Paxlovid-Induced Tacrolimus Toxicity in the Treatment of COVID-19: A Case Report

Michael, Stephanie; Heilbronner, Rachel; Lloyd, Christopher M; Levitin, Howard

doi:10.7759/cureus.35489

Cited by 4 publications

(2 citation statements)

References 9 publications

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“…Many immunocompromised patients were not given Paxlovid due to the fear of these interactions. For instance, cases of tacrolimus toxicity due the interaction with Paxlovid were reported in solid organ transplant recipients [23][24][25][26]. Paxlovid can also cause drug interactions with statins, azole antifungals, warfarin and direct-acting oral anticoagulants (DOACs), which are commonly prescribed to this vulnerable group of patients at increased risk of COVID-19 complications [27].…”

Section: Discussionmentioning

confidence: 99%

Paxlovid for Treating COVID-19 Patients: A Case-Control Study From Two Hospitals in the Eastern Province of Saudi Arabia

Alsaeed,

Alkhalaf,

Alomran

et al. 2023

Cureus

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Background Coronavirus disease 2019 (COVID-19) is an infectious disease that shortly progressed into an unprecedented pandemic spreading all over the world and causing millions of deaths. Many new COVID-19-specific therapies were suggested for the treatment of the patients at increased risk of progression to severe disease, especially those who were unvaccinated and those with a likely inadequate vaccine response. One of the preferred therapies in this setting is Paxlovid, a combination of the oral protease inhibitors nirmatrelvir and ritonavir. Paxlovid was authorized by the Saudi Ministry of Health for the treatment of mild to moderate COVID-19. This study aimed to report the effects of Paxlovid on the mortality of the COVID-19 patients at Dammam Medical Complex (DMC) and Qatif Complex Hospital (QCH), two hospitals in the Eastern Provence of Saudi Arabia, and compare the results with the international data. Methods The study was a retrospective study that included all the COVID-19 patients who were treated with Paxlovid at DMC and QCH between January and December 2022. Those patients were compared with control COVID-19 patients who did not receive Paxlovid. The patients were included irrespective of their COVID-19 vaccination status. All the patients were managed according to the Saudi Ministry of Health guidelines. They were followed up through the infectious disease virtual clinics and were monitored for ICU admissions and death of any cause for three months following their COVID-19 infections. Results A total of 92 COVID-19 patients were included. The patients consisted of 47 male and 45 female patients (51.09% and 48.91%, respectively). The mean ± standard deviation for the patients' age was 55.58±19.25 years. Twenty-eight patients were given Paxlovid (30.43%). Eighteen patients (19.57%) died. The use of Paxlovid was associated with lower ICU admissions (0.0% vs. 18.75%, P value <0.05) and with lower deaths (3.57% vs 26.56%, P value <0.05) but the Paxlovid group included less immunocompromised patients (7.14% vs. 60.94%, P value <0.001), cancer patients (0.0% vs. 42.19%, P value <0.001), and chronic kidney disease patients (7.14% vs. 29.69%, P value <0.05) than the control group. Conclusion This study suggests that Paxlovid is highly effective in reducing the risk of severe COVID-19 or mortality. However, larger studies with better qualities are needed for a full assessment of the role of Paxlovid in COVID-19 management in Saudi Arabia.

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Section: Discussionmentioning

confidence: 99%

Paxlovid for Treating COVID-19 Patients: A Case-Control Study From Two Hospitals in the Eastern Province of Saudi Arabia

Alsaeed,

Alkhalaf,

Alomran

et al. 2023

Cureus

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“…[Public] February 9, 2024 varying degrees of effectiveness, ranging from moderate to less effective and some of the reported compounds still display a degree of toxicity . [20][21][22] Thus, it is crucial to develop novel chemical series that not only demonstrate increased potency but also address previously identified issues of toxicity and resistance. With this goal in mind, we aimed to participate in the CACHE challenge #3, where we could leverage our medicinal and computational chemistry expertise along with the available molecular and structural data to identify novel Mac1 binders with enhanced potency.…”

Section: Introductionmentioning

confidence: 99%

The Third CACHE Challenge – Finding Ligands Targeting the Macrodomain of SARS-CoV-2 NSP3 Using AI-inspired and Knowledge-Based Approaches.

