威罗菲尼片（Zelboraf）Vemurafenib

Vemurafenib tablets (Zelboraf) are a kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma detected by an FDA-approved test for BRAFV600E mutations.

[Model and Specifications]

Film-coated tablets: 240 mg

[Usage and Dosage]

(1) Recommended dose: 960 mg orally, bid.

(2) Administer ZELBORAF at approximately 12-hour intervals with or without meals.

(3) ZELBORAF should be swallowed whole with a glass of water. ZELBORAF should not be chewed or crushed.

(4) Treatment of symptomatic adverse drug reactions may require dose reduction, interruption of treatment, or discontinuation of ZELBORAF treatment. Dose reduction to a dose below 480 mg is not recommended.

[Precautions]

(1) Cutaneous squamous cell carcinoma (cuSCC) occurred in 24% of patients. Perform dermatological evaluation before treatment and every 2 months while on treatment. No dose adjustment is required for excisional treatment and continued treatment.
(2) Severe hypersensitivity reactions, including anaphylaxis, have been reported during treatment and upon restarting treatment. Discontinue ZELBORAF in patients who experience severe hypersensitivity reactions.

(3) Severe dermatologic reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported. Discontinue treatment in patients who experience severe dermatologic reactions.

(4) QT prolongation has been reported. Monitor ECG and electrolytes prior to treatment and after dose adjustments. Monitor ECGs on day 15, every 3 months during the first 3 months of treatment, and every 3 months thereafter, or more frequently as clinically indicated. If QTc exceeds 500 ms, briefly interrupt ZELBORAF, correct electrolyte abnormalities, and manage risk factors for QT prolongation.

(5) Liver laboratory abnormalities may occur. Monitor liver enzymes and bilirubin prior to starting treatment and monthly during treatment, or as clinically indicated.

(6) Photosensitivity has been reported. Advise patients to avoid sunlight exposure while taking ZELBORAF.
(7) Serious ophthalmic reactions have been reported, including uveitis, iritis, and retinal vein occlusion. Monitor patients routinely for ophthalmic reactions.

(8) New primary malignant melanomas have been reported. Treat with excision, and continue treatment without dose adjustment. Perform dermatological monitoring as described above.

(9) Pregnancy: May cause fetal harm. Advise women of the potential risk to the fetus.

(10) To select patients for ZELBORAF treatment, use an FDA-approved test for BRAF mutations. The efficacy and safety of ZELBORAF have not been studied in patients with wild-type BRAF melanoma.

[Adverse Reactions and Contraindications]
The most common adverse reactions (≥ 30%) are arthralgia, rash, alopecia, fatigue, photosensitivity, nausea, pruritus, and skin papilloma.

[Contraindications]
Limitations of use: ZELBORAF is not recommended in patients with wild-type BRAF melanoma.

[Pregnant women use]
Breastfeeding mothers: Discontinue breastfeeding while receiving ZELBORAF

[Drug interactions]
(1) CYP substrates: It is not recommended to use ZELBORAF with drugs that are metabolized by CYP3A4, CYP1A2, or CYP2D6 with a narrow therapeutic window. If co-administration cannot be avoided, use caution and consider reducing the dose of the concomitant CYP1A2 or CYP2D6 substrate drug.
(2) ZELBORAF may increase exposure to concomitantly administered warfarin. Use caution and consider additional INR monitoring when ZELBORAF is used concomitantly with warfarin.