Vismodegib

Vismodegib is an oral small-molecule antagonist of the hedgehog signaling pathway that targets the Smoothened (SMO) receptor. By inhibiting SMO, it blocks downstream GLI transcription and reduces tumor cell proliferation in hedgehog-driven cancers. It is primarily used in the treatment of advanced skin cancer and is studied in other hedgehog-driven conditions.

Medical use and indications

Vismodegib is approved for adults with metastatic basal cell carcinoma or locally advanced basal cell carcinoma that has recurred after or is not amenable to curative surgery or radiotherapy. It is intended for disease control in patients for whom standard curative options are not suitable.

Administration and dosing

The recommended dose is 150 mg taken orally once daily. Treatment is continued until disease progression or intolerable toxicity. The drug is metabolized in the liver, and potential interactions with other medications, especially those affecting hepatic enzymes, should be considered.

Safety, contraindications, and precautions

Vismodegib is teratogenic and can cause fetal harm; effective contraception should be used by women of childbearing potential during treatment and for a period after stopping the drug. Men and women should discuss reproductive planning with their clinician. Breastfeeding during treatment is not recommended.

Adverse effects and pharmacology

Common adverse effects include muscle spasms, hair loss (alopecia), dysgeusia (taste disturbance), weight loss, fatigue, nausea, diarrhea, and decreased appetite. The drug is highly protein-bound and undergoes hepatic metabolism, with elimination occurring primarily via the liver and excretion in urine and feces.

History and status

Vismodegib (brand name Erivedge) received regulatory approval in 2012 for advanced basal cell carcinoma. It is part of the class of hedgehog pathway inhibitors, with other agents available for different indications and patients.