trametinib

trametinib

Mekinist

Indications

Action

Pharmacokinetics

Time/action profile (response)

Contraindications/Precautions

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

Route/Dosage

Availability

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

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.