• Unresectable or metastatic melanoma with BRAF ^V600E mutation.
• Erdheim-Chester disease ECD with BRAF ^V600E mutation.

Contraindicated in:

• Underlying electrolyte abnormalities (↑ risk of serious arrhythmias; correct prior to administration)
• Congenital or acquired prolonged QT syndromes
• Baseline QTc interval >500 msec
• Concurrent use of QT-interval prolonging drugs
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Severe renal impairment
• Severe hepatic impairment
• Receiving radiation therapy prior to, during, or after therapy (↑ risk of radiation sensitization/recall)
• Rep: Women of reproductive potential
• Pedi: Safety and effectiveness not established in children
• Geri: ↑ risk of cutaneous squamous cell carcinoma, nausea, ↓ appetite, peripheral edema, keratoacanthoma, and atrial fibrillation in older adults.

CV: peripheral edema, QT interval prolongation, TORSADES DE POINTES.

Derm: alopecia, dry skin, photosensitivity (↑ in females), pruritus, rash (↑ in females), skin cancer, skin papilloma, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), keratocanthoma (↑ in males), STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN).

EENT: iritis, retinal vein occlusion, uveitis.

GI: ↓ appetite, HEPATOTOXICITY, nausea.

GU: ↑ serum creatinine (↑ in females), acute interstitial nephritis, acute tubular necrosis.

MS: arthralgia (↑ in females), myalgia, Dupuytren’s contracture, back pain, pain, plantar fascial fibromatosis.

Neuro: fatigue, weakness, dysgeusia, headache.

Resp: cough.

Misc: fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), radiation sensitization/recall.

Drug-Drug:

• QT interval prolonging drugs may ↑ the risk of QT interval prolongation with arrhythmias; concurrent use contraindicated.
• Concurrent use with CYP1A2 substrates with narrow therapeutic indices not recommended. Consider dose ↓ of substrates.
• Strong CYP3A inhibitors, including atazanavir, clarithromycin, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, and voriconazole, may ↑ levels and the risk of toxicity; avoid concurrent use; if concurrent use is necessary, consider ↓ vemurafenib dose.
• Strong CYP3A inducers, including carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and rifapentine, may ↓ levels and effectiveness; avoid concurrent use; if concurrent use necessary, ↑ vemurafenib dose.
• May ↑ risk of bleeding with warfarin.
• Concurrent use with ipilimumab may ↑ risk of hepatotoxicity
• May ↑ digoxin levels and the risk of toxicity

• Tablets: 240 mg;

• PO (Adults): 960 mg (4 tablets) twice daily until disease progression or unacceptable toxicity; Concurrent use of strong CYP3A4 inducers: 1200 mg (5 tablets) twice daily until disease progression or unacceptable toxicity.

Zelboraf

• Inhibits mutated forms of the enzyme kinase. Inhibits proliferation that occurs in conjunction with activated BRAF proteins.

• Decreased spread of melanoma and Erdheim-Chester disease.

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors

Absorption: Some absorption follows oral administration; bioavailability is not known.

Distribution: Widely distributed to tissues.

Protein Binding: >99%.

Metabolism/Excretion: Mostly metabolized by the liver via the CYP3A4 isoenzyme system; primarily excreted in the feces, with 1% eliminated in urine.

Half-life: 57 hr.

(plasma concentrations)

• Instruct patient to take vemurafenib as directed. If vomiting occurs, do not an additional dose; take next dose as scheduled. Take missed doses as soon as remembered up to 4 hr before next dose; do not double dose.
• Inform patient that assessment of BRAF mutation is required for selection of patients.
• Instruct patient to stop taking vemurafenib and notify health care professional immediately if signs and symptoms of allergic reaction (rash or redness all over body; feeling faint; difficulty breathing or swallowing; throat tightness or hoarseness; fast heartbeat; swelling of face, lips, or tongue) or severe skin reactions (blisters on skin; blisters or sores in mouth; peeling of skin, fever, redness or swelling of face, hands, or soles of feet) occur.
• Advise patient to wear broad spectrum UVA/UVB sunscreen, lip balm (SPF ≥30), and protective clothing, and to avoid sun exposure to prevent photosensitivity reactions. Severe photosensitivity reactions may require dose modifications.
• Advise patient to notify health care professional if signs and symptoms of liver dysfunction (yellow skin or whites of eyes; feeling tired; urine turns dark or brown; nausea or vomiting; loss of appetite; pain on right side of stomach) or eye problems (eye pain, swelling, or redness; blurred vision; vision changes) occur.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
• Inform patient that regular assessments of skin and assessments for signs and symptoms of other malignancies must be done during and for up to 6 mo after therapy. Advise patient to notify health care professional immediately if any changes in skin occur.
• Rep: Advise women of reproductive potential to use effective contraception during and for at least 2 wk after last dose of vemurafenib, and to avoid breastfeeding during and for 2 wk after last dose.

vem-u-RAF-e-nib

NDC Code^*

• 50242- Genentech, Inc.
  • 50242-090- ZELBORAF
    • 50242-090-02- 1 BOTTLE, PLASTIC in 1 CARTON (50242-090-02) > 112 TABLET, FILM COATED in 1 BOTTLE, PLASTIC

• 50242- Genentech, Inc.
  • 50242-090- ZELBORAF
    • 50242-090-86- 1 BOTTLE, PLASTIC in 1 CARTON (50242-090-86) > 112 TABLET, FILM COATED in 1 BOTTLE, PLASTIC