Vismodegib

The dominant toxicity is muscle spasm (myalgia) from Hedgehog inhibition in muscle, occasionally with creatine kinase elevation. The renal-relevant signal is an electrolyte one: hyponatremia, in some reports of an SIADH pattern (euvolemic, inappropriately concentrated urine, low serum osmolality), reflecting disordered free-water handling at the collecting duct rather than tubular toxicity. Volume loss from vomiting/diarrhea or poor intake can additionally contribute to hyponatremia and prerenal physiology.

Painful muscle cramps, dysgeusia/ageusia, alopecia and weight loss are the hallmark adverse events. When hyponatremia occurs it is usually mild and asymptomatic but can present with nausea, lethargy or confusion; labs show low serum sodium and osmolality with inappropriately concentrated urine when SIADH-type.

Muscle spasms within the first weeks-to-months; hyponatremia is sporadic and variable in timing.

Oral small-molecule inhibitor of Smoothened (SMO), a transmembrane component of the Hedgehog signaling pathway. In basal cell carcinoma, constitutive Hedgehog activation (PTCH1 loss or SMO mutation) drives tumor growth; vismodegib blocks SMO to shut down the pathway.

Manage muscle spasms supportively (hydration, dose interruptions; some use calcium-channel blockers or L-carnitine empirically). For hyponatremia, determine volume status: fluid-restrict and treat the underlying SIADH-type physiology if euvolemic, or rehydrate if hypovolemic; correct sodium at a safe rate. Dose-interrupt for intolerable spasms. Most electrolyte effects reverse with management.