Adult Dosing

After confirmation of the presence of BRAF V600E or V600K mutation in tumor specimens

• 2 mg PO once daily taken at least 1 hour before or at least 2 hours after a meal as a single agent regimen
• 2 mg PO once daily in combination with dabrafenib 150 mg PO bid

Note:

• Refer to Full prescribing information prior to prescribing for uses and dosing including toxicity-related dose adjustments

Pediatric Dosing

• Safety and effectiveness in pediatric patients have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Indicated as a single agent or in combination with dabrafenib for unresectable or metastatic melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test

• Hypersensitivity to any of the ingredients of the product

• N/A

Renal Dose Adjustment

• Mild renal impairment: No dose adjustments
• Moderate-severe renal impairment: Dose adjustments not defined

Hepatic Dose Adjustment

• Mild hepatic impairment: No dose adjustments
• Moderate-severe hepatic impairment: Dose adjustments not defined

• Cardiomyopathy has been associated with patients treated with trametinib. Closely moniotor left ventricular ejection fraction (LVEF) by echocardiogram or before initiation of therapy one month and then at 2 to 3 month intervals while on treatment. Withhold treatment if absolute LVEF value decreases by 10% from pre-treatment values and is less than the lower limit of normal
• Permanently discontinue therapy in patients with symptomatic cardiomyopathy or persistent, asymptomatic LVEF dysfunction that does not resolve within 4 weeks
• Retinal pigment epithelial detachments (RPED) can occur during treatment. Perform ophthalmological evaluation at any time a patient reports visual disturbances.
• Discontinue therapy if RPED is diagnosed. If resolution of RPED is documented on repeat ophthalmological evaluation within 3 weeks, resume therapy at a reduced dose
• Urgently perform ophthalmological evaluation for patient-reported loss of vision or other visual disturbances. Permanently discontinue therapy in patients with documented retinal vein occlusion
• Therapy has been associated with reports of interstitial lung disease (ILD) or pneumonitis.
• Abruptly discontinue therapy in patients presenting with new or progressive pulmonary symptoms and findings including cough, dyspnea, hypoxia, pleural effusion, or infiltrates, pending clinical investigations
• Skin toxicity including rash, dermatitis, acneiform rash, palmar-plantar erythrodysesthesia syndrome, and erythema has been associated with therapy. Closely monitor patients for skin toxicities and for secondary infections
• Therapy may cause fetal harm when administered to a pregnant woman. 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 hazard to a fetus
• New primary malignancies, cutaneous and non-cutaneous, can occur when trametinib is used in combination with dabrafenib. Monitor for new malignancies prior to initiation of therapy while on therapy, and following discontinuation of the combination treatment
• Major hemorrhages can occur when used in combination with dabrafenib, hence observe for signs and symptoms of bleeding
• Deep vein thrombosis and pulmonary embolismcan occur when used in combination with dabrafenib
• Serious febrile reactions can occur when trametinib is used in combination with dabrafenib

Pregnancy Category:D

Breastfeeding: Safety unknown. As many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

• DERM: Rash, dermatitis acneiform, dry skin, pruritus, paronychia
• GI: Diarrhea, stomatitis, abdominal pain
• CV: Hypertension
• HEMA: Lymphedema, hemorrhage

• Protein Kinase Inhibitors; reversible inhibitor of mitogen-activated extracellular signal regulated kinase 1 256 (MEK1) and MEK2 activation and of MEK1 and MEK2 kinase activity; inhibits BRAF V600 mutation-positive 260 melanoma cell growth in vitro and in vivo
• Bioavailability: 72% (2 mg)
• Metabolized predominantly via deacetylation alone or with mono­oxygenation or in combination with glucuronidation biotransformation pathways
• Excretion: Feces (> 80%); urine (< 20%)
• Half-life: 3.9-4.8 days

US Trade Name(s)

• Mekinist

US Availability

Mekinist

• TABS: 0.5, 1, 2 mg

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• N/A

UK Availability

• N/A

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Hematology/Oncology

Antineoplastics

Tyrosine Kinase Inhibitors