Pharmacological therapy with azithromycin, hydroxychloroquine and ivermectin increased gastrointestinal side effects in a population in northeast Brazil
DOI:
https://doi.org/10.53660/PRW-1807-3432Palavras-chave:
Covid-19, Diarréia, Prescrição de medicamentos, GastroenterologiaResumo
O surgimento da pandemia de COVID-19 impulsionou o consumo de combinações de medicamentos como o Kit COVID Brasileiro composto por azitromicina, hidroxicloroquina e ivermectina. Os efeitos dessas drogas no trato gastrointestinal permanecem incertos, motivando este estudo. Foi realizado um estudo epidemiológico transversal analítico e quantitativo em pacientes (n=124) da macrorregião costeira do estado do Piauí, Brasil, com diagnóstico confirmado de COVID-19, no período de fevereiro e agosto de 2021. Os sintomas gastrointestinais foram avaliados por meio do questionário Gastrointestinal Symptom Rating Scale (GSRS). A renda mostrou-se um fator na escolha do tratamento. Entre os 15 domínios do GSRS, os escores de dor abdominal, dor de fome, diarreia e urgência defecar foram significativamente maiores (p<0,05) no grupo de tratamento do que no grupo não tratado. Em relação às síndromes avaliadas, apenas as síndromes diarreicas apresentaram diferença significativa de frequência entre os grupos. O uso de medicamentos do Kit COVID associado ao desenvolvimento de sintomas gastrointestinais destaca a importância de considerar os potenciais efeitos adversos dos medicamentos em pacientes diagnosticados com COVID-19.
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Referências
ANDREANI, J. et al. In vitro testing of combined hydroxychloroquine and azithromycin on SARS-CoV-2 shows synergistic effect. Microbial pathogenesis, v. 145, p. 104228, 2020.
ARRUDA, E. A. G. et al. Clinical Features, Pathobiology, Efficacy, and Toxicity of Tenofovir Disoproxil Fumarate and Emtricitabine for Mild to Moderate SARS COV 2 Infections. European Journal of Respiratory Medicine, v. 3, n. 3, p.
-248, 2021.
ASAI, S. et al. Influence of methotrexate on gastrointestinal symptoms in patients with rheumatoid arthritis. International Journal of Rheumatic Diseases, v. 22, n. 2, p. 207-213, 2019.
BRASIL. Ministério da Saúde. Nota Informativa Nº 17/2020- SE/GAB/SE/MS. Orientações do Ministério da Saúde para Manuseio Medicamentoso Precoce de Pacientes com Diagnóstico da COVID-19. Ministério da Saúde, Brasília, DF, 11 ago. 2020. Disponível em: https://www.gov.br/saude/pt-br/centrais-de-conteudo/publicacoes/estudos-e-notas-informativas/2020/old-file-removed-covid-05mar2021-11h37.pdf/view. Acesso em: 25 ago. 2020.
CDC.Centers for Disease Control and Prevention. Rapid increase in ivermectin prescriptions and reports of severe illness associated with use of products containing ivermectin to prevent or treat COVID-19. CDC Health Alert Network no. CDCHAN-00449, v. 8, p. 26, 2021.
CFF. Conselho Federal de Farmácia. Notícia: Venda de Remédios sem eficácia comprovada. 2021. Disponível em: https://cff.org.br/noticia.php?id=6197&titulo=Venda+de+remédios+sem+eficácia+comprovada+contra+a+Covid+dispara. CFF, 2020. Acesso em: 23 de nov. 2022
CFM. Conselho Federal de Medicina. Parecer nº 4/2020: Tratamento de pacientes portadores de COVID-19 com cloroquina e hidroxicloroquina. Disponível em: https://sistemas.cfm.org.br/normas/visualizar/pareceres/BR/2020/4. Acesso em: 07 jun 2021.
CHOWDHURY, A. T. M. M. et al. A Randomized Trial of Ivermectin-Doxycycline and Hydroxychloroquine-Azithromycin therapy on COVID19 patients. Research Square. p. 1-19, 2020.
CIOTTI, M. et al. The COVID-19 pandemic. Critical reviews in clinical laboratory sciences, v. 57, n. 6, p. 365-388, 2020.
DE BENEDETTI, G.; VAIANO, A. S. Oral azithromycin and oral doxycycline for the treatment of Meibomian gland dysfunction: A 9-month comparative case series. Indian Journal of Ophthalmology, v. 67, n. 4, p. 464-471, 2019.
ELFAKHARANY, Y. M. et al. Possible Hepatotoxic Effects In Adult Male Albino Rats On Combination Of Ivermectin And Paracetamol Drugs Used In COVID-19 Infection Management Protocol. Egyptian Society of Clinical Toxicology Journal, v. 9, n. 2, p. 13-28, 2021.
