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

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

Publication date: Dec 20, 2024

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. 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 umol/L (baseline 130 umol/L) and tacrolimus trough level of 118 ug/L (baseline 6. 9-8. 7 ug/L). Treatment included intravenous rehydration, Evusheld and tacrolimus were withheld for 7 days, with recommencement guided by regular therapeutic drug monitoring. 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.

Concepts Keywords
Australian Acute Kidney Injury
Coronavirus AKI
Daily Antiviral Agents
Headaches Antiviral Agents
Kidney Case report
COVID-19
COVID-19
COVID-19 Drug Treatment
Drug Interactions
Humans
Immunosuppressive Agents
Immunosuppressive Agents
Kidney transplant
Kidney Transplantation
Male
Middle Aged
Paxlovid
Ritonavir
Ritonavir
SARS-CoV-2
Tacrolimus
Tacrolimus

Semantics

Type Source Name
disease MESH Acute kidney injury
drug DRUGBANK Tacrolimus
drug DRUGBANK Ritonavir
disease MESH severe acute respiratory syndrome
disease MESH infection
disease MESH drug interactions
disease MESH emergency
disease IDO history
disease MESH nephrosclerosis
drug DRUGBANK Prednisone
drug DRUGBANK Mycophenolic acid
disease MESH seroconversion
disease IDO blood
drug DRUGBANK Creatinine
disease MESH COVID-19

Original Article

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