, 2023 at 7:00 am

Uses

Trametinib is a kinase inhibitor used to treat patients with specific types of melanoma, non-small cell lung cancer, and thyroid cancer.

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 Dabrafenib for the treatment of treat anaplastic thyroid cancer caused by an abnormal BRAF V600E gene .

Trametinib is also used to associated treatment for these conditions: Metastatic Melanoma, Unresectable Melanoma

How Trametinib works

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 .

Toxicity

Most common adverse reactions (≥20%) for trametinib include rash, diarrhea, and lymphedema .

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 .

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 .

Hemorrhage: Major hemorrhagic events can occur in patients receiving TAFINLAR in combination with trametinib. Monitor for signs and symptoms of bleeding .

Venous Thromboembolism: Deep vein thrombosis and pulmonary embolism can occur in patients receiving the drug combination .

Cardiomyopathy: Assess LVEF before treatment with TAFINLAR in combination with trametinib, after one month of treatment, then every 2 to 3 months thereafter .

Ocular toxicities: Perform an ophthalmologic evaluation for any visual disturbances .

Serious Febrile Reactions: Incidence and severity of pyrexia are increased with TAFINLAR in combination with trametinib .

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 .

Hyperglycemia: Monitor serum glucose levels in patients with pre-existing diabetes or hyperglycemia .

Glucose-6-Phosphate Dehydrogenase Deficiency: Closely monitor for hemolytic anemia .

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 .

Food Interaction

Take separate from meals. Take at least one hour before or two hours after a meal.

[Moderate] ADJUST DOSING INTERVAL: Food may reduce as well as delay the absorption of trametinib.

In study subjects, administration of a single dose of trametinib with a high-fat, high-calorie meal decreased peak plasma concentration (Cmax) and systemic exposure (AUC) by 70% and 24%, respectively, and delayed Tmax by approximately 4 hours compared to administration in the fasted state.

MANAGEMENT: Trametinib should be taken at least 1 hour before or 2 hours after a meal.

Trametinib Disease Interaction

Moderate: lung toxicity, cardiomyopathy, GI perforation, hemorrhage, hepatic impairment, hyperglycemia, ocular toxicities, renal impairment, venous thromboembolism

Volume of Distribution

Apparent volume of distribution (Vd/F) = 214 L

Elimination Route

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 .