Famotidina en el tratamiento de pacientes hospitalizados con COVID-19. Revisión sistemática y metaanálisis / Famotidine in the treatment of hospitalized patients with COVID-19. Systematic review and meta-analysis

Introducción: El síndrome respiratorio agudo severo coronavirus 2 (SARS-CoV-2), de alta morbimortalidad, carece a la fecha de preparar esta revisión, de una terapia específica altamente eficaz. Famotidina se ha postulado como una opción terapéutica viable, basado en trabajos de cohorte retrospectiva y modelos computacionales guiados por inteligencia artificial. Objetivo: Recopilar la mejor evidencia científica disponible para determinar la efectividad y eficacia de famotidina en el tratamiento de pacientes hospitalizados con COVID-19, para reducir el riesgo de progresión de la enfermedad, intubación, muerte y tiempo de estancia hospitalaria. Material y Métodos: Se realizó una búsqueda en PubMed, EBSCO, Scopus, Web of Science y Cochrane Central, de artículos originales que reporten las variables de interés asociadas al uso de famotidina en pacientes hospitalizados con COVID- 19. Los investigadores independientemente evaluaron y seleccionaron los estudios, se extrajeron los datos expuestos para las asociaciones de interés y se procesaron con el software Revman 5.3. Resultados: En la búsqueda se obtuvo un total de 126 artículos potenciales para la revisión, de los cuales 14 fueron seleccionados para el análisis. En el metaanálisis se incluyeron un total de 47.044 pacientes, de los cuales 6.647 fueron los usuarios de famotidina. El riesgo de intubación se vio reducido en el grupo no expuesto a famotidina, aunque sin significancia estadística, (RR 1,43 IC95% 0,42-4,83), en cuanto a la mortalidad no se evidenció reducción significativa en el grupo de famotidina (RR 0,95 IC 95% 0,70-1,29). Se observó reducción en el tiempo de estancia hospitalaria (DM -1,60 -2,89, -0,31) y finalmente se mostró que no hay presencia de asociación entre el uso de famotidina y el desenlace compuesto de reducción del riesgo de ingreso a UCI, intubación y muerte (RR 1,03 IC 95% 0,46-2,34). Conclusión: Famotidina no presenta efectividad ni eficacia en la reducción de riesgo de intubación o ingreso a UCI ni de mortalidad en pacientes hospitalizados por COVID-19. La eficacia en la reducción de la estancia hospitalaria no es consistente y se necesitan más ensayos clínicos con buena calidad metodológica para definirla.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with high morbidity and mortality, lacks, at the time of preparing this review, a highly effective specific therapy. Famotidine has been postulated as a viable therapeutic option, based on retrospective cohort investigations and computational models guided by artificial intelligence. Aim: The objective of this study was to compile the best scientific evidence available to determine the effectiveness and efficacy of famotidine in the treatment of hospitalized patients with COVID-19, to reduce the risk of disease progression, intubation, death, and time to hospital stay. Methods: A search was carried out in PubMed, EBSCO, Scopus, Web of Science, and Central Cochrane, for original articles that report the variables of interest associated with the use of famotidine in hospitalized patients with COVID-19. The investigators independently evaluated and selected the studies, the exposed data for the associations of interest were extracted and processed with Revman 5.3 software. Results: The search yielded a total of 126 potential articles for the review, of which 14 were selected for analysis. A total of 47,044 patients were included in the meta-analysis of which 6,647 were famotidine users. The risk of intubation was reduced in the group not exposed to famotidine, although without statistical significance (RR 1.43 IC95% 0.42 - 4.83), regarding mortality there was no significant reduction in the famotidine group (RR 0.95 IC 95 % 0.70-1.29). A reduction in the length of hospital stay was observed (MD -1.60 -2.89, -0.31) and finally it was shown that there is no association between the use of famotidine and the composite outcome of reduced risk of ICU admission, intubation and death. (RR 1.03 95% CI 0.46-2.34). Conclusion: Famotidine does not show effectiveness or efficacy in reducing the risk of intubation or ICU admission or mortality in patients hospitalized for COVID-19. The efficacy in reducing hospital stay is not consistent and more clinical trials with good methodological quality are needed to define it.

