Pharmacologic Treatment of Transplant Recipients Infected With SARS-CoV-2: Considerations Regarding Therapeutic Drug Monitoring and Drug–Drug Interactions

  • Laure Elens
    Louvain Drug Research Institute (LDRI), Integrated Pharmacometrics, Pharmacogenomics and Pharmacokinetics (PMGK), Université catholique de Louvain (UCLouvain), Brussels, Belgium;
  • Loralie J. Langman
    Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota;
  • Dennis A. Hesselink
    Division of Nephrology and Transplantation, Department of Internal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands;
  • Stein Bergan
    Department of Pharmacology, Oslo University Hospital, Oslo, Norway;
  • Dirk Jan A.R. Moes
    Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, the Netherlands;
  • Mariadelfina Molinaro
    Clinical and Experimental Pharmacokinetics Lab, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy;
  • Raman Venkataramanan
    School of Pharmacy and Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania;
  • Florian Lemaitre
    Univ Rennes, CHU Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail)—UMR_S 1085, Rennes, France; and

説明

<jats:sec> <jats:title>Background:</jats:title> <jats:p>COVID-19 is a novel infectious disease caused by the severe acute respiratory distress (SARS)-coronavirus-2 (SARS-CoV-2). Several therapeutic options are currently emerging but none with universal consensus or proven efficacy. Solid organ transplant recipients are perceived to be at increased risk of severe COVID-19 because of their immunosuppressed conditions due to chronic use of immunosuppressive drugs (ISDs). It is therefore likely that solid organ transplant recipients will be treated with these experimental antivirals.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>This article is not intended to provide a systematic literature review on investigational treatments tested against COVID-19; rather, the authors aim to provide recommendations for therapeutic drug monitoring of ISDs in transplant recipients infected with SARS-CoV-2 based on a review of existing data in the literature.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>Management of drug–drug interactions between investigational anti-SARS-CoV-2 drugs and immunosuppressants is a complex task for the clinician. Adequate immunosuppression is necessary to prevent graft rejection while, if critically ill, the patient may benefit from pharmacotherapeutic interventions directed at limiting SARS-CoV-2 viral replication. Maintaining ISD concentrations within the desired therapeutic range requires a highly individualized approach that is complicated by the pandemic context and lack of hindsight.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>With this article, the authors inform the clinician about the potential interactions of experimental COVID-19 treatments with ISDs used in transplantation. Recommendations regarding therapeutic drug monitoring and dose adjustments in the context of COVID-19 are provided.</jats:p> </jats:sec>

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