Background and Importance Nirmatrelvir/ritonavir (N/R) is an oral treatment for COVID-19 that reduces the risk of developing severe disease. Renal transplant patients are treated with immunosuppressants such as tacrolimus, that is metabolised by CYP43A as well as N/R. Co-administration with the irreversible CYP3A4 inhibitor ritonavir, is associated with serious interactions and toxicity in patients.

Aim and Objectives To describe the management of COVID-19 treatment with N/R and tacrolimus in renal transplant patients.

Material and Methods A 49-year-old woman with chronic kidney disease who underwent kidney transplantation in February 2019. She was on treatment with prednisone, mycophenolate and tacrolimus, presenting chronic rejection in April 2023 for which she received rituximab.

In June 2023 she was admitted to a tertiary hospital with a diagnosis of COVID-19 and severe pneumonia, requiring supplemental oxygen. She had received four doses of the COVID-19 vaccine and was on tacrolimus 5 mg/day, with a creatinine of 1.7 mg/dl. Due to the interaction of tacrolimus with N/R, she was first treated with remdesivir.

Results Due to the lack of clinical improvement, the Infectious Diseases, Nephrology, and Pharmacy units decided to initiate N/R adjusted to renal function (eGRF 30–60 ml/min) at a dosage of 150/100 mg/12 hours for 5 days. Tacrolimus was suspended during the treatment, with diligent therapeutic drug monitoring (TDM).

Tacrolimus concentration was measured prior to commencing N/R therapy. Because of the somewhat elevated tacrolimus concentration (16.4 ng/mL), it was determined to postpone the initiation of N/R for 48 hours. During N/R treatment, tacrolimus concentration remained around 6–7 ng/ml (target: 5–15 ng/ml). Four days after the end of N/R, the plasma level was 2.2 ng/mL, leading to the decision to reintroduce tacrolimus at a reduced daily dose of 2.5 mg.

The infectious condition was successfully resolved following N/R, without any transplant rejection. However, the patient experienced a slight deterioration of creatinine levels, which returned to baseline values after restarting tacrolimus.

Conclusion and Relevance Our experience contributes additional evidence indicating that this interaction should not be considered a contraindication for N/R treatment in COVID-19 pneumonia patients and can be effectively managed through TDM of tacrolimus. Nevertheless, further studies involving a larger patient population are necessary to establish more precise conclusions.

Conflict of Interest No conflict of interest.