Informe diário de evidências COVID-19: busca realizada entre 6 e 8 de junho de 2020 / COVID-19 daily evidence report: search conducted between 6 and 8 June 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 13 artigos.

Informe diário de evidências COVID-19: busca realizada em 29 de abril de 2020 / COVID-19 daily evidence report: search conducted on April 29, 2020

Essa é uma produção do Departamento de Ciência e Tecnologia (Decit) da Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde (SCTIE) do Ministério da Saúde (Decit/SCTIE/MS), que tem como missão promover a ciência e tecnologia e o uso de evidências científicas para a tomada de decisão do SUS, tendo como principal atribuição o incentivo ao desenvolvimento de pesquisas em saúde no Brasil, de modo a direcionar os investimentos realizados em pesquisa pelo Governo Federal às necessidades de saúde pública. Informar sobre as principais evidências científicas descritas na literatura internacional sobre tratamento farmacológico para a COVID-19. Além de resumir cada estudo identificado, o informe apresenta também uma avaliação da qualidade metodológica e a quantidade de artigos publicados, de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, entre outros). Foram encontrados 13 artigos e 7 protocolos.

Rebamipide May Be Comparable to H2 Receptor Antagonist in Healing Iatrogenic Gastric Ulcers Created by Endoscopic Mucosal Resection: A Prospective Randomized Pilot Study

Endoscopic mucosal resection (EMR) results in the formation of iatrogenic gastric ulcers and the optimal treatments for such ulcers are still unclear. We aimed to evaluate the efficacy of rebamipide in the management of EMR-induced ulcers by comparing it with an H2 receptor antagonist. After EMR, patients were randomly assigned into either rebamipide or famotidine groups. All patients received a one-week lansoprazole 30 mg q.d. therapy followed by three-week famotidine (20 mg b.i.d.) or rebamipide (100 mg t.i.d.) therapy. Four weeks after the treatments, ulcer sizes, stages, bleeding rates, and ulcer-related symptoms were compared using endoscopy and a questionnaire. A total of 63 patients were enrolled in this study. Finally, 51 patients were analyzed, 26 in rebamipide and 25 in famotidine group. Baseline characteristics were not significantly different between the two groups. Four weeks after EMR, the two groups were comparable in terms of ulcer reduction ratio (P=0.297), and ulcer stage (P=1.000). Moreover, no difference was observed with regard to ulcer-related symptoms, drug compliance, adverse drug event rates, and bleeding rates. Our data suggest that rebamipide is not inferior to famotidine in healing iatrogenic gastric ulcers, and could be a therapeutic option in the treatment of such ulcers.

A Prospective Randomized Trial of Either Famotidine or Pantoprazole for the Prevention of Bleeding after Endoscopic Submucosal Dissection

Endoscopic submucosal dissection (ESD) has been reported to have a higher bleeding rate than conventional methods. However, there are few reports on whether a proton pump inhibitor or a histamine2-receptor antagonist is the more effective treatment for preventing bleeding after ESD. In a prospective trial, patients undergoing ESD due to gastric adenoma or adenocarcinoma were randomly assigned to pantoprazole or famotidine. Both drugs were given intravenously for the first 2 days, thereafter by mouth. Eighty-five in the pantoprazole group and 79 in the famotidine group were included for analysis. Primary outcome measure was the delayed bleeding rate. Clinical characteristics were not different between the two groups. The delayed bleeding rate was significantly lower in the pantoprazole group compared with the famotidine group (3.5% vs. 12.7%, p=0.031). On multivariate analysis, the preventive use of pantoprazole (relative hazard: 0.220, 95% CI: 0.051- 0.827, p=0.026) and the specimen size (> or =34 mm, relative hazard: 4.178, 95% CI: 1.229-14.197, p=0.022) were two independent factors predictive of delayed bleeding. There were no significant differences in en bloc and complete resection rate between the two groups. In conclusion, pantoprazole is more effective than famotidine for the prevention of delayed bleeding after ESD.

