Effect of nirmatrelvir/ritonavir on calcineurin inhibitor levels: Early experience in four SARS-CoV-2 infected kidney transplant recipients

Wang, Aileen X.; Koff, Alan; Hao, Diana; Tuznik, Natascha M.; Huang, Yuning

doi:10.1111/ajt.16997

Cited by 32 publications

(30 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 9 Although the previously published NYPH protocol can effectively help manage the ritonavir‐related drug interactions, this protocol requires intensive therapeutic drug monitoring and should not be followed if drug levels cannot be adequately measured over time. 6 , 17 Additionally, NR is not recommended for patients with an eGFR <30 ml/min, and as such renal transplant recipients or other SOTR with chronic kidney disease may be excluded from this treatment option. Treatment with both sotrovimab and NR should be initiated as soon as possible after confirmation of COVID‐19; the FDA emergency use authorization (EUA) criteria for NR specifies that treatment should begin within 5 days of symptom onset, whereas the sotrovimab EUA (prior to its authorization being revoked in the United States) specified first that treatment should occur within 10 days of symptom onset before it was later revised to 7 days.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 therapeutics and outcomes among solid organ transplant recipients during the Omicron BA.1 era

Hedvat

Lange

Salerno

et al. 2022

American Journal of Transplantation

View full text Add to dashboard Cite

Treatment outcomes associated with the use of novel COVID‐19 therapeutics in solid organ transplant recipients (SOTR) are not well described in the literature. The objective of this analysis was to characterize 30‐day hospitalization and other key secondary endpoints experienced by outpatient SOTR with mild–moderate COVID‐19 treated with nirmatrelvir/ritonavir (NR), sotrovimab, or no SARS‐CoV‐2 specific treatment. This IRB‐approved, retrospective study included 154 SOTR with a documented positive SARS‐CoV‐2 infection between December 16, 2021 and January 19, 2022 (a predominant Omicron BA.1 period in New York City). Patients who received NR ( N = 28) or sotrovimab ( N = 51) experienced a lower rate of 30‐day hospitalization or death as compared to those who received no specific treatment ( N = 75) ( p = .009). A total of three deaths occurred, all among patients who initially received no specific treatment prior to hospitalization. These results suggest a role for SARS‐CoV‐2 specific agents in the treatment of SOTR with COVID‐19, and that there does not appear to be any difference in effectiveness when comparing NR versus sotrovimab.

show abstract

Section: Discussionmentioning

confidence: 99%

COVID-19 therapeutics and outcomes among solid organ transplant recipients during the Omicron BA.1 era

Hedvat

Lange

Salerno

et al. 2022

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

“…One patient had a tacrolimus trough level of 24.6 ng/mL on day 10 after resuming their usual dose on day 7. The authors concluded that “the clinically significant interaction between NR and immunosuppressive agents can be reasonably managed with a standardized dosing protocol.” 67 Supporting this, Wang et al 68 reported on 4 kidney transplant recipients treated with nirmatrelvir/ritonavir using a similar regimen of holding tacrolimus, checking tacrolimus levels on days 2 and 3 and again after completion. Days 2 and 3 tacrolimus levels were close to baseline and then declined to near 0 by days 8 and 9.…”

Section: Oral Therapies For Covid-19: Nirmeltravir/ritonavir and Moln...mentioning

confidence: 90%

“…Days 2 and 3 tacrolimus levels were close to baseline and then declined to near 0 by days 8 and 9. 68 Despite these reports of manageable tacrolimus levels, it is still advisable to proceed with caution given the potential for toxicity, especially if close laboratory monitoring cannot be accomplished, and given that other options for early therapy are available. Further recommendations are discussed in the American Society of Transplantation’s statement on oral antiviral therapy for COVID.…”

Section: Oral Therapies For Covid-19: Nirmeltravir/ritonavir and Moln...mentioning

confidence: 99%

Update on COVID-19 Therapeutics for Solid Organ Transplant Recipients, Including the Omicron Surge

