Products
Vemurafenib was approved in 2011 in film-coated tablet form (Zelboraf).
Structure and properties
Vemurafenib (C23H18ClF2N3O3S, Mr = 489.9 g/mol) is a white, crystalline substance that is practically insoluble in water.
Effects
Vemurafenib (ATC L01XE15) has antitumor and antiproliferative properties. It reduces mortality and increases survival. The properties are based on inhibition of the mutant serine threonine kinase BRAF V600E. Mutations in the -gene cause activation of the kinase, which leads to cell proliferation. V600E refers to the replacement of a single amino acid at position 600: valine is replaced by glutamic acid. This mutation increases the activity of the enzyme by a factor of 500.
Indications
For the treatment of melanoma with the BRAFV600E mutation that cannot be removed by surgery or that is metastatic. The mutation must be detected by a drug agency-approved test. Roche offers this test commercially (cobas 4800 BRAF V600).
Dosage
According to the SmPC. The usual dose is 960 mg divided into two doses in the morning and evening, approximately 12 hours apart. It may be taken with or without food. Because of the possibility of photosensitization, good sun protection is necessary during treatment.
Contraindications
- Hypersensitivity
For complete precautions, see the drug label.
Interactions
Vemurafenib is a moderate CYP1A2 inhibitor, a weak CYP2D6 inhibitor, an inducer of CYP3A4, and a substrate of CYP3A4. Appropriate drug-drug interactions must be considered.
Adverse effects
The most common potential adverse effects include joint pain, rash, hair loss, fatigue, photosensitization, nausea, pruritus, and papillomas. Vemurafenib may lead to squamous cell carcinoma formation and prolong the QT interval.
