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Trametinib

Class
Targeted therapy
Subclass
MEK inhibitors
Generic name
Trametinib
Brand names
Mekinist®
Common formulations
Film-coated tablet
Dosage and administration
Adults patients
Treatment of anaplastic thyroid cancer in patients with BRAF V600E mutation • Locally advanced or metastatic
•
2 mg PO daily until disease recurrence or unacceptable toxicity
Administered in combination with dabrafenib.
Indications for use
Labeled indications
Adults
•
Treatment of anaplastic thyroid cancer in patients with BRAF V600E mutation (locally advanced or metastatic)
•
Treatment of non-small cell lung cancer in patients with ALK rearrangement (metastatic)
•
Treatment of thyroid cancer
Safety risks
Boxed warnings
Malignancies
•
Use extreme caution with BRAF V600 mutation-positive, unresectable or metastatic melanoma who received trametinib in combination with dabrafenib. Regularly monitor patients for the development of new primary malignancies during Trametinib treatment. Evaluate and manage the new primary malignancy according to standard medical practices. Seek immediate medical attention for proper diagnosis and treatment.
Contraindications
A known hypersensitivity to drug
•
Monitor patients for new or worsening skin reactions and secondary infections
Warnings and precautions
Bleeding
•
Use extreme caution with risk factors for Bleeding events (e.g., intracranial bleeding and GI bleeding). Monitor patients who receive trametinib for signs or symptoms of bleeding. Interruption of therapy, a dose reduction, or permanent therapy discontinuation may be necessary in patients who develop grade 3 or 4 bleeding.
Cardiomyopathy, LV dysfunction
•
Use extreme caution with BRAF V600 mutation-positive, unresectable or metastatic melanoma who received trametinib as monotherapy or in combination with dabrafenib. Evaluate cardiac function prior to starting trametinib (e.g., echocardiogram). Interruption of therapy, a dose reduction, and/or permanent discontinuation may be necessary in patients who develop LV dysfunction.
DVT, PE
•
Use extreme caution with a history of venous thromboembolic disease. Implement appropriate thromboprophylaxis measures and closely monitor patients for signs of DVT and PE during Trametinib treatment. Initiate prompt medical intervention, including anticoagulant therapy, for the management of DVT or PE. Seek immediate medical attention.
Gastrointestinal perforation, colitis
•
Use caution with inflammation of the colon. Monitor patients for symptoms of colitis and promptly manage any gastrointestinal adverse effects during Trametinib treatment. Discontinue Trametinib and provide appropriate medical intervention, which may include corticosteroids or surgical intervention.
Hyperglycemia
•
Use caution with a history of diabetes mellitus. Monitor serum glucose levels at baseline and as clinically indicated during therapy. Initiate or optimize anti-hyperglycemic agents in these patients as necessary.
ILD, pneumonitis
•
Use extreme caution with a history of pulmonary illness. Monitor patients regularly for signs and symptoms of ILD and pneumonitis during Trametinib treatment. Discontinue Trametinib and initiate appropriate medical intervention, which may include systemic corticosteroids, to manage ILD and pneumonitis.
Retinal detachment, central retinal vein occlusion
•
Use caution with a history of vision problems. Ophthalmological exams should be performed periodically and promptly in patients who report vision problems. Interruption of therapy, a dose reduction, or permanent therapy discontinuation may be necessary for patients who develop retinal detachments and retinal vein occlusion.
Specific populations
Renal impairment
eGFR 20-50 mL/min/1.73 m²
•
Use acceptable. No dose adjustment required. Monitor for rhabdomyolysis, acute renal failure, skin toxicities and hypercalcemia.
eGFR 10-20 mL/min/1.73 m²
•
Use with caution. Monitor for rhabdomyolysis, acute renal failure, skin toxicities and hypercalcemia.
eGFR < 10 mL/min/1.73 m²
•
Use with caution. Monitor for rhabdomyolysis, acute renal failure, skin toxicities and hypercalcemia.
Renal replacement therapy
Continuous renal replacement
•
Use with caution. Dose as in eGFR 10-20 mL/min/1.73 m². Monitor for rhabdomyolysis, acute kidney injury, dermatological effects and hypercalcemia.
Intermittent hemodialysis
•
Use with caution. Dose as in eGFR < 10 mL/min/1.73 m². Monitor for rhabdomyolysis, acute kidney injury, dermatological effects and hypercalcemia.
Peritoneal dialysis
•
Use with caution. Dose as in eGFR < 10 mL/min/1.73 m². Monitor for rhabdomyolysis, acute kidney injury, dermatological effects and hypercalcemia.
Hepatic impairment
Child-Pugh A (mild)
•
Use acceptable. No dose adjustment required.
Child-Pugh B (moderate)
•
No guidance available. - Consider the risks versus benefits of treatment.
Child-Pugh C (severe)
•
No guidance available. - Consider the risks versus benefits of treatment.
Pregnancy and breastfeeding
Pregnancy
All trimesters • Australia Category: D
•
Avoid use. Evidence of fetal harm in humans. Adequate methods of contraception should be encouraged during therapy and for 4 months following discontinuation of therapy.
•
If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus.
Breastfeeding
Do not use during breastfeeding.
Unknown amount excreted in breastmilk.
Unknown drug levels in breastfed infants.
Adverse reactions
Very common > 10%
•
AV block, acneiform lesions, dry skin patches, edema, hypertension, paronychia, peripheral edema, abdominal pain, arthralgia, constipation, cough, diarrhea, dizziness, fatigue, fever, headache, loss of appetite, myalgia, nausea, nosebleed, skin rash, throat pain, vomiting, weight gain, shivering
Common 1-10%
•
Basal cell carcinoma, bradycardia, cardiomyopathy, colitis, cutaneous squamous cell carcinoma, gastrointestinal bleeding, LBBB, RBBB, photosensitivity of skin, retinal detachment, rhabdomyolysis, sarcoidosis, sepsis, stomatitis, venous thromboembolism
Uncommon < 1%
•
Branch retinal vein occlusion, cerebral hemorrhage, gastrointestinal perforation, melanoma
Unknown frequency
•
Carcinomatosis, DRESS syndrome, ↓ LVEF, dermatitis, hemophagocytic lymphohistiocytosis, interstitial lung disease, ↑ blood glucose, ↑ liver enzymes, pulmonary embolism, pneumonia, pneumonitis, abnormal uterine bleeding, dyspnea, respiratory distress, Stevens-Johnson syndrome, tubulointerstitial nephritis, upper respiratory tract infections, uveitis
Interactions
Drug(s)
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