Vemurafenib

What it is and how it works

Mechanism of Action Vemurafenib is a low molecular weight, orally available inhibitor of some mutated forms of BRAF serine- threonine kinase, including BRAF V600E. Vemurafenib also inhibits other kinases in vitro such as CRAF, ARAF, wild-type BRAF, SRMS, ACK1, MAP4K5, and FGR at similar concentrations. Some mutations in the BRAF gene including V600E result in constitutively activated BRAF proteins, which can cause cell proliferation in the absence of growth factors that would normally be required for proliferation. Vemurafenib has anti-tumor effects in cellular and animal models of melanomas with mutated BRAF V600E.

Mechanism class: Protein Kinase Inhibitors · Cytochrome P450 1A2 Inhibitors · P-Glycoprotein Inhibitors

Indications

® is a kinase inhibitor indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. ( 1.1 , 2.1 ) ZELBORAF ® is indicated for the treatment of patients with Erdheim- Chester Disease with BRAF V600 mutation. ( 1.2 , 2.1 ) Limitation of Use: ZELBORAF is not indicated for treatment of patients with wild-type BRAF melanoma ( 2.1 , 5.2 ) Unresectable or Metastatic Melanoma ZELBORAF ® is indicated for the treatment of patients with unresectable or metastatic melanoma with BRAF V600E mutation as detected by an FDA-approved test. Limitation of Use: ZELBORAF is not indicated for treatment of patients with wild-type BRAF melanoma . Erdheim-Chester Disease ZELBORAF ® is indicated for the treatment of patients with Erdheim-Chester Disease (ECD) with BRAF V600 mutation.

Dosage and administration (summary)

Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with ZELBORAF. Recommended dose: 960 mg orally twice daily taken approximately 12 hours apart with or without a meal. Patient Selection for Treatment of Melanoma Confirm the presence of BRAF V600E mutation in melanoma tumor specimens prior to initiation of treatment with ZELBORAF . Information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma is available at http://www.fda.gov/CompanionDiagnostics. Recommended Dose The recommended dose of ZELBORAF is 960 mg (four 240 mg tablets) orally every 12 hours with or without a meal.

Contraindications

None. None

Warnings and precautions

New Primary Cutaneous Malignancies: Perform dermatologic evaluations prior to initiation of therapy, every 2 months while on therapy, and for up to 6 months following discontinuation of ZELBORAF. Manage with excision and continue treatment without dose adjustment. New Non-Cutaneous Squamous Cell Carcinoma: Evaluate for symptoms or clinical signs of new non-cutaneous SCC before initiation of treatment and periodically during treatment. Other Malignancies: Monitor patients receiving ZELBORAF closely for signs or symptoms of other malignancies .

Pregnancy

Pregnancy Risk Summary Based on its mechanism of action, ZELBORAF can cause fetal harm when administered to a pregnant woman . There are no available data on the use of ZELBORAF in pregnant women to determine the drug-associated risk; however, placental transfer of vemurafenib to a fetus has been reported.

Storage and supply

Storage and Stability: Store at room temperature 20°C–25°C (68°F–77°F); excursions permitted between 15°C and 30°C (59°F and 86°F), See USP Controlled Room Temperature. Store in the original container with the lid tightly closed.

Source: Vemurafenib (Zelboraf) — US FDA prescribing information, 2026-08-28, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.