Acute kidney injury and tacrolimus toxicity in a kidney transplant recipient treated with nirmaltrevir/ritonavir: a case report

Background Kidney transplant recipients with severe acute respiratory syndrome-coronavirus-2 infection have an increased risk of severe disease and mortality. Nirmaltrevir/ritonavir (Paxlovid) is an effective oral disease-modifying therapy that has been shown to reduce risk of progression to severe disease in high-risk, nonhospitalized adults. However, owing to the potential for serious drug-drug interactions owing to ritonavir-induced inhibition of the CYP3A enzyme, this drug is not suitable option for transplant recipients with mild-moderate severe acute respiratory syndrome-coronavirus-2 infection. Case presentation A 57-year-old Caucasian man presented to the emergency department with 48 hours of nausea, vomiting, headaches, and lethargy. At 5 days earlier, he was diagnosed with a mild severe acute respiratory syndrome-coronavirus-2 infection by his general practitioner, who commenced treatment with Paxlovid at 300 mg/100 mg twice daily. Past medical history included kidney transplantation in 2018 for end-stage kidney secondary to hypertensive nephrosclerosis, managed with prednisone, tacrolimus, and mycophenolate. Vaccination status was up-to-date and prophylactic tixagevimab/cilgavimab (Evusheld) had been given > 6 months prior owing to lack of seroconversion. Examination showed a blood pressure of 176/94 mmHg and normal respiratory parameters. Investigations demonstrated a serum creatinine of 213 mu mol/L (baseline 130 mu mol/L) and tacrolimus trough level of 118 mu g/L (baseline 6.9-8.7 mu g/L). Treatment included intravenous rehydration, Evusheld and tacrolimus were withheld for 7 days, with recommencement guided by regular therapeutic drug monitoring. Conclusion This acute kidney injury was attributed to tacrolimus toxicity resulting from a drug-drug interaction with Paxlovid. While transplant recipients have an increased risk of severe disease, current Australian guidelines recommend against Paxlovid use in adults taking medications that are heavily dependent on CYP3A4 for clearance, including calcineurin and mammalian target of rapamycin inhibitors.