Macías, JuanPinilla, AnaLao-Dominguez, Francisco A.Corma, AnaïsContreras-Macias, EnriqueGonzález-Serna, AlejandroGutierrez-Pizarraya, AntonioFernández-Fuertes, MartaMorillo-Verdugo, RamónTrigo, MartaReal, Luis M.Pineda, Juan A.2021-12-272021-12-272020-12-01Macías 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):20958http://hdl.handle.net/10668/3438The 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.6 p.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/COVID-19Antiviral agentsDrug combinationsDrug InteractionsLopinavirRitonavirSpainAntiviralesCombinación de medicamentosInteracciones farmacológicasInhibidores de proteasasEspañaMedical Subject Headings::Persons::Persons::Age Groups::Adult::AgedMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral AgentsMedical Subject Headings::Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus InfectionsMedical Subject Headings::Health Care::Environment and Public Health::Public Health::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cross-Sectional StudiesMedical Subject Headings::Chemicals and Drugs::Pharmaceutical Preparations::Drug CombinationsMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Pharmacological Processes::Drug InteractionsMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyrimidines::Pyrimidinones::LopinavirMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Persons::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protease InhibitorsMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Sulfur Compounds::Thiazoles::RitonavirMedical Subject Headings::Geographical Locations::Geographic Locations::Europe::Spainresearch article33262433open access10.1038/s41598-020-78029-32045-2322PMC7708981