Supratherapeutic Tacrolimus Concentrations With Nirmatrelvir/Ritonavir in Solid Organ Transplant Recipients Requiring Hospitalization: A Case Series Using Rifampin for Reversal

Rose, Dusten T.; Gandhi, Sanyam; Bedard, Rachael A.; Mondy, Kristin; Chu, Alexander L.; Gamble, Kelly C.; Gee, Amanda T.; Kundra, Monica A.; Williams, Amber; Lee, Brian K.

doi:10.1093/ofid/ofac238

Cited by 23 publications

(21 citation statements)

References 12 publications

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“…Case reports among immunocompromised hosts, including among PLWH, have discussed long durations of persistence of viral antigen and culturable virus in the context of persistent or recurrent symptoms, with antiviral treatment courses repeated [71][72][73]. Additional research will need to explore the relationship between immunocompromise and antiviral resistance [73], need for antiviral retreatment [71], and potential for drug interactions with other essential therapies [74].…”

Section: Protection From Sars-cov-2 Vaccinationmentioning

confidence: 99%

COVID-19 Outcomes and Risk Factors Among People Living with HIV

2022

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Purpose of Review In this review, we examine the intersection of the HIV and COVID-19 epidemics with focus on COVID-19-related health outcomes and risk factors for SARS-CoV-2 among people living with HIV (PLWH). Recent Findings Evidence to date do not suggest a higher incidence of SARS-CoV-2 infection among PLWH compared to the general population, although—once exposed—PLWH are at greater risk of severe COVID-19 outcomes. Key risk factors for severe COVID-19 include non-HIV comorbidities known to be associated with severe disease, as well as HIV-specific risk factors such as low CD4 + T-cell count, unsuppressed viral load, and tuberculosis co-infection. The disproportionate impact of the SARS-CoV-2 pandemic among Black, Latinx, and Native American/Alaskan Native PLWH could worsen pre-existing disparities in health outcomes among PLWH. Data on SARS-CoV-2 vaccine protection among PLWH needs additional study, although some studies suggest decreased humoral responses among those with low CD4 + T-cell counts, while there is a signal of increased vaccine breakthrough rates among PLWH in two large observational cohorts. Data on post-acute sequelae of SARS-CoV-2 (PASC) among PLWH is also limited. Summary PLWH do not have a higher susceptibility to SARS-CoV-2, but once exposed, they are at higher risk of severe COVID-19 outcomes. Additional resources will need to be dedicated to the development of interventions to improve health outcomes and address disparities among PLWH impacted by the COVID-19 pandemic.

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Section: Protection From Sars-cov-2 Vaccinationmentioning

confidence: 99%

COVID-19 Outcomes and Risk Factors Among People Living with HIV

2022

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“…The median time for the tacrolimus concentration to return to baseline levels after holding NR was 8 (IQR, 7–12) days. Notably, in two case reports ( 20 , 21 ), rifampin and phenytoin were used to accelerate tacrolimus metabolism, resulting in a rapid decline in therapeutic levels.…”

Section: Resultsmentioning

confidence: 99%

“…( 18 ) doubled the prednisone dose while maintaining mycophenolic acid; and Rose et al. ( 20 ) also maintained mycophenolic acid. There was no report on the effect of this adjustment.…”

Section: Resultsmentioning

confidence: 99%

Optimizing the use of nirmatrelvir/ritonavir in solid organ transplant recipients with COVID-19: A review of immunosuppressant adjustment strategies

Tang

Song

2023

Front. Immunol.

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The coronavirus disease 2019 (COVID-19) pandemic has caused a significant burden of morbidity and mortality worldwide, with solid organ transplant recipients (SOTRs) being particularly vulnerable. Nirmatrelvir and ritonavir have demonstrated the potential for reducing the risk of hospitalization and death in patients with mild-to-moderate COVID-19. However, ritonavir has a strong drug–drug interaction with CYP3A-dependent drugs such as calcineurin inhibitors, potentially leading to rapid increases in blood concentration. As SOTRs are commonly prescribed immunosuppressants, co-administration with nirmatrelvir/ritonavir requires careful consideration. To address this issue, we conducted a literature review to evaluate the use and adverse effects of nirmatrelvir/ritonavir in SOTRs and explore feasible immunosuppressant adjustment regimens. Our findings suggest that nirmatrelvir/ritonavir could be a feasible treatment option for COVID-19 in SOTRs, provided that appropriate immunosuppressive drug management is in place during co-administration. Although prescribing the novel anti-SARS-CoV-2 drug to transplant recipients poses challenges, potential strategies to overcome these issues are discussed. Further studies are needed to determine the optimal dosing strategies of nirmatrelvir/ritonavir, immunosuppressant adjustment, and monitoring in this patient population.

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“…While this could be favorable for therapeutic use in the management of viral infections such as COVID-19, the effect on P450 is potentially problematic in patients who are also prescribed a broad range of medications that utilize this enzymatic process. This wide variety of medications includes some anticoagulants, anticonvulsants, corticosteroids, pethidine, amiodarone, flecinide, colchicine, clozapine, lovastatin, simvastatin, sildenafil, midazolam and certain immunosuppressants [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

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

Michael¹,

Heilbronner²,

Lloyd³

et al. 2023

Cureus

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Paxlovid TM (nirmaltrelvir/ritonavir) received emergency use authorization from the Food and Drug Administration (FDA) in December 2021 to treat coronavirus disease 2019 . Given the actions of Paxlovid on cytochrome P450-3A4 (CYP3A4) enzymes, it is imperative to check for potential drug-drug interactions before prescribing. We describe a case in which the common emergency department presentation of generalized weakness was found to be caused by interactions between Paxlovid and a patient's home medications resulting in tacrolimus toxicity.

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Supratherapeutic Tacrolimus Concentrations With Nirmatrelvir/Ritonavir in Solid Organ Transplant Recipients Requiring Hospitalization: A Case Series Using Rifampin for Reversal

Cited by 23 publications

References 12 publications

COVID-19 Outcomes and Risk Factors Among People Living with HIV

COVID-19 Outcomes and Risk Factors Among People Living with HIV

Optimizing the use of nirmatrelvir/ritonavir in solid organ transplant recipients with COVID-19: A review of immunosuppressant adjustment strategies

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

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