Avery

2022

Transplantation

View full text Add to dashboard Cite

Major changes have occurred in therapeutics for coronavirus-19 (COVID-19) infection over the past 12–18 mo, most notably in early outpatient therapy. In most cases, solid organ transplant recipients were not included in the original clinical trials of these agents, so studies of real-world outcomes have been important in building our understanding of their utility. This review examines what is known about clinical outcomes in solid organ transplant recipients with newer therapies. SARS-CoV-2 monoclonal antibodies for early treatment or prophylaxis have likely prevented many hospitalizations and deaths. In addition, convalescent plasma, the oral drugs nirmatrelvir/ritonavir and molnupiravir, remdesivir for early outpatient treatment, anti-inflammatory therapy, and investigational virus-specific T-cell therapy will be discussed. Finally, the later consequences of COVID-19, such as secondary infections, long COVID symptoms, and persistent active infection, are identified as areas for future research.

show abstract

“…If TDM is available, early experience in four SARS‐CoV‐2–infected kidney transplant recipients on tacrolimus supports holding the immunosuppressant on the day of nirmatrelvir/ritonavir initiation and to monitor closely drug levels to guide the reintroduction of tacrolimus. 13 , 53 …”

Section: Potential Ddis Between Nirmatrelvir/ritonavir and Comedicati...mentioning

confidence: 99%

Recommendations for the Management of Drug–Drug Interactions Between the COVID‐19 Antiviral Nirmatrelvir/Ritonavir (Paxlovid) and Comedications

Marzolini

Kuritzkes

Marra

et al. 2022

Clin Pharma and Therapeutics

144

112

View full text Add to dashboard Cite

The coronavirus disease 2019 (COVID‐19) antiviral nirmatrelvir/ritonavir (Paxlovid) has been granted authorization or approval in several countries for the treatment of patients with mild to moderate COVID‐19 at high risk of progression to severe disease and with no requirement for supplemental oxygen. Nirmatrelvir/ritonavir will be primarily administered outside the hospital setting as a 5‐day course oral treatment. The ritonavir component boosts plasma concentrations of nirmatrelvir through the potent and rapid inhibition of the key drug‐metabolizing enzyme cytochrome P450 (CYP) 3A4. Thus nirmatrelvir/ritonavir, even given as a short treatment course, has a high potential to cause harm from drug–drug interactions (DDIs) with other drugs metabolized through this pathway. Options for mitigating risk from DDIs with nirmatrelvir/ritonavir are limited due to the clinical illness, the short window for intervention, and the related difficulty of implementing clinical monitoring or dosage adjustment of the comedication. Pragmatic options are largely confined to preemptive or symptom‐driven pausing of the comedication or managing any additional risk through counseling. This review summarizes the effects of ritonavir on drug disposition (i.e., metabolizing enzymes and transporters) and discusses factors determining the likelihood of having a clinically significant DDI. Furthermore, it provides a comprehensive list of comedications likely to be used in COVID‐19 patients which are categorized according to their potential DDI risk with nirmatrelvir/ritonavir. It also discusses recommendations for the management of DDIs which balance the risk of harm from DDIs with a short course of ritonavir, against unnecessary denial of nirmatrelvir/ritonavir treatment.

show abstract

Effect of nirmatrelvir/ritonavir on calcineurin inhibitor levels: Early experience in four SARS-CoV-2 infected kidney transplant recipients

Cited by 32 publications

References 1 publication

COVID-19 therapeutics and outcomes among solid organ transplant recipients during the Omicron BA.1 era

COVID-19 therapeutics and outcomes among solid organ transplant recipients during the Omicron BA.1 era

Update on COVID-19 Therapeutics for Solid Organ Transplant Recipients, Including the Omicron Surge

Recommendations for the Management of Drug–Drug Interactions Between the COVID‐19 Antiviral Nirmatrelvir/Ritonavir (Paxlovid) and Comedications

Contact Info

Product

Resources

About