FADEL, R. et al. Early short-course corticosteroids in hospitalized patients with COVID-19. Clinical Infectious Diseases, v. 71, n. 16, p. 2114-2120, 2020.
FONSECA, S. N. S. et al. Risk of hospitalization for Covid-19 outpatients treated with various drug regimens in Brazil: comparative analysis. Travel medicine and infectious disease, v. 38, p. 101906, 2020.
FURLAN, L.; CARAMELLI, B. The regrettable story of the “Covid Kit” and the “Early Treatment of Covid-19” in Brazil. The Lancet Regional Health–Americas, v. 4, 2021.
GÉRARD, A. et al. “Off-label” use of hydroxychloroquine, azithromycin, lopinavir-ritonavir and chloroquine in COVID-19: a survey of cardiac adverse drug reactions by the French Network of Pharmacovigilance Centers. Therapies, v. 75, n. 4, p. 371-379, 2020.
KING, C. R. et al. Inhibition of human adenovirus replication by the importin α/β1 nuclear import inhibitor ivermectin. Journal of Virology, v. 94, n. 18, p. 10.1128/jvi. 00710-20, 2020.
LIU, J. et al. Corticosteroid treatment in severe COVID-19 patients with acute respiratory distress syndrome. The Journal of clinical investigation, v. 130, n. 12, p. 6417-6428, 2020.
LOFGREN, S. M.M. et al. Safety of Hydroxychloroquine among Outpatient Clinical Trial Participants for COVID-19. medRxiv, 2020.
MAHMOUDI, J. et al. Nephrotoxicity of chloroquine and hydroxychloroquine in COVID-19 Patients. Advanced Pharmaceutical Bulletin, v. 11, n. 1, p. 6-7, 2020.
MENDONÇA, J. C. et al. Gastrointestinal effects of ivermectin treatment in rats infected with Strongyloides venezuelensis. Acta tropica, v. 194, p. 69-77, 2019.
MERCURO, N. J. et al. Risk of QT interval prolongation associated with use of hydroxychloroquine with or without concomitant azithromycin among hospitalized patients testing positive for coronavirus disease 2019 (COVID-19). JAMA cardiology, v. 5, n. 9, p. 1036-1041, 2020.
MILLION, M. et al. Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: a retrospective analysis of 1061 cases in Marseille, France. Travel medicine and infectious disease, v. 35, p. 101738, 2020.
OLDENBURG, C. E. et al. Effect of oral azithromycin vs placebo on COVID-19 symptoms in outpatients with SARS-CoV-2 infection: a randomized clinical trial. Jama, v. 326, n. 6, p. 490-498, 2021.
RENDIC, S. P. Metabolism and interactions of Ivermectin with human cytochrome P450 enzymes and drug transporters, possible adverse and toxic effects. Archives of Toxicology, v. 95, n. 5, p. 1535-1546, 2021.
SILVERMAN, M. A.; KONNIKOVA, L.; GERBER, J. S. Impact of antibiotics on necrotizing enterocolitis and antibiotic-associated diarrhea. Gastroenterology Clinics, v. 46, n. 1, p. 61-76, 2017.
SOUZA, A. Mapas em representação tridimensional. Confins. Revue franco-brésilienne de géographie/Revista franco-brasilera de geografia, n. 47, 2020.
SOUZA, G. S. et al. Translation and validation of the Brazilian Portuguese version of the gastrointestinal symptom rating scale (Gsrs) Questionnaire. Arquivos de Gastroenterologia, v. 53, n. 3, p. 146-151, 2016.
SRINIVASA, A.; TOSOUNIDOU, S.; GORDON, C. Increased incidence of gastrointestinal side effects in patients taking hydroxychloroquine: a brand-related issue?. The Journal of rheumatology, v. 44, n. 3, p. 398-398, 2017.
VELAVAN, T.; MEYE, C. The COVID‐19 epidemic. Trop Med Int Health. v. 25, n. 3, p. 278-80, 2020.
OMS. Organização Mundial de Saúde. Coronavirus disease 2019 (COVID-19) situation report-97 [Internet]. World Health Organization, [report 97; 2020 April 26]. [cited 2021 Jun 07]. Available from: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200426-sitrep-97-covid-19.pdf.
WONG, A. O. et al. Adverse effects of hydroxychloroquine and azithromycin on contractility and arrhythmogenicity revealed by human engineered cardiac tissues. Journal of Molecular and Cellular Cardiology, v. 153, p. 106-110, 2021.
WU, F. et al. A new coronavirus associated with human respiratory disease in China. Nature, v. 579, n. 7798, p. 265-269, 2020.
YEOH, Y. K. et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut, v. 70, n. 4, p. 698-706, 2021.
YETKIN, E.; YALTA, K.; WALTENBERGER, J. An antiarrhythmic approach to hydroxychloroquine-induced QT prolongation. Netherlands Heart Journal, v. 28, n. 7, p. 437-438, 2020.
