Dabrafenib
TAFINLAR
What it isBRAF V600 kinase inhibitor; BRAF-mutant melanoma, lung and thyroid cancer.
Why this oneRapid tumor response, and combining it with trametinib delays resistance.
What limits itIt paradoxically activates the pathway in BRAF-wild-type cells, causing squamous skin lesions. Pyrexia; CYP3A4-dependent.
FDA-approved for
- BRAF V600 melanoma (2013)
- NSCLC, anaplastic thyroid cancer
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| BRAF V600E/V600K melanoma (single agent for V600E, or with trametinib); unresectable/metastatic and adjuvant | Adults | 150 mg BID | 150 mg BID | |
| BRAF V600E NSCLC, anaplastic thyroid cancer, or other solid tumors (with trametinib) | Adults | 150 mg BID | 150 mg BID | |
| BRAF V600E solid tumors / low-grade glioma (with trametinib) | Pediatrics ≥1 yr (capsules ≥26 kg; oral suspension ≥8 kg) | Weight-based BID (capsules: 26–37 kg 75 mg, 38–50 kg 100 mg, ≥51 kg 150 mg) |
Renal Undefined
Hepatic Mild: no dose adjustment. Moderate–severe: increased exposure possible; no dosage established
Instructions
- Take on an empty stomach (≥1 h before or 2 h after a meal)
- Capsules: swallow whole; do not open, crush, or break
- Take ~12 h apart at the same time each day
- Do not take a missed dose within 6 h of the next; if vomiting occurs, do not take an extra dose
- Oral suspension: do not swallow whole/chew/crush; disperse in water and give within 30 min
Cautions
- New primary malignancies (cutaneous & non-cutaneous)
- Tumor promotion in BRAF wild-type tumors — confirm V600 mutation first
- Hemorrhage (with trametinib)
- Cardiomyopathy — monitor LVEF
- Uveitis
- Serious febrile reactions (pyrexia)
- Serious skin toxicities (SJS, DRESS)
- Hyperglycemia
- Hemolytic anemia in G6PD deficiency
- Hemophagocytic lymphohistiocytosis
- Embryo-fetal toxicity — use non-hormonal contraception
Adverse reactions
- Hyperkeratosis
- Headache
- Pyrexia
- Arthralgia
- Papilloma
- Alopecia
- Palmar-plantar erythrodysesthesia syndrome
Pregnancy Can cause fetal harm; verify pregnancy status and use effective non-hormonal contraception
Lactation Do not breastfeed during treatment and for 2 weeks after last dose
NO BOXED WARNINGS
Principal riskParadoxical squamous skin lesions; pyrexia
Cost, est. cash$5,000–$30,000+/month or cycle
Generic entry2038 est.
Classes and tags
Clinical profile
Legacy pregnancy categoryD
Defining liabilityMyelosuppression and agent-specific hepatic, cardiac, pulmonary, neurologic or reproductive toxicity require oncology monitoring.
Mechanism of action: Dabrafenib ballicule