Effect of preoperative short course famotidine on TILs and survival in breast cancer.

BACKGROUND: Histamine receptor antagonists have been shown to induce tumor-infiltrating lymphocytes (TILs) in colonic cancers and improve survival. The role of histamine receptor anatagonists in breast cancer is unclarified. AIM: To evaluate the role of histamine receptor antagonists in inducing (TILs) in breast cancer. METHOD: Forty-five patients with operable breast cancers (25 cases who received preoperative famotidine and 20 controls) were studied for the effect of famotidine in inducing TILs and survival in breast cancer. RESULTS: Significant TILs were seen in 75% (18/24) of cases as opposed to 35% (7/20) controls. In logistic regression analysis the only variable found to be predictive of TILs was famotidine, odds ratio 7.324 (1.693-31.686) P=0.008. In Cox's regression presence of TILs was favorably associated with improved disease free survival at a median follow up of 35.56 months. The hazard ratio for disease relapse was 3.327 (1.174-9.426) P=0.024 in TIL negative as compared to TIL positive patients. Famotidine use alone was not significant in the original model, however, on incorporation of quadrant of involvement in addition to other established prognostic factors in the above multivariate model, it assumed borderline significance with a hazard ratio for disease free survival 3.404 (1.005-11.531, P=0.049). CONCLUSIONS: Preoperative short course famotidine induces TILs in breast cancer. Patients with TILs demonstrable in tumor specimens had an improved disease free survival. Famotidine may improve disease free survival in breast cancer and these findings need validation in larger population subsets.

Antiinflammatory and antiulcer activities of phytic acid in rats.

Maximum antiinflammatory activity of phytic acid (PA) was seen at an oral dose of 150 mg/kg in the carrageenan induced rat paw edema model. Although PA showed ability to prevent denaturation of proteins, it showed less antiinflammatory activity than ibuprofen. Ability of PA to bring down thermal denaturation of proteins might be a contributing factor in the mechanism of action against inflammation. PA, at all the doses tested, showed significant protection from ulcers induced by ibuprofen, ethanol and cold stress, with a maximum activity at 150 mg/kg. There was a significant increase in gastric tissue malondialdehyde levels in ethanol treated rats but these levels decreased following PA pretreatment. Moreover, pretreatment with PA significantly inhibited various effects of ethanol on gastric mucosa, such as, reduction in the concentration of nonprotein sulfhydryl groups, necrosis, erosions, congestion and hemorrhage. These results suggested that gastro-protective effect of PA could be mediated by its antioxidant activity and cytoprotection of gastric mucosa.

Healing-promoting action of rhinax with dual action on chronic gastric and duodenal ulcers induced by acetic acid in rats.

Healing promoting actions of Rhinax, a multiconstituent herbal preparation, was investigated in chronic gastric and duodenal ulcer models induced by acetic acid in rats and the effects were compared with those of famotidine by gross of histological evaluation. Rhinax markedly promoted the well balanced healing of gastric ulcer at oral does of 25-100 mg/kg x 2 /day, as evidenced by the reduction of ulcer, regeneration of mucosa and proliferation of connecitve tissue. Rhinax caused an increase in gastric mucosa secretion in all the regenerated mucosa around the gastric ulcers. Famotidine failed to promote the healing of gastric ulcers at 100 mg/kg x 2/ day p.o. Rhinax also significantly accelerated the healing of acetic acid -induced duodenal ulcers as well famotidine. These results indicate that Rhinax is characterised by a potent promoting action on the healing of chronic ulcers, suggesting that the increase in gastric mucus secretion might be associated with the antiulcer action of Rhinax in rats.

