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Title: High rate of major drug-drug interactions of lopinavir-ritonavir for COVID-19 treatment
Authors: Macías, Juan
Pinilla, Ana
Lao-Dominguez, Francisco A.
Corma, Anaïs
Contreras-Macias, Enrique
González-Serna, Alejandro
Gutierrez-Pizarraya, Antonio
Fernández-Fuertes, Marta
Morillo-Verdugo, Ramón
Trigo, Marta
Real, Luis M.
Pineda, Juan A.
metadata.dc.contributor.authoraffiliation: [Macías,J; Pinilla,A; Corma,A; González-Serna,A; Fernández-Fuertes,M; Trigo,M; Real,LM; Pineda,JA] Infectious Diseases and Microbiology Unit, Hospital Universitario Virgen de Valme, Seville, Spain. [Lao-Dominguez,FA; Contreras-Macias,E; Gutierrez-Pizarraya,A; Morillo-Verdugo,R] Pharmacy, Hospital Universitario Virgen de Valme, Seville, Spain.
Keywords: COVID-19;Antiviral agents;Drug combinations;Drug Interactions;Lopinavir;Ritonavir;Spain;Antivirales;Combinación de medicamentos;Interacciones farmacológicas;Inhibidores de proteasas;España
metadata.dc.subject.mesh: Medical Subject Headings::Persons::Persons::Age Groups::Adult::Aged
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents
Medical Subject Headings::Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections
Medical Subject Headings::Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cross-Sectional Studies
Medical Subject Headings::Chemicals and Drugs::Pharmaceutical Preparations::Drug Combinations
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Pharmacological Processes::Drug Interactions
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyrimidines::Pyrimidinones::Lopinavir
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Persons::Persons::Age Groups::Adult::Middle Aged
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protease Inhibitors
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Sulfur Compounds::Thiazoles::Ritonavir
Medical Subject Headings::Geographical Locations::Geographic Locations::Europe::Spain
Issue Date: 1-Dec-2020
Publisher: Nature Publishing Group
Citation: Macías J, Pinilla A, Lao-Dominguez FA, Corma A, Contreras-Macias E, González-Serna A, et al. High rate of major drug–drug interactions of lopinavir–ritonavir for COVID-19 treatment. Sci Rep. 2020 Dec 1;10(1):20958
Abstract: The impact of drug-drug interactions (DDI) between ritonavir-boosted lopinavir (LPV-r) to treat patients with coronavirus disease 2019 (COVID-19) and commonly used drugs in clinical practice is not well-known. Thus, we evaluated the rate and severity of DDI between LPV-r for COVID-19 treatment and concomitant medications. This was a cross-sectional study including all individuals diagnosed of SARS-CoV-2 infection treated with LPV-r and attended at a single center in Southern Spain (March 1st to April 30th, 2020). The frequency [95% confidence interval (95% CI)] of potential and major DDI were calculated. Overall, 469 patients were diagnosed of COVID-19, 125 (27%) of them were prescribed LPV-r. LPV-r had potential DDI with concomitant medications in 97 (78%, 95% CI 69-85%) patients, and in 33 (26%, 95% CI 19-35%) individuals showed major DDI. Twelve (36%) patients with major DDI and 14 (15%) individuals without major DDI died (p = 0.010). After adjustment, only the Charlson index was independently associated with death [adjusted OR (95% CI) for Charlson index ≥ 5: 85 (10-731), p < 0.001]. LPV-r was discontinued due to side effects in 31 (25%) patients. Management by the Infectious Diseases Unit was associated with a lower likelihood of major DDI [adjusted odds ratio (95% CI): 0.14 (0.04-0.53), p = 0.003). In conclusion, a high frequency of DDI between LPV-r for treating COVID-19 and concomitant medications was found, including major DDI. Patients with major DDI showed worse outcomes, but this association was explained by the older age and comorbidities. Patients managed by the Infectious Diseases Unit had lower risk of major DDI.
metadata.dc.identifier.doi: 10.1038/s41598-020-78029-3
ISSN: 2045-2322
Appears in Collections:01- Artículos - Hospital de Valme

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