Sonidegib — Drug Monograph
Brand names: Odomzo
Drug class: Other
Mechanism of Action
Sonidegib is an inhibitor of the Hedgehog signaling pathway. It binds to and inhibits Smoothened (SMO), a G protein-coupled receptor-like protein that positively regulates the Hedgehog pathway. Inhibition of SMO prevents the nuclear translocation and activation of GLI transcription factors, thereby inhibiting the expression of genes involved in cell proliferation, differentiation, and survival. This suppresses the growth of tumor cells with an overactive Hedgehog pathway.
FDA Indications
- Treatment of adult patients with locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy
Common Side Effects
- Muscle spasms
- Alopecia
- Dysgeusia
- Fatigue
- Nausea
- Diarrhea
- Weight loss
- Decreased appetite
- Myalgia
- Abdominal pain
Clinical Pearl
Unlike vismodegib, sonidegib specifically requires monitoring of serum creatine kinase (CK) due to the risk of musculoskeletal toxicity and rare rhabdomyolysis. Sonidegib has a very long half-life (~28 days), meaning side effects may take a long time to resolve after stopping the drug. It is only approved for locally advanced BCC, whereas vismodegib is also approved for metastatic disease. Ensure the patient understands the strict empty-stomach requirement to avoid unpredictable spikes in drug…