Famotidina versus placebo en el tratamiento de la dispepsia no ulcerosa / Famotidine versus placebo in non ulcer dyspepsia treatment

La dispepsia no ulcerosa una entidad de alta prevalencia cuya patogenicidad no es clara aún, siendo su asociación con el helicobacter pylori altamente controversial. Se han realizado numerosos estudios acerca de su tratamiento, uno de los esquemas más comúnmente usados son los antagonistas H2, sin embargo los resultados son conflictivos en cuanto a su eficacia. El objetivo del presente estudio es determinar la eficacia de famotidina (en tres regímenes diferentes) comparada con placebo en aliviar los síntomas de la dispepsia no ulcerosa. Material y métodos: Se incluyeron pacientes con dispepsia crónica no ulcerosa que fueron randomizados en 4 grupos; el grupo I recibió famotidina 40 mg, antes del desayuno, placebo antes del almuerzo y al acostarse. El grupo II famotidina 20 mg, antes del desayuno y antes del almuerzo, placebo al acostarse. El grupo III recibió famotidina 40 mg al acostarse, placebo antes del desayuno y antes del almuerzo. El grupo IV recibió placebo antes del desayuno, antes del almuerzo y al acostarse. El periodo de tratamiento fue de 4 semanas. Al inicio del estudio, en la cuarta y octava semana se les realizó una endoscopía, se midió el pH del jugo gástrico y se tomaron biopsias gástricas para el estudio anátomo patológico(incluido el estudio para Helicobacter pylori). El paciente realizaba una evaluación de la mejoría de sus sintomas al finalizar la primera, cuarta y octava semana de haber empezado el tratamiento y se compararon los resultados. Resultados: En total participaron 48 pacientes en el estudio, 12 hombres y 36 mujeres. No se halla diferencia significativa entre los esquemas de tratamiento y su efectos sobre la evolución del dolor y de los síntomas en el transcurso del estudio, sin embargo se observa una diferencia altamente significativa (P menor 0.01) de la mejoría del paciente en el tiempo, independientemente del esquema de tratamiento recibido. Se halla una diferencia significativa (p menor 0.05) entre los pH de los grupos II, III y IV, siendo mayor el valor promedio de pH a la cuarta semana. No se halla diferencia significativa del valor del pH entre los pacientes que mejoraron y los que no mejoraron sus síntomas. La densidad del Hp permaneció sin variaciones significativas a lo largo del estudio, tanto en el grupo de pacientes que experimentó mejoría del dolor y los síntomas asociados, como en el grupo que no mejoró...

Reflujo faringolaríngeo: una patología con identidad propia / Pharyngolaryngeal reflux: a pathology with a distinctive identity

Se presenta un grupo compuesto por 70 pacientes portadores de síntomas atribuibles a reflujo faringolaríngeo y 20 pacientes controles. Se describen y proponen 3 estadios clínocos nasofibroscópicos de la enfermedad y se correlacionan con los síntomas digestivos, broncopulmonares y faringolaríngeos en los pacientes y controles. En los 70 pacientes se analizan los resultados del tratamiento médico propuesto, siendo bueno en el 88,4 por ciento de los casos y regular en 11,6 por ciento

A randomized clinical trial comparing the efficacy of ranitidine and famotidine on intragastric acidity in critically ill pediatric patients.

We examined the efficacy of intravenous ranitidine and famotidine on raising intragastric pH in each of 10 critically ill pediatric patients. The severity of illness was assessed by using the modified zinner index score. The study had 3 phases and each phase took 24 hours. Intragastric pH was measured by continuous pH monitoring digitrapper for 72 hours. In phase 1 and 3, the patients did not receive any H2 blockers. In phase 2, they were randomized to receive intravenous ranitidine or famotidine. The majority of cases had intragastric pH < 4 in day 1 (base line). Ranitidine and famotidine increased total time of intragastric pH > or = 4 from the base line during day 2, 38.2 +/- 16.9 per cent and 60.3 +/- 24.8 per cent respectively (P0.004), but there was no statistical difference between the 2 medications in both Zinner index score 1 and score greater than 1 group (P 0.08, 0.45). Three cases in the famotidine group had successful prophylaxis with total time pH > or = 4 more than 80 per cent. Famotidine appeared to have a trend toward increasing intragastric pH in critically ill pediatric patients.

