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Backround Tacrolimus toxicity in patients status post orthotropic heart transplantation is not commonly reported. Given its narrow therapeutic window and drug-drug interactions, it must be closely monitored by providers experienced in transplant management. There are no case series of patients with tacrolimus toxicity in the setting of treatment for Sars-2-CoV-19 (COVID 19) for heart transplant recipients. We present a case of tacrolimus toxicity in the setting of concurrent ritonavir-nirmatrelvir (Paxlovid) use. Case Summary The patient was a 74-year-old male with a prior significant history of heart transplantation and on maintenance immunosuppression with tacrolimus. He contracted COVID-19 and was prescribed antiviral therapy with Paxlovid by an outside provider prior to admission. The patient complained of severe headaches, dehydration, and tremors. After eliminating acute intracranial processes with imaging, laboratory investigation revealed a severely elevated tacrolimus level with acute renal injury. The patient was taken on this medicine and treated conservatively with intravenous hydration. The symptoms improved, particularly the headaches. He was discharged with instructions to resume his home dosing of tacrolimus and return to clinic in 1 week with a repeat trough level. The subsequent trough level was no longer supra-therapeutic.

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