Sonidegib

Hedgehog inhibition in skeletal muscle causes myalgia and, more than with vismodegib, biochemical muscle injury with rising creatine kinase. In the uncommon event of frank rhabdomyolysis, released myoglobin is freely filtered and precipitates with Tamm-Horsfall protein in the distal/proximal tubule, causing direct heme-pigment tubular toxicity, intratubular cast obstruction and renal vasoconstriction — i.e. pigment (myoglobinuric) ATN. Volume depletion amplifies cast formation and ischemic injury.

Muscle aches and weakness with elevated CK; in severe cases dark (tea-colored) urine, dipstick blood without red cells on microscopy (myoglobinuria), rising creatinine and a muddy-brown-cast ATN picture, often with hyperkalemia and hyperphosphatemia. Most CK rises are asymptomatic and isolated.

CK elevations during the first weeks-to-months of therapy; rhabdomyolysis-driven AKI would follow a significant muscle-injury event.

Oral selective inhibitor of Smoothened (SMO) in the Hedgehog pathway, used for locally advanced basal cell carcinoma. Like vismodegib it shuts down constitutive Hedgehog signaling driven by PTCH1 loss or SMO mutation.

For rhabdomyolysis: stop sonidegib, give aggressive isotonic IV fluids to maintain brisk urine output, correct electrolytes (hyperkalemia, hyperphosphatemia), and support kidney function — dialysis if refractory hyperkalemia, acidosis or volume overload. Isolated asymptomatic CK elevation is monitored with dose interruption per thresholds. Renal recovery is common with prompt volume resuscitation.