Dabrafenib

TAFINLAR is a kinase inhibitor indicated as a single agent for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. TAFINLAR is indicated, in combination with trametinib, for: the treatment of patients with unresectable or metastatic melanoma with BRAF V600E or V600K mutations as detected by an FDA-approved test. 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. the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with BRAF V600E mutation as detected by an FDA-approved test. the treatment of patients with locally advanced or metastatic anaplastic thyroid cancer (ATC) with BRAF V600E mutation, as detected by an FDA-approved test, and with no satisfactory locoregional treatment options. the treatment of adult and pediatric patients 1 year of age and older with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment and have no satisfactory alternative treatment options.

Dabrafenib is an inhibitor of some mutated forms of BRAF kinases with in vitro IC 50 values of 0.65, 0.5, and 1.84 nM for BRAF V600E, BRAF V600K, and BRAF V600D enzymes, respectively. Dabrafenib also inhibits wild-type BRAF and CRAF kinases with IC 50 values of 3.2 and 5.0 nM, respectively, and other kinases, such as SIK1, NEK11, and LIMK1 at higher concentrations. Some mutations in the BRAF gene, including those that result in BRAF V600E, can result in constitutively activated BRAF kinases that may stimulate tumor cell growth. Dabrafenib inhibits cell growth of various BRAF V600 mutation-positive tumors in vitro and in vivo. Dabrafenib and trametinib target two different kinases in the RAS/RAF/MEK/ERK pathway.

The recommended dosage of TAFINLAR in adult patients is 150 mg (two 75 mg capsules) orally twice daily. The recommended dosage for TAFINLAR in pediatric patients is based on body weight. Take TAFINLAR at least 1 hour before or 2 hours after a meal.

None. None.

New Primary Malignancies, Cutaneous and Non-Cutaneous: Can occur when TAFINLAR is administered as a single agent or with trametinib. Monitor patients for new malignancies prior to, or while on therapy, and following discontinuation of treatment. Tumor Promotion in BRAF Wild-type Tumors: Increased cell proliferation can occur with BRAF inhibitors. Hemorrhage: Major hemorrhagic events can occur in patients receiving TAFINLAR with trametinib. Monitor for signs and symptoms of bleeding. Cardiomyopathy: Assess left ventricular ejection fraction (LVEF) before treatment with TAFINLAR and trametinib, after one month of treatment, then every 2 to 3 months thereafter. Uveitis: Perform ophthalmological evaluation for any visual disturbances. Serious Febrile Reactions: Incidence and severity of pyrexia are increased with TAFINLAR and trametinib. Serious Skin Toxicities: Monitor for skin toxicities.

The following clinically significant adverse reactions are described elsewhere in the labeling: New Primary Malignancies Tumor Promotion in BRAF Wild-Type Tumors Hemorrhage Cardiomyopathy Uveitis Serious Febrile Reactions Serious Skin Toxicities Hyperglycemia Glucose-6-Phosphate Dehydrogenase Deficiency Hemophagocytic Lymphohistiocytosis There are additional adverse reactions associated with trametinib. Refer to the trametinib prescribing information for additional information. Most common adverse reactions (≥ 20%) for TAFINLAR as a single agent are hyperkeratosis, headache, pyrexia, arthralgia, papilloma, alopecia, and palmar-plantar erythrodysesthesia syndrome. Most common adverse reactions (≥ 20%) for TAFINLAR in combination with trametinib include: Unresectable or metastatic melanoma: pyrexia, rash, chills, headache, arthralgia, and cough.

Avoid concurrent administration of strong inhibitors of CYP3A4 or CYP2C8. Concomitant use with agents that are sensitive substrates of CYP3A4, CYP2C8, CYP2C9, CYP2C19, or CYP2B6 may result in loss of efficacy of these agents.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F). Store and dispense in the original bottle with the desiccant.