• Metastatic or unresectable melanoma in patients with the BRAF V600E mutation (as monotherapy).
• Metastatic or unresectable melanoma in patients with the BRAF V600E or V600K mutation (in combination with trametinib).
• Adjuvant treatment of melanoma in patients with the BRAF V600E or V600K mutation and lymph node involvement following complete resection (in combination with trametinib).
• Metastatic non-small cell lung cancer (NSCLC) in patients with the BRAF V600E mutation (in combination with trametinib).
• Locally advanced or metastatic anaplastic thyroid cancer in patients with the BRAF V600E mutation and no satisfactory locoregional treatment options (in combination with trametinib).
• Unresectable or metastatic solid tumors with the BRAF V600E mutation in patients who have progressed following prior treatment and have no satisfactory alternative treatment options (in combination with trametinib).
• Low-grade glioma with a BRAF V600E mutation in patients who require systemic therapy (in combination with trametinib).

Contraindicated in:

• BRAF wild-type solid tumors (may ↑ proliferation)
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• History of glucose-6-phosphate dehydrogenase (G6PD) deficiency (may cause hemolytic anemia)
• Diabetes
• Moderate or severe hepatic impairment
• Moderate or severe renal impairment
• Rep: Women of reproductive potential and men with female partners of reproductive potential
• Pedi: Safety and effectiveness not established in children <18 yr (as monotherapy) or <1 yr (in combination with trametinib for unresectable or metastatic solid tumors or low-grade gliomas with BRAF V600E mutation).

CV: HF, THROMBOEMBOLISM.

Derm: alopecia, hyperkeratosis, palmar-plantar erythrodysesthesia, papilloma, cutaneous squamous cell carcinoma, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), photosensitivity, STEVENS-JOHNSON SYNDROME.

EENT: iritis, retinal detachment, uveitis.

Endo: hyperglycemia.

F and E: hypophosphatemia, hyponatremia.

GI: constipation, PANCREATITIS.

Hemat: bleeding, hemophagocytic lymphohistiocytosis.

MS: arthralgia, back pain, myalgia.

Neuro: headache, fatigue, peripheral neuropathy.

Resp: cough, nasopharyngitis.

Misc: fever (including serious febrile reactions), chills, MALIGNANCY.

Drug-Drug:

• Concurrent use of strong CYP3A4 inhibitors or strong CYP2C8 inhibitors, including ketoconazole, nefazodone, clarithromycin, and gemfibrozil, may ↑ levels and ↑ the risk of toxicity and should be avoided.
• Concurrent use of strong CYP3A4 inducers or strong CYP2C8 inducers, including carbamazepine, phenobarbital, phenytoin, and rifampin, may ↓ levels and ↓ effectiveness.
• Drugs that ↑ gastric pH, including antacids, H₂-receptor antagonists, and proton pump inhibitors, may ↓ levels and effectiveness.
• May ↓ effectiveness of other CYP3A4 substrates and CYP2C9 substrates, including midazolam, warfarin, dexamethasone, and hormonal contraceptives.

Drug-Natural Products:

• St. John's wort↓ levels and may ↓ effectiveness; concurrent use should be avoided.

• Capsules: 50 mg; 75 mg;
• Tablets for oral suspension: 10 mg;

Treatment of Unresectable/Metastatic Melanoma, Metastatic Non-Small Cell Lung Cancer, or Locally Advanced/Metastatic Anaplastic Thyroid Cancer

• PO (Adults): 150 mg twice daily until disease progression or unacceptable toxicity.
Tablets for Oral Suspension
• PO (Adults 51 kg): 150 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults 46–50 kg): 130 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults 42–45 kg): 110 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults 38–41 kg): 100 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults 34–37 kg): 90 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults 30–33 kg): 80 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults 26–29 kg): 70 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults 22–25 kg): 60 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults 18–21 kg): 50 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults 14–17 kg): 40 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults 10–13 kg): 30 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults 8–9 kg): 20 mg twice daily until disease progression or unacceptable toxicity.

