Products
Vismodegib is commercially available in capsule form (Erivedge). The drug was newly approved in many countries in May 2013.
Structure and properties
Vismodegib (C19H14Cl2N2O3S, Mr = 421.3 g/mol) is a chlorinated methylsulfonylbenzamide derivative and exists as a white to brownish powder.
Effects
Vismodegib (ATC L01XX43) has antitumor properties. The effects are due to inhibition of the Hedgehog signaling pathway by binding to the membrane protein Smoothened. This leads to transcriptional inhibition of genes involved in tumor growth.
Indications
For the treatment of patients with advanced or metastatic basal cell carcinoma. Use in other tumors is being investigated.
Dosage
According to the SmPC. Capsules are taken once daily, independent of meals. Vismodegib has a long half-life of several days.
Contraindications
- Hypersensitivity
- Vismodegib is embryotoxic and teratogenic and therefore must not be used in pregnant women or women of childbearing potential.
For complete precautions, see the drug label.
Interactions
Vismodegib is excreted predominantly unchanged. Although it is a substrate of CYP2C9 and CYP3A4 in vitro, it does not appear to interact with CYP to any relevant extent in vivo. Vismodegib is a substrate of P-glycoprotein. Co-administration with P-gp inhibitors increases plasma concentrations and increases the risk of adverse effects. Reduced levels should be expected with an increase in gastric pH.
Adverse effects
The most common potential adverse effects include muscle spasms, hair loss, taste disturbances, weight loss, fatigue, nausea, diarrhea, poor appetite, constipation, joint pain, and vomiting.
