A woman in her 80s was brought to the emergency department for acute onset of generalised weakness, lethargy and altered mental state. The emergency medical service found her to have symptomatic bradycardia, and transcutaneous pacing was done. Medical history was notable for hypertension, hyperlipidaemia, type 2 diabetes, and a recently diagnosed SARS-CoV-2 (COVID-19) infection for which she was prescribed ritonavir-boosted nirmatrelvir (Paxlovid) two days before the presentation. On arrival at the hospital, she was found to have marked bradycardia with widened QRS, hyperglycaemia and metabolic acidosis. Transvenous pacing along with pressor support and insulin were initiated, and she was admitted to the intensive care unit. Drug interaction between ritonavir-boosted nirmatrelvir and verapamil leading to verapamil toxicity was suspected of causing her symptoms, and both drugs were withheld. She reverted to sinus rhythm on the fourth day, and the pacemaker was discontinued.
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http://dx.doi.org/10.1136/bcr-2022-252677 | DOI Listing |
Heliyon
January 2025
Department of Pharmacy, Shanghai Changhai Hospital, The First Affiliated Hospital of Naval Medical University, Shanghai, China.
Currently, the trials found that the clinical efficacy of molnupiravir is lower than ritonavir-boosted nirmatrelvir. An explanation for these different efficacies in clinical treatments is still limited. The analysis method was developed and validated to simultaneously quantify nirmatrelvir, ritonavir, and beta-D-N4-hydroxycytidine (NHC) in human plasma and bronchoalveolar lavage fluid (BALF) by electrospray ionization mass spectrometry.
View Article and Find Full Text PDFPNAS Nexus
January 2025
Department of Refractory Viral Diseases, National Center for Global Health and Medicine Research Institute, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
We identified a 5-fluoro-benzothiazole-containing small molecule, TKB272, through fluorine-scanning of the benzothiazole moiety, which more potently inhibits the enzymatic activity of SARS-CoV-2's main protease (M) and more effectively blocks the infectivity and replication of all SARS-CoV-2 strains examined including Omicron variants such as SARS-CoV-2 and SARS-CoV-2 than two M inhibitors: nirmatrelvir and ensitrelvir. Notably, the administration of ritonavir-boosted nirmatrelvir and ensitrelvir causes drug-drug interactions warranting cautions due to their CYP3A4 inhibition, thereby limiting their clinical utility. When orally administered, TKB272 blocked SARS-CoV-2 replication without ritonavir in B6.
View Article and Find Full Text PDFTranspl Infect Dis
January 2025
Division of Public Health, Infectious Diseases, and Occupational Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Background: Multiple outpatient therapies have been developed for COVID-19 in high-risk individuals, but solid organ transplant (SOT) recipients were not well represented in controlled clinical trials. To date, few comparative studies have evaluated outcomes between outpatient therapies in this population.
Methods: We performed a retrospective cohort study using de-identified administrative claims data from OptumLabs Data Warehouse.
BMC Infect Dis
December 2024
Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II, Naples, Italy.
Background: Ritonavir-boosted nirmatrelvir (N/r) is an antiviral which targets the main viral protease, administered to prevent the progression of SARS-CoV-2 infection in patients at high risk for severe COVID-19. We present a real-life case-control study evaluating the efficacy of N/r therapy in SARS-CoV-2 omicron variants positive outpatients in Campania region, Italy, with the aim of assessing the occurrence of three outcomes (hospital admission, admission in ICU and death) in cases and controls.
Methods: We enrolled SARS-CoV-2 positive subjects that came to our attention in Early antiviral treatment ambulatory of Infectious Diseases ward of University Federico II of Naples, Italy from January 1st, 2022, to December 31st, 2022, during the first five days from symptoms occurrence.
Nat Commun
June 2024
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
In a pivotal trial (EPIC-HR), a 5-day course of oral ritonavir-boosted nirmatrelvir, given early during symptomatic SARS-CoV-2 infection (within three days of symptoms onset), decreased hospitalization and death by 89.1% and nasal viral load by 0.87 log relative to placebo in high-risk individuals.
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