March 2025

Hello Doctor,

Below is in response to the inquiry: A 43 year old male solid organ kidney post-transplant patient who is on Prograf 8mg PO every 12 hours, came into the clinic 8 months post transplant with extreme drowsiness, confusion, nausea, and elevated renal and liver function markers such as creatinine, blood urea nitrogen, and liver enzymes.The patient is on Vitamin B12 (past 8 months) and Folic Acid (past 8 months) which was prescribed as a supplement post renal transplant by our team. The patient also indicated that Paxlovid Standard Dose Pack 300mg :100mg (past 4 days) was initiated by an outside provider of the hospital, her PCP. The patient weight is 80kg with a GFR of 80mL/min. Can you tell me what is going on with this patient and if I can continue all his medications or if any adjustments need to be made based on his symptoms, lab values, and drug therapy he is on?

Patients who are Immunocompromised, such as those receiving solid organ transplant, are ideal candidates for treatment with antiviral medications. In this case, Paxlovid, was recommended to be taken by an outside provider of the hospital, her PCP. Paxlovid is an antiviral medication that contains nirmatrevir and ritonavir as ingredients used in the treatment of COVID-19. However, Ritonavir is considered a CYP3A4 inhibitor which can impact the effectiveness of the patient’s Prograf (tacrolimus) due to its metabolism being guided by CYP3A4. Paxlovid and tacrolimus can interact with one another leading to a potential significant increase in body tacrolimus levels.

Based on the patients’ current symptoms along with elevated liver enzymes, serum creatinine, and blood urea nitrogen levels, the patient can be experiencing problems related to elevated levels of tacrolimus. In a case report done in August of 2022, a kidney transplant patient took Paxlovid while resuming their normal immunosuppressant maintenance therapy including Tacrolimus, mycophenolate, and prednisone. However, while taking the Paxlovid, the patient experienced symptoms such as nausea and vomiting by day 2 and his tacrolimus levels were elevated, leading to the Paxlovid to be discontinued by day 3. Acutely high tacrolimus levels can lead to elevated creatinine levels and an acute kidney injury.

In this patient’s presentation the patient looks to be experiencing toxicity due to the increase in tacrolimus levels due to the Paxlovids impact. It is recommended that due to the severity of the symptoms and the increase in serum creatinine and liver enzymes, the Paxlovid should be discontinued to prevent worsening of the patients symptoms due to toxicity and injury to the kidney and or liver. For this patient with a GFR of 80 mL/min, the Paxlovid dose required no dose adjustment. If possible, the tacrolimus should have been held for 2-3 days while taking Paxlovid. The dose of prograf should also have been reduced to prevent acute increases in the levels while the patient took Paxlovid. Since the patient is experiencing symptoms of toxicity, the prograf and Paxlovid should be discontinued until the patient's symptoms are resolved and the levels of the tacrolimus and serum creatinine should be monitored until they return within normal limits. Once the tacrolimus levels are within normal therapeutic limits, the prograf therapy should be restarted.

Reference: 

Prikis, M., & Cameron, A. (2022). Paxlovid (nirmatelvir/ritonavir) and Tacrolimus Drug-drug interaction in a kidney transplant patient with Sars-2-cov infection: A case report. Transplantation Proceedings, 54(6), 1557–1560. https://doi.org/10.1016/j.transproceed.2022.04.015