INDICATION AND IMPORTANT SAFETY INFORMATION

TAFINLAR^® (dabrafenib) capsules, in combination with MEKINIST^® (trametinib) tablets, is indicated for the adjuvant treatment of patients with melanoma with BRAF V600E or V600K mutations, as detected by an FDA-approved test, and involvement of lymph node(s), following complete resection.

Limitation of Use: TAFINLAR is not indicated for the treatment of patients with wild-type BRAF melanoma. MEKINIST is not indicated for the treatment of patients who have progressed on prior BRAF-inhibitor therapy.

IMPORTANT SAFETY INFORMATION

• New primary malignancies, cutaneous and noncutaneous, can occur. In the COMBI-d study in patients with unresectable or metastatic melanoma, the incidence of basal cell carcinoma in patients receiving TAFINLAR with MEKINIST was 3.3% compared with 6% of patients receiving single-agent TAFINLAR. Cutaneous squamous cell carcinoma (cuSCC), including keratoacanthoma, and new primary melanoma occurred in 3% and 0.5% of patients receiving TAFINLAR with MEKINIST, respectively. Noncutaneous malignancies occurred in 1.4% of patients who received the combination. Perform dermatologic evaluations prior to initiation of therapy, every 2 months while on therapy and for up to 6 months following discontinuation of TAFINLAR.
• TAFINLAR can cause paradoxical tumor growth in patients with BRAF wild-type melanoma. Confirm evidence of BRAF V600E or V600K mutation status prior to initiation of therapy.
• Hemorrhages, including major hemorrhages defined as symptomatic bleeding in a critical area or organ, can occur. No fatal hemorrhagic events were observed in the COMBI-AD study.
• Colitis and gastrointestinal perforation, sometimes fatal, can occur. Across clinical trials of MEKINIST, colitis occurred in 0.6% of patients and gastrointestinal perforation occurred in 0.3% of patients, respectively.
• In the COMBI-AD study, deep venous thrombosis (DVT) and pulmonary embolism (PE) occurred in 2% of patients receiving TAFINLAR with MEKINIST.
• Cardiomyopathy, including cardiac failure, can occur. In the COMBI-AD study, cardiomyopathy, defined as a decrease in left ventricular ejection fraction (LVEF) below the institutional lower limit of normal (LLN) with an absolute decrease in LVEF >10% below screening, occurred in 3% of patients receiving TAFINLAR with MEKINIST. Assess LVEF with an echocardiogram or a multigated acquisition (MUGA) scan before initiation of therapy, 1 month after initiation, then at 2- to 3-month intervals while on treatment.
• Ocular toxicities, including retinal vein occlusion (RVO), retinal pigment epithelial detachment (RPED), and uveitis can occur with TAFINLAR and MEKINIST. RVO may lead to macular edema, decreased visual function, neovascularization, and glaucoma.
• Interstitial lung disease or pneumonitis can occur in patients treated with TAFINLAR and MEKINIST. In the COMBI-AD study, <1% of patients treated with the combination developed pneumonitis.
• In patients treated with the combination in the metastatic melanoma studies, the incidence of fever was 54% and serious febrile reactions and fever of any severity complicated by severe rigors/chills, hypotension, dehydration, renal failure, or syncope occurred in 17%.
• Serious skin toxicity can occur. In the COMBI-d study, the overall incidence of any skin toxicity was 55% for patients receiving the combination. Across clinical trials of the combination, serious skin toxicity occurred in 0.7%.
• Hyperglycemia requiring an increase in the dose or initiation of insulin or oral hypoglycemic agent therapy can occur in patients treated with TAFINLAR and MEKINIST. Monitor serum glucose levels upon initiation, and as clinically appropriate in patients with preexisting diabetes or hyperglycemia.
• Closely monitor patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency, as TAFINLAR confers a potential risk of hemolytic anemia in these patients.
• TAFINLAR and MEKINIST can cause fetal harm when administered to a pregnant woman.
• In the COMBI-AD study, the most common adverse reactions (≥20%) for the combination were pyrexia (63%), fatigue (59%), nausea (40%), headache (39%), rash (37%), chills (37%), diarrhea (33%), vomiting (28%), arthralgia (28%), and myalgia (20%). The most common grade 3 or 4 adverse reactions (>2%) for the combination were pyrexia (5%) and fatigue (5%).
• In the COMBI-AD study, other clinically important adverse reactions observed in <20% of patients receiving the combination were blurred vision (6%), decreased ejection fraction (5%), and rhabdomyolysis (<1%).
• In the COMBI-AD study, treatment-emergent laboratory abnormalities occurring in ≥20% of patients receiving the combination were hyperglycemia (63%), increased alanine aminotransferase (AST) (57%), increased alanine aminotransferase (ALT) (48%), neutropenia (47%), hypophosphatemia (42%), increased blood alkaline phosphatase (38%), lymphopenia (26%), anemia (25%), and hypoalbuminemia (25%).

Please click here for full Prescribing Information for TAFINLAR and click here for full Prescribing Information for MEKINIST.