Adjuvant Treatment of Unresectable/Metastatic Melanoma

• PO (Adults): 150 mg twice daily; continue until disease recurrence or unacceptable toxicity for up to 1 yr.
Tablets for Oral Suspension
• PO (Adults 51 kg): 150 mg twice daily until disease progression or unacceptable toxicity for up to 1 yr.
• PO (Adults 46–50 kg): 130 mg twice daily until disease progression or unacceptable toxicity for up to 1 yr.
• PO (Adults 42–45 kg): 110 mg twice daily until disease progression or unacceptable toxicity for up to 1 yr.
• PO (Adults 38–41 kg): 100 mg twice daily until disease progression or unacceptable toxicity for up to 1 yr.
• PO (Adults 34–37 kg): 90 mg twice daily until disease progression or unacceptable toxicity for up to 1 yr.
• PO (Adults 30–33 kg): 80 mg twice daily until disease progression or unacceptable toxicity for up to 1 yr.
• PO (Adults 26–29 kg): 70 mg twice daily until disease progression or unacceptable toxicity for up to 1 yr.
• PO (Adults 22–25 kg): 60 mg twice daily until disease progression or unacceptable toxicity for up to 1 yr.
• PO (Adults 18–21 kg): 50 mg twice daily until disease progression or unacceptable toxicity for up to 1 yr.
• PO (Adults 14–17 kg): 40 mg twice daily until disease progression or unacceptable toxicity for up to 1 yr.
• PO (Adults 10–13 kg): 30 mg twice daily until disease progression or unacceptable toxicity for up to 1 yr.
• PO (Adults 8–9 kg): 20 mg twice daily until disease progression or unacceptable toxicity for up to 1 yr.

Treatment of Unresectable/Metastatic Solid Tumors

• PO (Adults): 150 mg twice daily until disease progression or unacceptable toxicity.
• PO (Children 1 yr and 51 kg): 150 mg twice daily until disease progression or unacceptable toxicity.
• PO (Children 1 yr and 38–50 kg): 100 mg twice daily until disease progression or unacceptable toxicity.
• PO (Children 1 yr and 26–37 kg): 75 mg twice daily until disease progression or unacceptable toxicity.
Tablets for Oral Suspension
• PO (Adults and Children 1 yr and 51 kg): 150 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults and Children 1 yr and 46–50 kg): 130 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults and Children 1 yr and 42–45 kg): 110 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults and Children 1 yr and 38–41 kg): 100 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults and Children 1 yr and 34–37 kg): 90 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults and Children 1 yr and 30–33 kg): 80 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults and Children 1 yr and 26–29 kg): 70 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults and Children 1 yr and 22–25 kg): 60 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults and Children 1 yr and 18–21 kg): 50 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults and Children 1 yr and 14–17 kg): 40 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults and Children 1 yr and 10–13 kg): 30 mg twice daily until disease progression or unacceptable toxicity.
• PO (Adults and Children 1 yr and 8–9 kg): 20 mg twice daily until disease progression or unacceptable toxicity.

