Vismodegib — Drug Monograph
Brand names: Erivedge
Drug class: Other
Mechanism of Action
Vismodegib is a small-molecule inhibitor of the Hedgehog pathway. It binds to and inhibits Smoothened (SMO), a transmembrane protein involved in Hedgehog signal transduction. By blocking SMO, vismodegib prevents the activation of Hedgehog target genes that regulate cell proliferation, survival, and differentiation. This pathway is pathologically activated in the vast majority of basal cell carcinomas, often via mutations in PTCH1 or SMO.
FDA Indications
- Treatment of adults with metastatic basal cell carcinoma
- Treatment of adults with locally advanced basal cell carcinoma that has recurred following surgery or who are not candidates for surgery or radiation
Common Side Effects
- Muscle spasms
- Alopecia
- Dysgeusia (taste disturbance)
- Weight loss
- Fatigue
- Nausea
- Diarrhea
- Decreased appetite
- Amenorrhea
Clinical Pearl
Muscle spasms and dysgeusia are the most common reasons for treatment discontinuation; consider "drug holidays" or magnesium supplementation to manage spasms. The dysgeusia often leads to significant weight loss, so nutritional monitoring is vital. Advise male patients to use condoms with female partners (even if they have had a vasectomy) for 3 months after the last dose due to presence in semen. Response rates in BCC are very high, but many patients struggle to stay on therapy long-term due…