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

被引:49
作者
Elens, Laure [1 ,2 ]
Langman, Loralie J. [3 ]
Hesselink, Dennis A. [4 ,5 ]
Bergan, Stein [6 ]
Moes, Dirk Jan A. R. [7 ]
Molinaro, Mariadelfina [8 ]
Venkataramanan, Raman [9 ]
Lemaitre, Florian [10 ,11 ]
机构
[1] Univ Catholique Louvain UCLouvain, Louvain Drug Res Inst LDRI, Integrated Pharmacometr Pharmacogen & Pharmacokin, Ave Emmanuelle Mounier 72 B01-02, B-1200 Brussels, Belgium
[2] Univ Catholique Louvain UCLouvain, Louvain Ctr Toxicol & Appl Pharmacol LTAP, Inst Rech Expt & Clin IREC, Brussels, Belgium
[3] Mayo Clin, Dept Lab Med & Pathol, Coll Med, Rochester, MN USA
[4] Univ Med Ctr Rotterdam, Dept Internal Med, Div Nephrol & Transplantat, Erasmus MC, Rotterdam, Netherlands
[5] Oslo Univ Hosp, Rotterdam Transplant Grp, Oslo, Norway
[6] Oslo Univ Hosp, Dept Pharmacol, Oslo, Norway
[7] Leiden Univ, Dept Clin Pharm & Toxicol, Med Ctr, Leiden, Netherlands
[8] Fdn IRCCS Policlin San Matteo, Clin & Expt Pharmacokinet Lab, Pavia, Italy
[9] Univ Pittsburgh, Sch Pharm & Med, Pittsburgh, PA USA
[10] Univ Rennes, Irset Inst Rech Sante Environm & Travail UMR S 10, EHESP, CHU Rennes,INSERM, Rennes, France
[11] INSERM, Ctr Invest Clin, CIC 1414, Rennes, France
关键词
COVID-19; SARS-CoV-2; drug interactions; transplant patients; therapeutic drug monitoring; experimental treatments; calcineurin inhibitors; mammalian target of rapamycin inhibitors; mycophenolic acid; tacrolimus; cyclosporin; sirolimus; everolimus; recommendations; immunocompromised; hydroxychloroquine; chloroquine; remdesivir; protease inhibitors; lopinavir; tocilizumab; BAYESIAN-ESTIMATION; CYCLOSPORINE PHARMACOKINETICS; POPULATION PHARMACOKINETICS; CLINICAL PHARMACOKINETICS; DOSING MODIFICATIONS; PROTEASE INHIBITOR; MYCOPHENOLIC-ACID; SARS CORONAVIRUS; KIDNEY; LIVER;
D O I
10.1097/FTD.0000000000000761
中图分类号
R446 [实验室诊断]; R-33 [实验医学、医学实验];
学科分类号
1001 ;
摘要
Background: 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. Methods: 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. Results: 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. Conclusions: 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.
引用
收藏
页码:360 / 368
页数:9
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