Products
Dabrafenib was approved in the US and EU in 2013 and in many countries in 2014 in hard capsule form (Tafinlar).
Structure and properties
Dabrafenib (C23H20F3N5O2S2, Mr = 519.6 g/mol) is present in drugs as dabrafenib mesilate, a white to slightly colored powder that is practically insoluble in water. It is a thiazole and pyrimidine derivative.
Effects
Dabrafenib (ATC L01XE23) has antitumor and antiproliferative properties. The effects are due to inhibition of the mutant serine threonine kinase BRAF V600E. Mutations in the BRAF 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 patients with nonresectable or metastatic melanoma with diagnostically confirmed BRAF V600E mutation.
Dosage
According to the SmPC. Capsules are taken twice daily, 12 hours apart and fasting, at least one hour before or two hours after a meal.
Contraindications
- Hypersensitivity
For complete precautions, see the drug label.
Interactions
Dabrafenib is metabolized by CYP2C8 and CYP3A4. Corresponding drug-drug interactions are possible. Drugs that alter gastric pH may decrease the bioavailability of dabrafenib.
Adverse Effects
The most common potential adverse effects include hyperkeratosis, headache, fever, muscle and joint pain, papillomas, hair loss, vomiting, rash, and hand-foot syndrome.