trametinib

(redirected from Mekinist)

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.
Drug Guide, © 2015 Farlex and Partners
References in periodicals archive ?
*Oncology grew 10% (cc) driven by continued growth from Promacta/Revolade, Tafinlar + Mekinist and Jakavi, uptake of Kisqali and Kymriah and contribution from the AAA acquisition
Currently, three MEK inhibitors have been approved and marketed globally: Novartis's MEKINIST (trametinib), Roche's COTELLIC (cobimetinib) and Array's Mektovi (binimetinib).
Tawbi and his colleagues said that, while cross-trial comparisons have inherent limitations, the rate of intracranial response seen in this trial is similar to what was seen in the COMBI-MB study of dabrafenib (Tafinlar) plus trametinib (Mekinist) in patients with BRAF-mutant melanoma and brain metastases.
Novartis announced results from the COMBI-d and COMBI-v clinical trials, concluding that first-line treatment with Tafinlar and Mekinist "offers both overall and progression-free long-term survival benefits to patients with unresectable or metastatic BRAF-mutation positive melanoma." Researchers reported that 34% of all patients in the pooled analysis who were treated with Tafinlar plus Mekinist survived at five years, the company said in a statement.
Promacta/Revolade sales were $295 million and Tafinlar + Mekinist sales were $291 million, both up 30%.
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.
The updated edition contains information on the latest immunotherapy and genetically targeted treatments, including ipilimumab (Yervoy), pembrolizumab (Keytruda), nivolumab (Opdivo), vemurafenib (Zelboraf), dabrafenib (Tafinlar), and trametinib (Mekinist).
This has led to the approval of several new drug agents indicated for CM since 2011, namely Sylatron (peginterferon alfa-2b), Yervoy (ipilimumab), Opdivo, (nivolumab), Keytruda (pembrolizumab), Zelboraf (vemurafenib), Tafinlar (dabrafenib) and Mekinist (trametinib).
The seven new antineoplastic agents are adotrastuzumab emtansine (Kadcyla) for HER2-positive breast cancer; afatinib (Gilotrif) for non-small cell lung cancer; dabrafenib (Tafinlar) for unresectable or metastatic melanoma; ibrutinib (Imbruvica) for mantle cell lymphoma or chronic lymphocytic leukemia; obinutuzumab (Gazyva) for chronic lymphocytic leukemia; pomalidomide (Pomalyst) for multiple myeloma; and trametinib (Mekinist) for unresectable or metastatic melanoma.
Within the Journal North 40 Index, GLAXOSMITHKLINE announced that it had completed Phase 3 trials in investigating the combination of Tafinlar and Mekinist in patients with melanoma.