To clarify the safety profile of paracetamol for home-care patients with COVID-19: a real-world cohort study, with nested case–control analysis, in primary care
Francesco Lapi, Ettore Marconi, Ignazio Grattagliano, Alessandro Rossi, Diego Fornasari, Alberto Magni, Pierangelo Lora Aprile, Claudio Cricelli
Internal and Emergency Medicine, doi:10.1007/s11739-022-03054-1
Background and objective This study aimed to compare the prescribing patterns of paracetamol in COVID-19 with those for similar respiratory conditions and investigated the association between paracetamol use and COVID-19-related hospitalization/death. Methods Using a primary care data source, we conducted a cohort study to calculate the incidence rate of paracetamol use in COVID-19 and for similar respiratory conditions in 2020 and 2019 (i.e. pre-pandemic phase), respectively. In the study cohort, we nested a case-control analyses to investigate the association between paracetamol use and COVID-19-related hospitalizations/deaths. Results Overall, 1554 (33.4 per 1000) and 2566 patients (78.3 per 1000) were newly prescribed with paracetamol to treat COVID-19 or other respiratory conditions, respectively. Those aged 35-44 showed the highest prevalence rate (44.7 or 99.0 per 1000), while the oldest category reported the lowest value (17.8 or 39.8 per 1000). There was no association for early (OR = 1.15; 95% CI: 0.92-1.43) or mid-term (OR = 1.29; 95% CI: 0.61-2.73) users of paracetamol vs. non-users. Instead, the late users of paracetamol showed a statistically significant increased risk of hospitalization/death (OR = 1.75; 95% CI: 1.4-2.2). Conclusions Our findings provide reassuring evidence on the use and safety profile of paracetamol to treat early symptoms of COVID-19 as in other respiratory infections.
Supplementary Information The online version contains supplementary material available at https:// doi. org/ 10. 1007/ s11739-022-03054-1. Authors contribution FL, IG, AR, DF, EM, AM, PLA and CC: have made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data. FL, EM, IG, DF, PLR and CC: have been involved in drafting the manuscript or revising it critically for important intellectual content. CC: is responsible for the integrity of the work, and he given final approval of the version to be published. Each author should have participated sufficiently in the work to take public responsibility for appropriate portions of the content. FL: agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Conflict of interest FL and EM provided consultancies in protocol preparation for epidemiological studies and data analyses for Angelini, Pfizer, and GSK. AR, IG, AM, PLA, and CC provided clinical consultancies for Angelini, Pfizer, and GSK. DF has no conflict of interest to disclose.
Ethical approval According to a by-law on the classification and implementation of observational drug-related research, as issued by the Italian National Drug Agency (an entity belonging to the Italian Ministry of Health), the present study does not require approval by an Ethics Committee in Italy (Italian Drug Agency..
References
Bianchini, Brignoli, Cricelli C VIII Report Health Search
Collins, Reitsma, Altman, Moons, Transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD): the TRIPOD statement, J Clin Epidemiol,
doi:10.1016/j.jclinepi.2014.11.010Cricelli, Mazzaglia, Samani, Prevalence estimates for chronic diseases in Italy: exploring the differences between self-report and primary care databases, J Pub Health Med
Dimova, Hoet, Dinsdale, Nemery, Acetaminophen decreases intracellular glutathione levels and modulates cytokine production in human alveolar macrophages and type II pneumocytes in vitro, Int J Biochem Cell Biol,
doi:10.1016/J.BIOCEL.2005.03.005Dinnes, Deeks, Berhane, Rapid, point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2 infection, Cochrane Database Syst Rev,
doi:10.1002/14651858.CD013705.PUB2Dri, How to treat COVID-19 patients at home in the Italian context: an expert opinion, Infect Dis Rep,
doi:10.3390/IDR13010028Elliott, Whitaker, Bodinier, Predictive symptoms for COVID-19 in the community: REACT-1 study of over 1 million people, PLOS Med,
doi:10.1371/JOURNAL.PMED.1003777Enners, Gradl, Kieble, Utilization of drugs with reports on potential efficacy or harm on COVID-19 before, during, and after the first pandemic wave, Pharmacoepidemiol Drug Saf,
doi:10.1002/pds.5324Guglielmi, Bellia, Pecchioli, What is the actual epidemiology of familial hypercholesterolemia in Italy? Int J Cardiol, Evidence from a National Primary Care Database,
doi:10.1016/j.ijcard.2016.08.269Hempenius, Groenwold, De Boer, Drug exposure misclassification in pharmacoepidemiology: sources and relative impact, Pharmacoepidemiol Drug Saf,
doi:10.1002/pds.5346Kennon-Mcgill, Mcgill, Extrahepatic toxicity of acetaminophen: critical evaluation of the evidence and proposed mechanisms, J Clin Transl Res
Lapi, Domnich, Marconi, Predicting the risk of severe COVID-19 outcomes in primary care: development and validation of a vulnerability index for equitable allocation of effective vaccines, Expert Rev Vaccines,
doi:10.1080/14760584.2022.2019582Lapi, Simonetti, Michieli, Assessing 5-year incidence rates and determinants of osteoporotic fractures in primary care, Bone,
doi:10.1016/j.bone.2011.09.048Lawrenson, Williams, Farmer, Clinical information for research; the use of general practice databases, J Public Health Med
Orsini, Bellocco, Bottai, A tool for deterministic and probabilistic sensitivity analysis of epidemiologic studies, Stata J
Pandolfi, Chirumbolo, Home therapy of COVID-19 at the earliest may greatly prevent hospitalization, Basic Clin Pharmacol Toxicol,
doi:10.1111/bcpt.13650Pandolfi, Chirumbolo, Ricevuti, Home pharmacological therapy in early COVID-19 to prevent hospitalization and reduce mortality: time for a suitable proposal, Basic Clin Pharmacol Toxicol,
doi:10.1111/bcpt.13690Pandolfi, Simonetti, Ricevuti, Chirumbolo, Paracetamol in the home treatment of early COVID-19 symptoms: a possible foe rather than a friend for elderly patients?, J Med Virol
Prada, Santos, Baião, Risk of SARS-CoV-2 Infection and COVID-19 Severity Associated With Exposure to Nonsteroidal Anti-Inflammatory Drugs: Systematic Review and Meta-Analysis, J. Clin, Pharmacol
Schneeweiss, Sensitivity analysis and external adjustment for unmeasured confounders in epidemiologic database studies of therapeutics, Pharmacoepidemiol Drug Saf,
doi:10.1002/pds.1200Suter, Consolaro, Pedroni, A simple, home-therapy algorithm to prevent hospitalisation for COVID-19 patients: a retrospective observational matched-cohort study,
doi:10.1016/J.ECLINM.2021.100941Suter, Consolaro, Pedroni, A simple, hometherapy algorithm to prevent hospitalisation for COVID-19 patients: a retrospective observational matched-cohort study, EClinicalMedicine
Tamim, Monfared, Lelorier, Application of lag-time into exposure definitions to control for protopathic bias, Pharmacoepidemiol Drug Saf,
doi:10.1002/PDS.1360Tuccori, Convertino, Ferraro, The impact of the COVID-19 "Infodemic" on drug-utilization behaviors: implications for pharmacovigilance, Drug Saf,
doi:10.1007/S40264-020-00965-WVaja, Chan, Ferreira, The COVID-19 ibuprofen controversy: a systematic review of NSAIDs in adult acute lower respiratory tract infections, Br J Clin Pharmacol,
doi:10.1111/BCP.14514
