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Trametinib (Mekinist) Uses, Dosage, Side Effects

Trametinib

(tra-me′-ti-nib)

Mekinist

Classifications: ANTINEOPLASTIC; MITOGEN-ACTIVATED EXTRACELLULAR KINASE (MEK) INHIBITOR

Therapeutic: ANTINEOPLASTIC

Prototype: Erlotinib

Pregnancy Category: D

AVAILABILITY

Tablet

ACTION & THERAPEUTIC EFFECT

Trametinib is a reversible inhibitor of certain kinases that transmit signals and promote cellular proliferation and cancer growth. Trametinib inhibits BRAF V600 mutation-positive melanoma cell growth in vitro and in vivo.

USES

Treatment of unresectable or metastatic melanoma in patients with BRAF V600E or V600K mutations, as detected by an FDAapproved test.

CONTRAINDICATIONS

Symptomatic cardiomyopathy or LVEF decreases by 10% below pretreatment level and less than the LLN; drug related loss of vision or other visual disturbances; drug induced interstitial lung disease or pneumonitis; pregnancy (category D); lactation.

CAUTIOUS USE

Severe renal impairment; moderate or severe hepatic impairment; cardiac disorders;

CHF; respiratory disorders; ocular disorders; hypertension. Safety and efficacy in children not established.

ROUTE & DOSAGE

Malignant Melenoma

Adult: PO 2 mg once daily

Toxicity Dosage Adjustment

For specific toxicities see manufacturer guidelines.

ADMINISTRATION

Oral

Give at least 1 h before or 2 h after a meal.
Store at 2°–8° C (36°–46° F) and protect from moisture and light. Keep in original bottle and do not remove desiccant.

ADVERSE EFFECTS (≥1%)

CNS: Dizziness, dysgeusia. CV: Bradycardia, cardiomyopathy, hypertension. GI: Abdominal pain and tenderness, aphthous stomatitis, diarrhea, mouth ulceration, mucosal inflammation, and stomatitis. Hematological: Conjunctival hemorrhage, edema, epistaxis, gingival bleeding, hematochezia, hematuria, hemorrhoidal hemorrhage, lymphedema, melena, peripheral edema, rectal hemorrhage, and vaginal hemorrhage. Metabolic: Anemia, hypoalbuminemia, increased alkaline phosphatase, increased ALT/AST. Musculoskeletal: Rhabdomyolysis. Skin: Dermatitis acneiform, cellulitis, dry skin, folliculitis, paronychia, pruritus, rash. Special Senses: Dry eye, blurred vision.

Related for Nursing Implications and Drugs Guide Information

PHARMACOKINETICS

Absorption: 72% bioavailable. Peak: 1.5 h.

Distribution: 97.4% plasma protein bound. Metabolism: In liver.

Elimination: Fecal (80%) and renal (20%). Half-Life: 3.9–4.8 d.

NURSING IMPLICATIONS

Assessment & Drug Effects

Monitor cardiovascular status throughout therapy. Report promptly new-onset or worsening hypertension and S&S of heart failure.
Monitor pulmonary status throughout therapy. Report promptly signs of interstitial lung disease including cough, dyspnea, and signs of hypoxia or pleural effusion.
Monitor for and report promptly S&S of retinal detachment.
Evaluate for signs of skin toxicity. Report to prescriber development of progressive rash or signs of skin infection.
Monitor lab tests: Prior to therapy the presence of BRAF V600E or V600K mutation in tumor specimens must be confirmed.

Patient & Family Education

Report to prescriber if you experience any of the following S&S of heart failure or lung problems: Rapid heart rate, shortness of breath, unproductive cough, swelling of ankles and feet, excessive fatigue.
Report to prescriber if you experience blurred vision, see colored dots or halo around objects.
Report promptly signs of skin toxicity such as skin rash, acne, redness, swelling, peeling, or tenderness of hands or feet.
Women should use highly effective contraception during treatment due to potential for serious fetal harm.
Contact prescriber immediately if a pregnancy is suspected.

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