dabrafenib

High Alert

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).

Drug-drug:

Strong CYP3A4 inhibitors or strong CYP2C8 inhibitors, including ketoconazole, nefazodone, clarithromycin, and gemfibrozil, may ↑ levels and ↑ risk of toxicity; avoid concurrent use.
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 effectiveness; avoid concurrent use.

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

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

Adjuvant Treatment of Unresectable/Metastatic Melanoma

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

Treatment of Unresectable/Metastatic Solid Tumors

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

Treatment of Low-Grade Glioma

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

Inhibits kinase, an enzyme that promotes cell proliferation.

Therapeutic effects:

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)

ROUTE		ONSET		PEAK		DURATION
PO		within 1 mo		1–2 mo		8 mo

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Take missed dose as soon as remembered unless within 6 hr of next dose; then omit and take regularly scheduled dose. If vomiting occurs after administration, do not take additional dose.
Inform patient that dabrafenib ↑ risk of developing new cutaneous malignancies and to notify health care provider 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 provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications, especially St. John’s wort.
Advise patient to notify health care provider if fever; ↑ thirst, appetite, or urination; fruity breath; visual changes; eye pain or swelling; ↑ bleeding; skin blisters, sores, or peeling; high fever; flu-like symptoms; enlarged lymph nodes; or HF occur.
Rep: Advise women of reproductive potential and men (including those who have had vasectomies) with female partners of reproductive potential to use a highly effective nonhormonal contraception during and for ≥2 wk after last dose. Dabrafenib may ↓ effectiveness of hormonal contraceptives. Advise patient to notify health care provider if pregnancy is suspected and to avoid breastfeeding during 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 both sexes.

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Indications ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Availability ⬆ ⬇

Route/Dosage ⬆ ⬇

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Classifications ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Pronunciation ⬆