trametinib

trametinib

(tra-me-ti-nib) ,

Mekinist

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: kinase inhibitors
Pregnancy Category: D

Indications

Treatment of metastatic/unresectable melanoma with the BRAF V660E or V600K mutation.

Action

Inhibits the activity of kinases, enzymes that promote cellular proliferation

Therapeutic effects

Decreased progression of melanoma.

Pharmacokinetics

Absorption: Well absorbed following oral administration
Distribution: Unk
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:

Time/action profile (response)

ROUTEONSETPEAKDURATION
PO1 mo2 mo5–7mos

Contraindications/Precautions

Contraindicated in: Obstetric: May cause fetal harm Lactation: Breastfeeding should be avoided
Use Cautiously in: Obstetric: Patients with child-bearing potential Pediatric: Safe and effective use in children has not been established

Adverse Reactions/Side Effects

Central nervous system

  • dizziness

Ear, Eye, Nose, Throat

  • blurred vision
  • dry eyes
  • retinal pigment epithelial detachment
  • retinal vein occlusion

Respiratory

  • interstitial lung disease/pneumonitis (life-threatening)

Cardiovascular

  • cardiomyopathy (life-threatening)
  • hypertension (most frequent)

Gastrointestinal

  • abdominal pain (most frequent)
  • diarrhea (most frequent)
  • ↑ liver enzymes (most frequent)
  • stomatitis (most frequent)
  • dysgeusia

Dermatologic

  • acneiform dermatitis (most frequent)
  • rash (most frequent)
  • skin toxicity (most frequent)
  • cellulitis
  • dry skin
  • folliculitis
  • palmar-plantar erythrodysesthesia syndrome
  • paranychia
  • pruritus

Hematologic

  • bleeding (most frequent)

Musculoskeletal

  • rhabdomyolysis

Miscellaneous

  • lymphedema (most frequent)

Interactions

Drug-Drug interaction

None noted

Route/Dosage

Oral (Adults) 2 mg daily continued until disease progression or unacceptable toxicity; dose modifications recommended for various levels of toxicity.

Availability

Tablets: 0.5 mg, 1 mg, 2 mg

Nursing implications

Nursing assessment

  • Assess left ventricular ejection fraction (LVEF) by echocardiogram or multigated acquisition (MUGA) scan before starting, after 1 month, and at 2–3 month 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.
  • Perform ophthalmalogic evaluation at baseline; compare if patient reports visual disturbance. If Grade 2–3 retinal pigment epithelial detachment (RPED) occurs, withhold trametinib for up to 3 wks. If Grade 2–3 RPED improves to Grade 0–1 within 3 wks, resume trametinib at a lower dose (0.5 mg) or discontinue in patients taking 1 mg daily. If retinal vein occlusion occurs or if Grade 2–3 RPED does not improve to at least Grade 1 within 3 wks, 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 skin toxicities and secondary infections during therapy. If Grade 2 rash occurs, reduce dose by 0.5 mg or discontinue in patients taking 1 mg daily. If intolerable Grade 2 rash that does not improve within 3 wks following dose reduction or if Grade 3 or 4 rash occurs, withhold trametinib for up to 3 wks. If improved within 3 wks, resume trametinib at a lower dose (0.5 mg) or discontinue in patients taking 1 mg daily. If intolerable Grade 2 or Grade 3 or 4 rash that does not improve despite interruption of therapy for 3 wks, permanently discontinue trametinib.
  • Monitor blood pressure periodically during therapy. May cause hypertension.
  • Lab Test Considerations: May cause ↑ AST, ALT, and alkaline phosphatase.
    • May cause hypoalbumemia.
    • May cause anemia.

Potential Nursing Diagnoses

Impaired skin integrity (Indications)

Implementation

  • Evidence of BRAF V600E or V600K mutations must be confirmed prior to starting therapy with trametinib.
  • Oral: Administer twice daily about 12 hrs apart. Administer on an empty stomach at least 1 hr before or 2 hrs after a meal. Swallow tablets whole; do not break, crush, break, or chew.

Patient/Family Teaching

  • Instruct patient to take trametinib as directed at least 1 hr before or 2 hrs after meals. Take missed doses as soon as remembered unless within 12 hrs of next dose, then skip missed dose and take regularly scheduled dose.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
  • 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) or severe diarrhea occur.
  • Advise female patient to use a highly effective form of contraception during and for at least 4 months after treatment. Use a non-hormonal form of contraception; trametinib may decrease effectiveness of hormonal contraceptives. Advise patient to notify health care professional if pregnancy is suspected and to avoid breastfeeding. May impair fertility in females.

Evaluation/Desired Outcomes

  • Decrease in progression of malignant melanoma.
References in periodicals archive ?
So rather than going down the chemotherapy route, he was put on a dose of two sets of tablets, dabrafenib and trametinib, daily.
Two targeted therapies are now approved by the US Food and Drug Administration for treating thyroid cancer patients: a combination of dabrafenib plus trametinib for BRAF V600E-mutated anaplastic thyroid cancer; and larotrectinib for solid tumors harboring a NTRK gene fusion, regardless of cancer type.
A GIANT CONGENITAL MELANOCYTIC NEVUS (GCMN) in a 7-year-old girl was effectively treated with the MEK inhibitor trametinib, according to a case report published in Pediatrics.
(1) These include epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) (gefitinib, erlotinib, and afatinib) for EGFR mutations, combined dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) for BRAF p.V600E mutation, and ALK tyrosine kinase inhibitors (crizotinib, ceritinib, and alectinib) for ALK translocations.
BRAF inhibitor dabrafenib with MEK inhibitor trametinib (ClinicalTrials.gov: NCT02124772).
Currently, three MEK inhibitors have been approved and marketed globally: Novartis's MEKINIST (trametinib), Roche's COTELLIC (cobimetinib) and Array's Mektovi (binimetinib).
Drug company Novartis said the combination of dabrafenib and trametinib has been recommended as a treatment option for the treatment of adult patients with stage III melanoma with a BRAF V600 mutation, following surgery.
Tafinlar (dabrafenib) and Mekinist (trametinib) combined have been approved to treat anaplastic thyroid cancer caused by an abnormal BRAF V600E gene, the agency said Friday in a news release.
Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: a multicentre, double-blind, phase 3 randomised controlled trial.
Current systemic therapies for metastatic MM according to the ESMO guidelines [7] and their most recent updates include anti-PD-1 antibodies (nivolumab, pembrolizumab) or anti-CTLA4 inhibitors (ipilimumab) if BRAF is wild-type, or BRAF+MEK inhibitors (vemurafenib, encorafenib, dabrafenib with or without binimetinib, cobimetinib, trametinib) as an additional option for BRAF mutated variants.