Erradicación de helicobacter pylori en países en desarrollo / Eradication of helicobacter pylori in developing countries

A NIH Consensus Conference recommended Helicobacter pylori eradication to all ulcer patients, based mainly on information coming from countries with a low prevalence of infection in general population. The epidemiological situation is different in developing countries, where a pandemic of H., pylori goes unchecked, and most people become infected at young age. It is possible that response to eradication therapies and reinfection rate were to be included among the differences between developed and developing countries, raising doubts about the worldwide applicability of NIH recommendations. Limited published evidence and out experience suggest that eradication therapies have a lower efficacy and reinfection rate is significantly higher in developing compared to developed countries. In spite of this, the risk of ulcer recurrence after H. pylori eradication is substantially reduced compared to antisecretory therapy. Model analysis to evaluate the cost-effectiveness of H. pylori eradication, using figures that probably include the clinical and cost situation of developing countries, suggests that also from an economic perspective H. pylori eradication should be the standard treatment for peptic ulcer disease in developing countries. Local studies must determine the best eradication therapy for a particular geographical location, and longer follow-up of eradicated patients is needed to determine the true reinfection rate

Cambio de la historia natural de la úlcera duodenal después de la erradicación de helicobacter pylori: estudio aleatorio, doble ciego, controlado con placebo: seguimiento de 44 meses / Helicobacter Pylori eradication changes the natural history of peptic ulcer disease: randomised, doble-blind, placebo control trial: 44 months of follow up

Evaluamos 63 pacientes (p) con úlcera duodenal (UD) e infección por Helicobacter Pylori (Hp) detectada mediante biopsia del antro gástrico con las pruebas de: Ureasa, cultivo, Gram, y estudio histológico con tinsiones de hematoxilina-eosina y de Warthin-starry. A todos se les suministró famotidina 40mg vía oral durante seis semanas. En los primeros diez días, a 30p se les suministró placebo (GP) y a 33p el (GT) metronidazol 250mg más amoxicilina 500mg TID c/u. Se realizaron controles endoscópicos a las 6 semanas, c/3 meses en el primer año, c/6 meses por dos años y luego anualmente. La cicatrización no mostró diferencias pero la recurrencia a partir de los tres meses fue mayor en el GP 68,75 vs 11,76 por ciento GT (p= 0,001). Al año todo el GP recidivó y solamente 4/24p del Gt (16,66 por ciento). A los 44 meses el GT persistió con baja rata de recurrencia (25 por ciento). Helicobacter Pylori se demostró cada vez que la UD apareciió, y se logró erradicar en 62,5 por ciento del GT. Nuestros resultados sugieren que la recidiva de la UD se asocia a infección por Hp y que en los pacientes en quienes se erradica la bacteria se logra cambiar la historia natural de la enfermedad ulcerosa al disminuir significativamente la recurrencia

Estudo multicentrico da famotidina em patologias digestivas altas / Famotidine multicenter study

Um estudo multicentrico realizado em 20 estados do Brasil foi conduzido para determinar a eficacia terapeutica e a tolerancia da famotidina, um antagonista do receptor H2, no tratamento da ulcera duodenal gastrica, da esofagite e da dispepsia nao ulcerosa. 1321 pacientes receberam uma dose oral unica de 40 mg de famotidina ao deitar, durante quatro semanas.A eficacia e a seguranca da famotidina no tratamento das patologias foram avaliadas atraves da melhora da sintomatologia (dor, pirose, vomitos) e por endoscopia pre e pos-tratamento em todos os pacientes.A endoscopia mostrou a cicatrizacao completa das ulceras em 96 por cento dos casos, regressao completa da esofagite em 92 por cento dos casos e observou-se cura completa da sintomatologia da dispepsia nao ulcerosa em 72 por cento dos casos.A tolerabilidade global foi considerada excelente na opiniao de 93 por cento dos medicos e pacientes.Foram registrados reacoes adversas em 5,53 por cento dos casos, sendo que 86,25 por cento destes foram considerados como de intensidade leve e moderada.Em face destes resultados conclui-se que a famotidina e eficaz e segura no tratamento das patologias digestivas altas.

