Pregnancy Category: D
Pharmacologic: kinase inhibitors
Pharmacologic: kinase inhibitors
Treatment of metastatic/unresectable melanoma in patients with the BRAF V600E mutation.
Inhibits kinase, an enzyme that promotes cell proliferation
Decreased spread/progression of melanoma
Absorption: Well absorbed (95%) following oral administration
Protein Binding: 99.7%
Metabolism and Excretion: Mostly metabolized by CYP 2C8 and CYP3A4 enzyme systems, 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—21–22hr
Time/action profile (progression-free survival)
|PO||within 1 mo||1–2 mo||8 months|
Contraindicated in: Obstetric: Pregnancy (may cause fetal harm) Lactation: Breast feeding should be avoidedConcurrent use of CYP 3A4/CYP2C8 inhibitors or inducers (may significantly alter levels and effects)
Use Cautiously in: BRAF Wild-type melanoma (may increase proliferation)genetic implication History of Glucose-6–Phosphate Dehydrogenase Deficiency (may cause hemolytic anemia)Moderate to severe hepatic impairment (blood levels may be ↑)Moderate to severe renal impairment Obstetric: Patients with reproductive potential (hormonal contraceptives may be less effective, additional methods required) Pediatric: Safe and effective use in children has not been established
Adverse Reactions/Side Effects
Central nervous system
- headache (most frequent)
Ear, Eye, Nose, Throat
- cough (most frequent)
- alopecia (most frequent)
- hyperkeratosis (most frequent)
- palmar-plantar erythrodysesthesia (most frequent)
- papilloma (most frequent)
- cutaneous squamous cell carcinoma
Fluid and Electrolyte
- hypophosphatemia (most frequent)
- arthralgia (most frequent)
- back pain (most frequent)
- myalgia (most frequent)
- fever including serious febrile reactions
- ↑ alkaline phosphatase
- tumor promotion
Drug-Drug interactionConcurrent use of strong inhibitors of CYP3A4 or CYP2C8, including ketoconazole, nefazodone, clarithromycin and gemfibrozil ↑ blood levels and the risk of toxicity and should be avoided. Careful monitoring for toxicity is required. Concurrent use of strong inducers of CYP3A4 or CYP2C8 including carbamazepine, phenobarbital, phenytoin, and rifampin ↓ blood levels and may ↓ effectiveness. Careful monitoring for decreased results is required.Drugs that ↑ gastric pH including antacids, H2– receptor antagonists and proton pump inhibitors may ↓ blood levels and effectivenessMay ↓ effectiveness of other drugs that are substrates of CYP3A4, CYP2C8, CYP2C9, CYP2C19 or CYP2B6 including midazolam.St. John's wort↓ blood levels and may ↓ effectiveness; concurrent use should be avoided.
Oral (Adults) 150 mg twice daily, continued until disease progression or unacceptable toxicity. Dose modifications recommended for various levels of related toxicities.
Capsules: 50 mg, 75 mg
- Perform skin examinations prior to starting therapy and every 2 months during and for 6 months after completion of therapy
- Monitor temperature. If fever is 101.3°F to 104°F, withhold drabafenib until fever resolves, then resume at same dose. If fever is >104°F or complicated by rigors, hypotension, dehydration, or renal failure, withhold until fever resolves, then resume at a reduced dose. For first reduction, decrease dose to 100 mg twice daily. For second dose reduction, decrease dose to 75 mg twice daily. For third dose reduction, decrease dose to 50 mg twice daily. If unable to tolerate 50 mg twice daily, discontinue dabrafenib.
- Monitor for signs and symptoms of uveitis (change in vision, photophobia, eye pain). May require steroid and mydriatic ophthalmic drops.
- Lab Test Considerations: May cause hyperglycemia requiring increase in dose of or initiation of insulin or oral hypoglycemic agents. Monitor serum glucose levels in patients with pre-existing diabetes or hyperglycemia.
- May cause hypophosphatemia, ↑alkaline phosphatase, and hyponatremia.
- Monitor for hemolytic anemia in patients with glucose-6–phosphate dehydrogenase (G6PD) deficiency.
Potential Nursing DiagnosesImpaired skin integrity (Indications)
- Evidence of BRAF V600E mutation status must be confirmed prior to starting therapy with dabrafenib.
- Oral: Administer twice daily about 12 hrs apart. Administer on an empty stomach at least 1 hr before or 2 hrs after a meal. Swallow capsules whole; do not open, crush, break, or chew.
- Instruct patient to take dabrafenib as directed at least 1 hr before or 2 hrs after meals. Take missed doses as soon as remembered unless within 6 hrs of next dose, then skip missed dose and take regularly scheduled dose.
- 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.
- 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.
- 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), or eye problems (eye pain, swelling, redness, blurred visions or other changes in vision) occur.
- Advise female patient to use a highly effective form of contraception during and for at least 4 months after treatment. Use a non-hormonal 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. Advise male patients to seek counseling on fertility and family planning prior to beginning therapy; may cause spermatogenesis.
- Decrease in progression of malignant melanoma.
Drug Guide, © 2015 Farlex and Partners