Tafinlar
Unresectable or metastatic melanoma with BRAF V600E mutation (with trametinib); Adjuvant treatment of melanoma with BRAF V600E/K mutations following complete resection (with trametinib); Metastatic NSCLC with BRAF V600E mutation (with trametinib); Locally advanced or metastatic anaplastic thyroid cancer with BRAF V600E mutation (with trametinib); Solid tumors with BRAF V600E mutation following prior treatment with no satisfactory alternatives (with trametinib, adults); Low-grade glioma with BRAF V600E mutation (with trametinib, pediatric ≥1 year).
150 mg orally twice daily (with trametinib 2 mg once daily)
Take on empty stomach: at least 1 hour before or 2 hours after a meal
Take doses approximately 12 hours apart
Dose reductions: 100 mg BID, then 75 mg BID, then 50 mg BID
Capsules: 50 mg, 75 mg
None listed.
- New Primary Malignancies: Cutaneous squamous cell carcinoma (SCC) in 7% (vs 2% with trametinib combo). Non-cutaneous malignancies including RAS-mutant malignancies. Monitor with skin exams monthly.
- Hemorrhage: Including fatal intracranial hemorrhage. Permanently D/C for Grade 4.
- Venous Thromboembolism: DVT/PE in 6%.
- Cardiomyopathy: Decreased LVEF in 9% (with trametinib). Monitor LVEF at baseline, 1 month, then every 2-3 months.
- Pyrexia: In 57% (with trametinib). Serious febrile reactions including hypotension and rigors. Interrupt for temperature ≥38.5°C.
- Uveitis/Iritis: In 1%. Monitor for visual symptoms.
- Hyperglycemia: In 7%.
Pyrexia (57%), fatigue (38%), nausea (35%), headache (30%), rash (24%), chills (24%), arthralgia (22%), diarrhea (20%), vomiting (18%), hypertension (14%), cough (12%), myalgia (11%)
Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.
Dabrafenib is an inhibitor of BRAF serine/threonine kinase. BRAF V600E mutations result in constitutive activation of the RAS/RAF/MEK/ERK pathway. Dabrafenib inhibits BRAF V600E, V600K, and V600D kinases, blocking downstream MEK and ERK phosphorylation and reducing cell proliferation. It is typically used in combination with the MEK inhibitor trametinib to improve efficacy and delay resistance compared to BRAF inhibitor monotherapy.
Tmax: 2 hours. Half-life: 8 hours (active metabolites: hydroxy-dabrafenib 10h, desmethyl-dabrafenib 21-22h). Protein binding: 99.7%. Metabolized by CYP2C8 and CYP3A4. Excreted in feces (72%) and urine (23%). High-fat meals reduce AUC by 31%.
Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.
- COMBI-d — Dabrafenib + trametinib vs. dabrafenib + placebo in BRAF V600E/K metastatic melanoma. Phase III, n=423.
- COMBI-v — Dabrafenib + trametinib vs. vemurafenib in BRAF V600 metastatic melanoma. Phase III, n=704.