ABSTRACT
Introduction: Paxlovid (nirmatrelvir+ ritonavir) is a promising new combination drug that can significantly reduce hospitalization and all-cause mortality in Covid-19 infection. Ritonavir is a potent inhibitor of cytochrome-P450 system CYP3A enzymes and concomitant use with calcineurin inhibitors (CNI) such as tacrolimus can dangerously increase CNI blood levels. We present a heart transplant recipient on tacrolimus who developed acute kidney injury (AKI) and refractory life-threatening hyperkalemia following Paxlovid use and successful treatment using P450 induction with phenytoin along with dialysis support. Case Description: A 43-year-old male with CKD stage III and previous heart transplant on tacrolimus was admitted with dyspnea, malaise, and oliguria. Few days earlier, he developed Covid-19 infection and received 5-day course of Paxlovid prescribed from elsewhere. On presentation, patient was hypervolemic, with the following serum values: K+ 7.1 mMol/L (peaking to 8.3 despite medical therapy), HCO3-17 mMol/L and creatinine 4.67 mg/dL (baseline 3.0). Patient required emergent hemodialysis. Tacrolimus trough level came back as >60 ng/mL Patient was started on IV phenytoin 100 mg every 12 hours. Tacrolimus levels remained extremely high over next few days with subsequent improvement (fig.). Patient required 4 dialysis sessions. Subsequently urine output improved, and serum creatinine returned to baseline. Discussion(s): Paxlovid use will likely increase with Covid-19 surge. This drug has important safety risks in organ transplant recipients and kidney disease as highlighted by our case, where supratherapeutic tacrolimus levels due to P450 inhibition resulted in AKI and hyperkalemia. Empiric dose reduction or withholding CNI agents when initiating Paxlovid with close CNI level monitoring is recommended. Risk mitigation strategies are also important such as interruptive alerts in electronic health records, educational outreach, and alerting pharmacies about Paxlovid-CNI interactions.
ABSTRACT
BACKGROUND AND PURPOSE: The recent SARS-CoV-2 pandemic has posed multiple challenges to the practice of clinical neurology including recognition of emerging neurological complications and management of coexistent neurological diseases. In a fast-evolving pandemic, evidence-based studies are lacking in many areas. This paper presents European Academy of Neurology (EAN) expert consensus statements to guide neurologists caring for patients with COVID-19. METHODS: A refined Delphi methodology was applied. In round 1, statements were provided by EAN scientific panels (SPs). In round 2, these statements were circulated to SP members not involved in writing them, asking for agreement/disagreement. Items with agreement >70% were retained for round 3, in which SP co-chairs rated importance on a five-point Likert scale. Results were graded by importance and reported as consensus statements. RESULTS: In round one, 70 statements were provided by 23 SPs. In round two, 259/1061 SP member responses were received. Fifty-nine statements obtained >70% agreement and were retained. In round three, responses were received from 55 co-chairs of 29 SPs. Whilst general recommendations related to prevention of COVID-19 transmission had high levels of agreement and importance, opinion was more varied concerning statements related to therapy. CONCLUSION: This is the first structured consensus statement on good clinical practice in patients with neurological disease during the COVID-19 pandemic that provides immediate guidance for neurologists. In this fast-evolving pandemic, a rapid response using refined Delphi methodology is possible, but guidance may be subject to change as further evidence emerges.