Genetic Implications:
Pronunciation:
tra-me-ti-nib
Trade Name(s)
Ther. Class.
Pharm. Class.
kinase inhibitors
Inhibits the activity of kinases, enzymes that promote cellular proliferation.
Therapeutic Effect(s):
Absorption: Well absorbed following oral administration.
Distribution: Unknown.
Protein Binding: 97.4%.
Metabolism and Excretion: 50% metabolized, 80% eliminated in feces (metabolites and parent compound), 20% excreted in urine (mostly as metabolites).
Half-life: 3.9–4.8 days.
TIME/ACTION PROFILE (response)
ROUTE | ONSET | PEAK | DURATION |
---|---|---|---|
PO | 1 mo | 2 mo | 5–7 mo |
Contraindicated in:
Use Cautiously in:
CNS: INTRACRANIAL HEMORRHAGE, dizziness, dysgeusia
CV: CARDIOMYOPATHY, VENOUS THROMBOEMBOLISM, hypertension
Derm: acneiform dermatitis, rash, skin toxicity, basal cell carcinoma, cellulitis, cutaneous squamous cell carcinoma, dry skin, erythema, folliculitis, palmar-plantar erythrodysesthesia syndrome, melanoma, paronychia, pruritus
EENT: blurred vision, dry eyes, retinal pigment epithelial detachment, retinal vein occlusion
Endo: hyperglycemia
GI: GI HEMORRHAGE, GI PERFORATION, abdominal pain, diarrhea, ↑ liver enzymes, stomatitis, colitis
GU: ↓ fertility (females)
Hemat: BLEEDING
MS: rhabdomyolysis
Resp: INTERSTITIAL LUNG DISEASE
Misc: MALIGNANCY, fever (including serious febrile reactions) , lymphedema
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
Drug-Drug
None noted
Treatment of Unresectable/Metastatic Melanoma, NSCLC, or Anaplastic Thyroid Cancer
PO (Adults): 2 mg once daily; continue until disease progression or unacceptable toxicity.
Adjuvant Treatment of Unresectable/Metastatic Melanoma
PO (Adults): 2 mg once daily; continue until disease progression or unacceptable toxicity for up to 1 yr.
Tablets: 0.5 mg, 2 mg
Assess left ventricular ejection fraction (LVEF) by echocardiogram or multigated acquisition (MUGA) scan before starting, after 1 month, and at 2–3 mo intervals during therapy. If asymptomatic and absolute ↓ LVEF of ≥10% from baseline and below institutional lower limits of normal from pretreatment value, withhold for up to 4 wks. If LVEF improves to normal within 4 wks, resume trametinib at lower dose, ↓ by 0.5 mg, or discontinue in patients taking 1 mg daily. If symptomatic HF, absolute ↓ LVEF >20% of baseline that is below institutional lower limits of normal, or absolute ↓ LVEF ≥10% of baseline that is below institutional lower limits of normal that does not improve to normal within 4 wks following interruption of therapy, permanently discontinue trametinib.
Assess for signs and symptoms of interstitial lung disease (cough, dyspnea, hypoxia, pleural effusion, infiltrates). Permanently discontinue trametinib if these occur.
Monitor for signs and symptoms venous thromboembolism (shortness of breath, chest pain, arm or leg swelling). Permanently discontinue trametinib and dabrafenib for life threatening pulmonary embolism. Withhold trametinib for uncomplicated deep vein thrombosis or pulmonary embolism for up to 3 wks; if improved to Grade 0–1, trametinib may be resumed at lower dose level. Do not modify dose of dabrafenib.
Monitor for signs and symptoms of hemorrhage. Withhold trametinib for Grade 3 hemorrhagic events; if improved, resume at next lower dose level. Permanently discontinue therapy for all Grade 4 hemorrhagic events and for any Grade 3 hemorrhagic events that do not improve.
Monitor for signs and symptoms of colitis and GI perforation.
Lab Test Considerations:
Confirm presence of BRAF V600E or V600K mutation in tumor specimens prior to starting therapy with trametinib. Information on FDA-approved tests for the detection of BRAF V600E mutations in melanoma or NSCLC is available at: http://www.fda.gov/CompanionDiagnostics.
Inform patient of potential side effects. Advise patient to notify health care professional if signs and symptoms of heart failure (pounding or racing heart, shortness of breath, swelling of feet or ankles, lightheadedness), visual disturbances (blurred vision, loss of vision, seeing colored dots, seeing a blurred outline or halo around objects, other visual changes), dyspnea, progressive or intolerable rash (acne; redness, swelling, peeling, or tenderness of hands or feet), hypertension (severe headache, lightheadedness, dizziness), bleeding problems (headaches, dizziness, or feeling weak, coughing up blood or blood clots, vomit blood or vomit looks like "coffee grounds", red or black stools that look like tar), skin changes (new wart, sore or reddish bump that bleeds or does not heal, change in size or color of a mole), hyperglycemia (increased thirst, urinating more often than normal or urinating an increased amount of urine), or severe diarrhea occur.