Objectives Nirmatrelvir/ritonavir may cause a clinically relevant drug-drug interaction (DDI) with immunosuppressive drugs, such as tacrolimus, which may condition the use of this antiviral in transplant patients. We aimed to describe the management of this interaction. Methods Descriptive study in which renal transplant patients in treatment with nirmatrelvir/ritonavir and tacrolimus were included. They suspended tacrolimus the day before starting the antiviral treatment, and the decision to restart it was made based on their tacrolimus blood levels. Main variables studied to measure this DDI were tacrolimus blood concentration, dose adjustment and serum creatinine. Results Three patients were included. During the study, tacrolimus levels elevation did not have repercussion in the serum creatinine, that remained stable in all patients. No patient required hospitalisation or showed signs of rejection.Conclusions Our experience provides further evidence that this interaction should not be a contraindication to treatment with nirmatrelvir/ritonavir, and can be managed with close monitoring of tacrolimus levels.

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Nirmatrelvir/ritonavir, a newly authorized drug for the treatment of COVID-19, is a strong CYP3A4 inhibitor, which can interact with a large number of 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 the reference range) when treated with both drugs at the same time, which caused a neurological condition that required hospital admission its control and treatment. The resolution of the symptoms was rapid, but the elevation of tacrolimus concentration remained for several days, even after discontinuation of both drugs. This study shows the importance of developing a protocol for the management of this interaction to guarantee the efficacy and safety of treatment with nirmatrelvir/ritonavir in transplant patients.