Important Safety Information

New Primary Malignancies, Cutaneous and Noncutaneous. Perform dermatologic evaluations prior to initiation of therapy, every 2 months while on therapy, and for up to 6 months following...

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INDICATIONS

TAFINLAR® (dabrafenib) capsules, in combination with MEKINIST® (trametinib) tablets, is indicated:

  • for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test
  • 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
  • for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test
  • for the treatment of patients with locally advanced or metastatic anaplastic thyroid cancer (ATC) with BRAF V600E mutation and with no satisfactory locoregional treatment options

Limitations of Use: TAFINLAR is not indicated for the treatment of patients with wild-type BRAF melanoma, NSCLC, or ATC.

 

IMPORTANT SAFETY INFORMATION

New Primary Malignancies, Cutaneous and Noncutaneous. Perform dermatologic evaluations prior to initiation of therapy, every 2 months while on therapy, and for up to 6 months following discontinuation of the combination.

Monitor patients closely for signs or symptoms of noncutaneous malignancies. Permanently discontinue TAFINLAR for monomeric G protein (RAS)-mutation–positive noncutaneous malignancies.

Tumor Promotion in BRAF Wild-type Tumors. Increased cell proliferation can occur with BRAF inhibitors. Confirm evidence of BRAF V600E or V600K mutation status prior to initiation of therapy.

Hemorrhage. Hemorrhage, including major hemorrhage, defined as symptomatic bleeding in a critical area or organ, can occur with the combination. Fatal cases have been reported.

Permanently discontinue TAFINLAR for all grade 4 hemorrhagic events and for any grade 3 hemorrhagic events that do not improve. Withhold TAFINLAR for grade 3 hemorrhagic events; if improved, resume at the next lower dose level. Permanently discontinue MEKINIST for all grade 4 hemorrhagic events and for any grade 3 hemorrhagic events that do not improve. Withhold MEKINIST for grade 3 hemorrhagic events; if improved, resume at the next lower dose level.

Colitis and Gastrointestinal Perforation. Colitis and gastrointestinal perforation, including fatal outcomes, have been reported in patients receiving MEKINIST. Monitor patients closely for colitis and gastrointestinal perforations.

Venous Thromboembolic Events. Advise patients to seek medical care immediately if they develop symptoms of deep venous thrombosis (DVT) or pulmonary embolism (PE), such as shortness of breath, chest pain, or arm or leg swelling. Permanently discontinue TAFINLAR and MEKINIST for life-threatening PE. Withhold MEKINIST for uncomplicated DVT and PE for up to 3 weeks; if improved, MEKINIST may be resumed at a lower dose.

Cardiomyopathy. Cardiomyopathy, including cardiac failure, can occur. Assess left ventricular ejection fraction before treatment with TAFINLAR and MEKINIST, after 1 month of treatment, then every 2 to 3 months thereafter.

Ocular Toxicities.
Retinal vein occlusion (RVO) may lead to macular edema, decreased visual function, neovascularization, and glaucoma. Urgently (within 24 hours) perform ophthalmologic evaluation for a patient-reported loss of vision or other visual disturbances. Permanently discontinue MEKINIST in patients with documented RVO.

Retinal pigment epithelial detachment (RPED) can occur with MEKINIST administration. Withhold MEKINIST if RPED is diagnosed. If resolution of the RPED is documented on repeat ophthalmologic evaluation within 3 weeks, resume MEKINIST at same or reduced dose. Reduce the dose or discontinue MEKINIST if no improvement after 3 weeks.

Uveitis (including iritis and iridocyclitis) can occur with TAFINLAR. Perform ophthalmologic evaluation for any visual disturbances. Monitor patients for visual signs and symptoms of uveitis (eg, change in vision, photophobia, and eye pain). Permanently discontinue TAFINLAR for persistent grade 2 or greater uveitis of >6 weeks.

Interstitial Lung Disease (ILD)/Pneumonitis. Withhold MEKINIST in patients presenting with new or progressive pulmonary symptoms and findings including cough, dyspnea, hypoxia, pleural effusion, or infiltrates, pending clinical investigations. Permanently discontinue MEKINIST for patients diagnosed with treatment-related ILD or pneumonitis.

Serious Febrile Reactions. Serious febrile reactions or fever of any severity complicated by hypotension, rigors or chills, dehydration, or renal failure can occur with TAFINLAR and MEKINIST. The incidence and severity of pyrexia increase when TAFINLAR is administered with MEKINIST. Withhold TAFINLAR for temperature of ≥101.3ºF or fever complicated by hypotension, rigors or chills, dehydration, or renal failure, and evaluate for signs and symptoms of infection. Withhold MEKINIST for a temperature of ˃104ºF or fever complicated by hypotension, rigors or chills, dehydration, or renal failure, and evaluate for signs and symptoms of infection. Monitor serum creatinine and other evidence of renal function during and following severe pyrexia. Upon resolution, resume at same or lower dose. Administer antipyretics as secondary prophylaxis when resuming TAFINLAR and/or MEKINIST if the patient had a prior episode of severe febrile reaction or fever associated with complications. Administer corticosteroids (eg, prednisone 10 mg daily) for at least 5 days for second or subsequent pyrexia if temperature does not return to baseline within 3 days of onset of pyrexia, or for pyrexia associated with complications such as hypotension, severe rigors or chills, dehydration, or renal failure, and there is no evidence of active infection.

Serious Skin Toxicities. Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported during treatment with the combination. Monitor for new or worsening serious skin reactions. Permanently discontinue the combination for SCARs. For other skin toxicities, withhold TAFINLAR and/or MEKINIST for intolerable or severe skin toxicity. Resume TAFINLAR and/or MEKINIST at a lower dose in patients with improvement or recovery from skin toxicity within 3 weeks. Permanently discontinue TAFINLAR and/or MEKINIST if skin toxicity has not improved within 3 weeks.

Hyperglycemia. Monitor serum glucose levels upon initiation, and as clinically appropriate in patients with preexisting diabetes or hyperglycemia. Initiate or optimize antihyperglycemic medications as clinically indicated.

Glucose-6-Phosphate Dehydrogenase Deficiency. Closely monitor for hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency.

Embryo-fetal Toxicity. TAFINLAR and MEKINIST can cause fetal harm.

Most Common Adverse Reactions. Most common adverse reactions (≥20%) for TAFINLAR with MEKINIST include:

  • Metastatic melanoma: pyrexia, nausea, rash, chills, diarrhea, headache, vomiting, hypertension, arthralgia, peripheral edema, and cough
  • Adjuvant melanoma: pyrexia, fatigue, nausea, headache, rash, chills, diarrhea, vomiting, arthralgia, and myalgia
  • NSCLC: pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea

Please see full Prescribing Information for TAFINLAR and full Prescribing Information for MEKINIST.