The management of immunosuppressors in solid organ transplantation requires pharmacological therapeutic monitoring with regular adaptation of the dosage to the residual level. An obvious cause of these fluctuations is drug interactions, particularly for mTOR inhibitors and anti-calcineurin drugs, which are highly metabolized by cytochromes P450. A 72-year-old lung transplanted man, treated by tacrolimus and everolimus in the long term, had his residual immunosuppressor levels unbalanced by the introduction of sotorasib, which is used for metastatic pulmonary adenocarcinoma. This imbalance is explained by the fact that sotorasib is an inducer of CYP3A4 and an inhibitor of PGP, but the strength of the interaction has never been studied. This will have required a threefold increase in dosages and weekly monitoring before satisfactory residual levels were achieved.