Kumar B.V.S,

Rostaing,

Burai-Patrascu

et al. 2024

Preprint

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The SARS-CoV-2 virus contains a host of nonstructural proteins (NSPs) that contribute to its structure and viral function. Among them is the nonstructural protein 3 (NSP3), which contains a macrodomain (Mac1) that interferes with antiviral adenosine diphosphate (ADP)-ribosylation signaling. Catalytic mutations in Mac1 render viruses nonpathogenic, making this enzyme a promising target for antiviral development. For this reason, the third CACHE challenge focused on identifying binders of the Mac1 domain of NSP3 for the development of novel antivirals against SARS-CoV-2. To this end, we used available structural data of the NSP3 Mac1 domain in complex with known fragment binders as starting points for ligand discovery; our efforts were primarily focused on sub-sites of the ADP binding site in the NSP3 macrodomain. Then, using Artificial intelligence (AI)-guided and knowledge-based fragment merging and expansion approaches, we generated novel molecules that would serve as templates to identify highly similar compounds in the Enamine REAL database that would be commercially available. Our design yielded a library of 12,800 molecules, which was docked with our program FITTED to a representative crystal structure of NSP3. We ranked the predicted binding poses based on docking score, followed by visual pose analysis of the best 200 compounds. We finally selected and proposed 150 compounds for testing, followed by further shortlisting to yield a final list of 107 molecules. 91 compounds were purchased from Enamine and are being tested at the Structural Genomics Consortium (SGC). Our approach and findings will further contribute to our open science efforts, and we aim to continue to engage the scientific community.

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Safety Profile of Paxlovid in the Treatment of COVID-19

Lv,

Gao,

Zeng

et al. 2024

CPD

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Background:: With the urgent and widespread application of Paxlovid, a novel antiviral drug for Coronavirus Disease 2019 (COVID-19) in clinical practice, concerns regarding its actual efficacy and safety have emerged. In order to provide more evidence to support its clinical application, we sought to perform a descriptive analysis of cases who experienced at least one Paxlovid-related adverse event (AEs) and reported to the FDA Adverse Event Reporting System (FAERS) in the post-marketing period. Methods:: Individual adverse event reports between January 1, 2022 and September 30, 2022, were downloaded from the FAERS website. We completed a descriptive study about the safety of Paxlovid in the treatment of COVID-19. Further, we also analyzed the onset time of Paxlovid-related AEs Results:: As of 30 September 2022, 16,529 de-duplicated cases were submitted to the FDA, and 5,860 (35.45%) were female. The average age was 58.38 years (S.D. 15.50). Most reports (12,390, 74.96%) were submitted by consumers and 1,436 (8.68%) concerned serious outcomes. The most frequently reported AEs were disease recurrence (7,724, 16.23%), dysgeusia (2,877, 6.05%), and diarrhoea (1,448, 3.04%). The median onset time of Paxlovid-related AEs was 8 days (interquartile range,1-10 days), and most of the cases (2,629, 19.12%) occurred on the day after Paxlovid initiation. Conclusion:: This study indicates that the most common AEs reported with Paxlovid in post-marketing experience are consistent with the safety assessment of antiviral drugs. Even without emerging apparent safety concerns, the incidence of serious outcomes was unexpectedly high, and a few cases of potential new AEs occurred.

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Paxlovid-Induced Tacrolimus Toxicity in the Treatment of COVID-19: A Case Report

Cited by 4 publications

References 9 publications

Paxlovid for Treating COVID-19 Patients: A Case-Control Study From Two Hospitals in the Eastern Province of Saudi Arabia

Paxlovid for Treating COVID-19 Patients: A Case-Control Study From Two Hospitals in the Eastern Province of Saudi Arabia

The Third CACHE Challenge – Finding Ligands Targeting the Macrodomain of SARS-CoV-2 NSP3 Using AI-inspired and Knowledge-Based Approaches.

Safety Profile of Paxlovid in the Treatment of COVID-19

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