palbociclib + itraconazole

Palbociclib is an oral small molecule inhibitor of cyclin-dependent kinase 4 and 6 (CDK4/6), developed by Pfizer for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer. It works by blocking cell cycle progression from G1 to S phase in cancer cells, thereby inhibiting cellular proliferation[2][5][6]. Itraconazole is a triazole antifungal agent that acts as a strong inhibitor of cytochrome P450 3A (CYP3A) enzymes. When coadministered, itraconazole significantly increases the plasma exposure of palbociclib due to inhibition of its metabolism via CYP3A[1][6]. This combination is not used therapeutically but represents a clinically significant drug-drug interaction.