Neriman Sila Koç, Mehmet Deniz Ayli
Experimental and Clinical Transplantation - 2025;23(11):748-751
Sotorasib is a targeted therapy approved for the treatment of KRAS G12C-mutated non-small cell lung cancer and is known to induce cytochrome P450 3A4 and potentially modulate P-glycoprotein activity. Tacrolimus and everolimus, essential components of maintenance immunosuppression in kidney transplant recipients, depend on these pathways for metabolism. Although a significant interaction between soto rasib and these agents has been suggested in lung transplantation, such an interaction has not previously been described in kidney transplant recipients. We present a case of a kidney transplant recipient who experienced marked reductions in tacrolimus and everolimus trough concentrations shortly after initiation of sotorasib therapy. The temporal association, exclusion of alternative explanations, and known pharmacologic properties of sotorasib support a probable drug-drug interaction. This observation highlights an important and previously unreported risk for transplant recipients receiving sotorasib. Because calcineurin inhibitors and mechanistic target of rapamycin inhibitors have narrow therapeutic windows, even modest reductions in exposure may predispose to acute rejection. Transplant clinicians should closely monitor drug levels and coordinate care with oncology teams when initiating sotorasib to maintain adequate immunosuppression and protect graft function.
