"The U.S. Food and Drug Administration today approved two new drugs, Tafinlar (dabrafenib) and Mekinist (trametinib), for patients with advanced (metastatic) or unresectable (cannot be removed by surgery) melanoma, the most dangerous type of skin "...
- Clinician Information:
Mekinist Side Effects Center
Medical Editor: John P. Cunha, DO, FACOEP
Mekinist (trametinib) is a kinase inhibitor used to treat patients with melanoma with BRAF V600E or V600K mutations that are metastatic or unable to be removed by surgery (unresectable). Common side effects include acne, rosacea, dry skin, itching, infection of the skin around a fingernail or toenail, diarrhea, inflammation of the lining of the mouth, abdominal pain, fluid retention and swelling of the limbs, high blood pressure, or bleeding.
The recommended dose of Mekinist is 2 mg orally once daily. Take at least 1 hour before or 2 hours after a meal. Mekinist may interact with other drugs. Tell your doctor all medications and supplements you use. Mekinist can cause fetal harm and is not recommended during pregnancy. Tell your doctor if you become pregnant during treatment. It is unknown if this drug is present in human milk. Because many drugs are present in human milk and because of the potential for serious adverse reactions in nursing infants, consult your doctor before breastfeeding.
Our Mekinist (trametinib) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
What is Prescribing information?
The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.
Mekinist FDA Prescribing Information: Side Effects
The following adverse reactions are discussed in greater detail in another section of the label:
- Cardiomyopathy [see WARNINGS AND PRECAUTIONS]
- Retinal pigment epithelial detachment [see WARNINGS AND PRECAUTIONS]
- Retinal vein occlusion [see WARNINGS AND PRECAUTIONS]
- Interstitial lung disease [see WARNINGS AND PRECAUTIONS]
- Serious skin toxicity [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The data described in the WARNINGS AND PRECAUTIONS section and below reflect exposure to MEKINIST in 329 patients including 107 (33%) exposed for greater than or equal to 6 months and 30 (9%) exposed for greater than or equal to one year. MEKINIST was studied in open-label single-arm trials (N = 118) or in an open-label, randomized, active-controlled trial (N = 211). The median age was 54, 60% were male, > 99% were white, and all patients had metastatic melanoma. All patients received 2 mg once daily doses of MEKINIST. The incidence of RPED and RVO are obtained from the 1,749 patients from all clinical trials with MEKINIST.
Table 2 presents adverse reactions identified from analyses of Trial 1, [see Clinical Studies] a randomized open-label trial of patients with BRAF V600E or V600K mutation-positive melanoma receiving MEKINIST (N = 211) 2 mg orally once daily or chemotherapy (N = 99) 2 2 [either dacarbazine 1,000 mg/m every 3 weeks or paclitaxel 175 mg/m every 3 weeks]. Patients with abnormal LVEF, history of acute coronary syndrome within 6 months, or current evidence of Class II or greater congestive heart failure (New York Heart Association) were excluded from Trial 1. The median duration of treatment with MEKINIST was 4.3 months. In Trial 1, 9% of patients receiving MEKINIST experienced adverse reactions resulting in permanent discontinuation of trial medication. The most common adverse reactions resulting in permanent discontinuation of MEKINIST were decreased left ventricular ejection fraction (LVEF), pneumonitis, renal failure, diarrhea, and rash. Adverse reactions led to dose reductions in 27% of patients treated with MEKINIST. Rash and decreased LVEF were the most common reasons cited for dose reductions of MEKINIST.
Table 2: Selected Adverse Reactions Occurring in ≥ 10%
of Patients Receiving MEKINIST and at a Higher Incidence than in the Control
(N = 211)
(N = 99)
|All Gradesb||Grades 3 and 4c||All Gradesb||Grades 3 and 4c|
|Skin and subcutaneous tissue disorders|
|Dermatitis acneiform||19||< 1||1||0|
|a Events included are higher in the trametinib
arm compared with chemotherapy by ≥ 5% in overall incidence or by ≥ 2%
Grade 3-4 adverse reactions higher in trametinib arm compared with
b National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.
c Grade 4 adverse reactions were limited to rash (n = 1) in trametinib arm and diarrhea (n = 1) in the chemotherapy arm.
d Includes the following terms: stomatitis, aphthous stomatitis, mouth ulceration, and mucosal inflammation.
e Includes the following terms: abdominal pain, abdominal pain lower, abdominal pain upper, and abdominal tenderness.
f Includes the following terms: lymphedema, edema, and peripheral edema.
g Includes the following terms: epistaxis, gingival bleeding, hematochezia, rectal hemorrhage, melena, vaginal hemorrhage, hemorrhoidal hemorrhage, hematuria, and conjunctival hemorrhage.
Other clinically important adverse reactions observed in < 10% of patients (N = 329) treated with MEKINIST were:
Nervous System Disorders: Dizziness, dysgeusia.
Ocular Disorders: Vision blurred, dry eye.
Cardiac Disorders: Bradycardia.
Gastrointestinal Disorders: Xerostomia.
Musculoskeletal and Connective Tissue Disorders: Rhabdomyolysis
Table 3: Percent-Patient Incidence of Laboratory
Abnormalities Occurring at a Higher Incidence in Patients Treated With MEKINIST
in Trial 1 [Between Arm Difference of ≥ 5% (All Grades) or ≥ 2%
(Grades 3 or 4)a]
(N = 211)
(N = 99)
|All Grades||Grades 3 and 4||All Grades||Grades 3 and 4|
|Increased Aspartate aminotransferase (AST)||60||2||16||1|
|Increased Alanine aminotransferase (ALT)||39||3||20||3|
|Increased Alkaline phosphatase||24||2||18||3|
|a No Grade 4 events were reported in either treatment arm.|
Read the entire FDA prescribing information for Mekinist (Trametinib Tablets) »
Additional Mekinist Information
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