Names and pronunciation
(da-braf′e-nib) Tafinlar
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Drug reference
(da-braf′e-nib) Tafinlar
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Func. class.: Antineoplastic
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Chem. class.: Signal transduction inhibitor, kinase inhibitor
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ACTION: Inhibits kinase, inhibitor against mutated forms of BRAF kinases in melanoma cells
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USES: Unresectable or metastatic BRAF V600E-mutated malignant mela- noma or V600K-mutated melanoma in combination with tramatinib
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CONTRAINDICATIONS: Preg- nancy, hypersensitivity Precautions: Breastfeeding, children, infection, dehydration, diabetes mellitus, fever, G6PD deficiency, hemolytic ane- mia, hyperglycemia, hypotension, infer- tility, iritis, renal failure, secondary malignancy
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SIDE EFFECTS CNS: Headache, fever, fatigue GI: Pancreatitis INTEG: Rash, alopecia MISC: Myalgia OTHER: Hyperglycemia, hypophosphate- mia, hyponatremia, secondary malig- nancy, hand/foot syndrome CV: Cardiomyopathy, HF, thromboembolism EENT: Uveitis, retinal detachment
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INTERACTIONS Altered: dabrafenib concentrations— CYP3A4 inhibitors (ketoconazole, itra- conazole, erythromycin, clarithromycin) Decrease: dabrafenib concentrations— CYP3A4 inducers (dexamethasone, phe- nytoin, carBAMazepine, rifAMPin, PHE- Nobarbital), antacids, proton pump inhibitors Decrease: effect of CYP3A4, CYP2C9 substrates Drug/Herb Decrease: dabrafenib concentrations— St. John’s wort Drug/Food Test Increase: dabrafenib effect—grapefruit juice; avoid use while taking product
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DOSAGE AND ROUTES • Adult: PO 150 mg q12hr until disease progression; avoid strong CYP3A4/ CYP2C8 inhibitors or inducers
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Available forms: Capsules 50, 75 mg
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Administer: PO route • Obtain testing for genetic evidence of BRAF V60E or K • Swallow whole; do not open, crush, chew capsules • If dose is missed, take within 6 hr of missed dose; if >6 hr have passed, skip dose • Space doses q12hr • Take at least 1 hr prior to or 2 hr after a meal
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Assess: • Secondary malignancy: perform a dermatologic evaluation before therapy, q2mo while on therapy, and for up to 6 mo after discontinuing • Serious fever and febrile reaction: hypotension, rigors/chills, dehydration, renal failure; fever occurs when given with trametinib. Interruption of therapy, a dose reduction, or permanent therapy discontinuation may be needed. Monitor for signs and symptoms of infection. If severe, monitor renal function (BUN/se- rum creatinine) during and after and give antipyretics when therapy is resumed. In a febrile reaction that does not resolve within 3 days, give corticosteroids (pred- niSONE 10 mg/day PO) for at least 5 days; ensure that there is no evidence of active infection prior to starting cortico- steroids • Hyperglycemia: Monitor serum glu- cose levels at baseline and as clinically indicated • Uveitis, iritis, and iridocyclitis: ste- roid and mydriatic ophthalmic drops may provide relief for these conditions. Monitor for visual signs and symptoms of uveitis (blurred vision, photophobia, and eye pain). Continue at the same dose in iritis. Hold for mild or moderate uveitis that does not re- spond to ocular therapy, severe uveitis, or iridocyclitis; initiate treatment as indi- cated. Permanently discontinue in those who develop persistent grade 2 or higher uveitis that lasts longer than 6 wk • Bleeding: major intracranial bleeding/ GI bleeding can occur when used with trametinib. Monitor for signs of bleeding (frank blood; blood in stools, urine, vomit); evaluate any fall in hematocrit, hypoten- sion, grade 3 bleeding, hold product; grade 4, discontinue • Cardiomyopathy: a decrease in left ventricular ejection fraction (LVEF) ≥10% from baseline and below the lower limit of normal (LLN) was higher when given in combination with trametinib. Obtain an ECG or MUGA prior to starting combination therapy, 1 mo after starting dabrafenib, and then q2-3mo during treatment. Hold dab- rafenib for symptomatic CHF or LVEF below the LLN with an absolute decrease of >20% from baseline. Resume at the same dose if LVEF improves to the institutional LLN and an absolute decrease of 10% or less from baseline • Palmar-plantar erythrodysesthesia syndrome (hand and foot syndrome): may occur when given with trametinib, usually within 37 days; hospitalization may be required due to a secondary in- fection of the skin. Interruption of therapy, a dose reduction, or permanent therapy discontinuation may be needed in those who develop severe skin toxicity
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Evaluate: • Therapeutic response: decrease in melanoma progression
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To notify prescriber of new lesions • To notify providers of all OTC, Rx, herbal products taken • To take as prescribed 1 hr prior to or 2 hr after meals, to take a missed dose at least 6 hr before next dose • To report adverse reactions immediately • About reason for treatment, expected results • Advise patients to report symptoms of severe hyperglycemia (excessive thirst, increased urinary frequency) • Advise that other malignancies are possible • Pregnancy: to use effective nonhor- monal contraception during treatment and for at least 30 days after discontinu- ing treatment; not to breastfeed HIGH ALERT D
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PHARMACOKINETICS Protein binding 99.7%, half-life 8 hr (dabrafenib), 10 hr, 21-22 hr metabo- lites, excreted 71% (feces), 23% (urine)
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• Adult: PO 150 mg q12hr until disease progression; avoid strong CYP3A4/ CYP2C8 inhibitors or inducers
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