Treatment of Low-Grade Glioma

• PO (Children 1 yr and 51 kg): 150 mg twice daily until disease progression or unacceptable toxicity.
• PO (Children 1 yr and 38–50 kg): 100 mg twice daily until disease progression or unacceptable toxicity.
• PO (Children 1 yr and 26–37 kg): 75 mg twice daily until disease progression or unacceptable toxicity.
Tablets for Oral Suspension
• PO (Children 1 yr and 51 kg): 150 mg twice daily until disease progression or unacceptable toxicity.
• PO (Children 1 yr and 46–50 kg): 130 mg twice daily until disease progression or unacceptable toxicity.
• PO (Children 1 yr and 42–45 kg): 110 mg twice daily until disease progression or unacceptable toxicity.
• PO (Children 1 yr and 38–41 kg): 100 mg twice daily until disease progression or unacceptable toxicity.
• PO (Children 1 yr and 34–37 kg): 90 mg twice daily until disease progression or unacceptable toxicity.
• PO (Children 1 yr and 30–33 kg): 80 mg twice daily until disease progression or unacceptable toxicity.
• PO (Children 1 yr and 26–29 kg): 70 mg twice daily until disease progression or unacceptable toxicity.
• PO (Children 1 yr and 22–25 kg): 60 mg twice daily until disease progression or unacceptable toxicity.
• PO (Children 1 yr and 18–21 kg): 50 mg twice daily until disease progression or unacceptable toxicity.
• PO (Children 1 yr and 14–17 kg): 40 mg twice daily until disease progression or unacceptable toxicity.
• PO (Children 1 yr and 10–13 kg): 30 mg twice daily until disease progression or unacceptable toxicity.
• PO (Children 1 yr and 8–9 kg): 20 mg twice daily until disease progression or unacceptable toxicity.

Tafinlar

• Inhibits kinase, an enzyme that promotes cell proliferation.

• Decreased spread/progression of melanoma, NSCLC, anaplastic thyroid cancer, low-grade gliomas, and other solid tumors.

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Absorption: Well absorbed (95%) following oral administration.

Distribution: Unknown.

Protein Binding: 99.7%.

Metabolism/Excretion: Mostly metabolized by the CYP2C8 and CYP3A4 isoenzymes; two metabolites (hydroxy-dabrafenib and desmethyl-1–dabrafenib) have antineoplastic activity. Excreted as metabolites in feces (72%) and urine (23%).

Half-life: Dabrafenib: 8 hr; hydroxy-dabrafenib: 10 hr, desmethyl-1–dabrafenib: 21–22 hr.

(progression-free survival)

• Instruct patient to take dabrafenib as directed at least 1 hr before or 2 hr after meals. Take missed doses as soon as remembered unless within 6 hr of next dose; then skip missed dose and take regularly scheduled dose. If vomiting occurs after administration, do not take an additional dose. Take next dose at the scheduled time. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
• Inform patient that dabrafenib increases risk of developing new cutaneous malignancies. Notify health care professional immediately if new lesions (wart, skin sore, or reddish bump that bleeds or does not heal) or changes in size or color of existing moles or lesions occur.
• Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort.
• Inform patient of potential side effects. Advise patient to notify health care professional if fever, signs and symptoms of hyperglycemia (increased thirst, urinating more often than normal, breath smells like fruit), eye problems (blurred vision, loss of vision, vision changes, see color dots, halo [see blurred outline around objects], eye pain, swelling, redness), bleeding (headaches, dizziness, feeling weak, coughing up blood or blood clots, vomiting blood or vomit looks like coffee grounds, red or black tarry stool), skin reactions (blisters or peeling of skin, blisters on lips or around mouth or eyes, mouth sores, high fever or flu-like symptoms, enlarged lymph nodes), thromboembolism, or HF (heart pounding or racing, shortness of breath, swelling of ankles and feet, light-headedness) occur.
• Rep: Advise females of reproductive potential and males (including those who have had vasectomies) with female partners of reproductive potential to use a highly effective form of contraception during and for at least 2 wk after last dose of dabrafenib. Use a nonhormonal form of contraception; dabrafenib may decrease effectiveness of hormonal contraceptives. Advise patient to notify health care professional if pregnancy is suspected and to avoid breastfeeding during therapy and for 2 wk after last dose. Advise patients to seek counseling on fertility and family planning before beginning therapy; may permanently impair fertility in females and males.

da-BRAF-e-nib

NDC Code^*

• 0078- Novartis Pharmaceuticals Corporation
  • 0078-0681- Tafinlar
    • 0078-0681-66- 120 CAPSULE in 1 BOTTLE (0078-0681-66)

• 0078- Novartis Pharmaceuticals Corporation
  • 0078-0682- Tafinlar
    • 0078-0682-66- 120 CAPSULE in 1 BOTTLE (0078-0682-66)