Elevated Tacrolimus Blood Concentration Due to the Interaction with Nirmatrelvir/Ritonavir During COVID-19 Treatment: A Case Report

Background. Nirmatrelvir/ritonavir, a newly authorized drug for the treatment of COVID-19, is a strong CYP3A4 inhibitor that can interact with many drugs, such as tacrolimus, reducing its metabolism. The reported case is a renal transplant patient who experienced a strong increase in tacrolimus blood concentration (up to 112ng/mL, more than ten times above the target range) when treated with both drugs at the same time, which caused a neurologic condition that required hospital admission for its control and treatment. The resolution of the symptoms was rapid, but the elevation of tacrolimus concentration remained for several days, even after discontinuing both drugs. This case shows the importance of developing a protocol for managing this interaction to guarantee the efficacy and safety of treatment with nirmatrelvir/ritonavir in transplant patients.