Comparative study of omeprazole and famotidine in the treatment of duodenal ulcer.

In a double blind, multicenter, parallel group clinical trial in patients with symptomatic duodenal ulcers, 129 patients were randomized to receive either omeprazole 20 mg once daily (n = 65) or famotidine 40 mg once daily (n = 64) for 2 weeks, and if the ulcers were not healed, for a total of 4 weeks. Seventy four percent of these receiving omeprazole had healed ulcers after 2 weeks compared with 34.3% of those receiving famotidine (p < 0.001). At 4 weeks, the respective figures were 97.3% and 77.6% (p < 0.001). After 2 weeks of treatment, only 11.1% and 29.8% of omeprazole and famotidine treated patients respectively had day time pain (p < 0.02). Diary cards (successfully completed by 2/3rd of patients) showed that omeprazole treated patients required smaller amounts of antacids (p = ns). Over the first two weeks, ulcer healing rate was similar in smokers and non- smokers. No significant side effects were reported in either group. Omeprazole 20 mg/day provides more rapid relief of symptoms and heals a greater proportion of duodenal ulcers at 2 and 4 weeks than famotidine 40 mg/day.

Famotidina en el tratamiento agudo y de mantenimiento de úlcera duodenal / Famotidina in the acute and the support treatment for duodenal ulcer

16 pacientes entre 46 y 78 años, nueve varones y siete mujeres, fueron tratados con 20mg. de Famotidina, como dosis de mantenimiento, durante un año, todos ellos previamente curados en el lapso de ocho semanas con la dosis habitual (40mg.) y antiácidos, de lesiones agudas duodenales. En todos los casos, curaron sus lesiones primigenias en ocho semanas (cuatro en cuatro semanas). Todos completaron el tratamiento por un año. Catorce de ellos llegaron al año sin lesiones. Uno con erosión gástrica. Uno mantuvo durante todo el tratamiento una duodenitis superficial asintomática. Cuatro pacientes hicieron recidivas ulcerosas intratamiento que curaron sin alterar el mismo. Los sintomas mas frecuentes que permanecieron en el tiempo: Cefalea y flatulencia. De los 16 pacientes 14 terminaron curados, dos con lesiones gástricas, uno con duodenitis no resuelta durante todo el tratamiento (asintomático) y cuatro hicieron recidivas intratamiento

Famotidina en úlcera duodenal aguda

Se trataron con Famotidina (MK-208=Pepcidine M.S.D.), 40 mg nocturnos, 37 pacientes con diagnóstico endoscópico de úlcera doudenal, de los cuales el 82.4 por ciento mostraron una respuesta excelente, siendo buena en el resto. Desde el punto de vista endoscópico, las úlceras que cicatrizaron lo hicieron entre la cuarta y sexta semana de tratamiento. En ninguno de los pacientes se observaron efectos colaterales mayores y los exámenes de laboratorio fueron normales antes y después del tratamiento

Tratamiento de la úlcera gástrica con sucralfato y famotidina / Treatment of gastric ulcer: sucralfate vs famotidine

We conducted a double blind random study on 79 patients with gastric ulcer: 39 received sucralfate, 1 g 4 times a day (Group 1) and 40 received a single evening dose of famotidine, 40 mg (Group 2). At 4 weeks, endoscopy revealed healing of the ulcer in 46% of patients in Group1 and 40% in group 2 (NS). At 8 weeks, corresponding figures were 90% and 75 (NS). All patients were able to complete treatment and minor side effects were reported from all patients, 36% with sucralfate and 28% with famotidine. Thus, sucralfate and famotidine are equally effective for therapy of gastric ulcer. The higher percentage of helaing with sucralfate observed in this study was not statistically significant