Information for Patients / Medical Professionals

Zelboraf® (vemurafenib)

• Full Prescribing Information
• Material Safety Data Sheet

Indication

ZELBORAF™ (vemurafenib) is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAFV600E mutation as detected by an FDA-approved test.

ZELBORAF is not recommended for use in patients with wild-type BRAF melanoma.

Important Safety Information

Cutaneous squamous cell carcinoma (cuSCC)

• The incidence of cuSCC, including both SCCs of the skin and keratoacanthomas, was 24%.
• Perform dermatologic evaluations prior to initiation of therapy, every 2 months while on therapy, and potentially for 6 months after therapy. Any suspicious skin lesions should be excised, evaluated, and treated as per standard of care.

Hypersensitivity and Dermatologic Reactions

• Serious hypersensitivity reactions, including anaphylaxis, generalized rash and erythema, or hypotension, have been reported in association with ZELBORAF and upon re-initiation of treatment.
• Severe dermatologic reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported.
• In patients who experience a severe hypersensitivity or dermatologic reaction, ZELBORAF treatment should be permanently discontinued.

QT prolongation

• Exposure-dependent QT prolongation has been reported, which may lead to an increased risk for ventricular arrhythmias, including Torsade de Pointes.
• Treatment is not recommended in patients with uncorrectable electrolyte abnormalities, with long QT syndrome, or who are taking medicines known to prolong the QT interval.
• Monitor ECG and electrolytes before treatment and after dose modification. Monitor ECGs at day 15, monthly during the first 3 months of treatment, every 3 months thereafter, or more often as clinically indicated.
• If the QTc exceeds 500 ms, temporarily interrupt ZELBORAF, correct electrolyte abnormalities, and control cardiac risk factors for QT prolongation. Re-initiate treatment at a lower dose once the QTc decreases below 500 ms. Permanent discontinuation is recommended if, after correction of associated risk factors, the QTc increase meets both a value of >500 ms and >60 ms change from pre-treatment values.

Liver laboratory abnormalities

• Liver laboratory abnormalities have occurred.
• Monitor liver enzymes and bilirubin before initiation of treatment and monthly during treatment, or as clinically indicated. Manage lab abnormalities with dose reduction, treatment interruption, or treatment discontinuation.

Photosensitivity

• Mild to severe photosensitivity has been reported.
• Advise patients to avoid sun exposure and use adequate sun protection. For intolerable grade 2 or greater photosensitivity, dose modifications are recommended.

Ophthalmologic Reactions

• Serious ophthalmologic reactions, including uveitis and retinal vein occlusion, have been reported.
• Treatment with steroid and mydriatic ophthalmic drops may be required to manage uveitis. Routinely monitor patients for uveitis.
• Additionally, blurry vision, iritis, and photophobia were observed.

New Primary Malignant Melanoma

• New primary melanomas were reported in the Phase III study.
• Cases were managed with excision and patients continued treatment without dose adjustment; monitor for skin lesions as outlined above [see cuSCC].

Use in Pregnancy: Pregnancy Category D

• Apprise patients who are pregnant or who may become pregnant that ZELBORAF may cause fetal harm.

BRAF Testing

• Confirmation of BRAFV600E(+) melanoma is required for appropriate patient selection. The efficacy and safety of ZELBORAF have not been studied in patients with wild-type BRAF melanoma.

Most common adverse events

• The most common (≥30%) adverse reactions of any grade reported were arthralgia, rash, alopecia, fatigue, photosensitivity reaction, nausea, pruritus, and skin papilloma.
• The most common (≥5%) grade 3 adverse reactions were cuSCC and rash. In clinical studies, cuSCC was predefined as a grade 3 event.

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.

Please see the full Prescribing Information for additional important safety information at www.zelboraf.com.