Use of Famotidine Associated With Improved Outcomes of Hospitalized COVID-19 Patients

In patients hospitalized with COVID-19 and not initially intubated, use of famotidine is associated with a 2-fold reduction in clinical deterioration leading to intubation or death, a retrospective study in Gastroenterology showed.

Kaplan-Meier plot showing (A) intubation-free survival and (B) survival through a maximum of 30 days after hospital admission, stratified by use of famotidine. Patients were included in the study if they survived without intubation for 2 days following hospital admission. Use of famotidine was classified as present if it was received within the first 24 hours following hospital admission (any dose, form of administration, or duration) and otherwise as absent. The at-risk time began on hospital day 2 (indicated with a dashed red line) and patients were followed until hospital day 30. This study design avoided potential for immortal time bias because the exposure was classified before the start of the at-risk period.

Famotidine is a histamine-2 receptor antagonist that suppresses gastric acid production. In vitro, famotidine inhibits HIV replication, and a computational study identified famotidine as a drug that might inhibit the 3-chymotrypsin-like protease of SARS-CoV-2, which processes proteins required for viral replication. Daniel E. Freedberg et al therefore investigated the outcomes of hospitalized patients with COVID-19 who were taking famotidine in a retrospective cohort study at a single academic center in the US.

Freedberg et al collected data from 1620 patients who tested positive for SARS-CoV-2 no more than 72 hours following admission; 84 of the patients (5.1%) had received famotidine (any dose, form of administration, or duration; median dose of 136 mg) within 24 hours of hospital admission. Patients were excluded if they died or were intubated within 48 hours following hospital admission. The primary outcome was a composite of death or endotracheal intubation from hospital day 2 to day 30 (intubation-free survival). A total of 142 (8.8%) patients were intubated and 238 (15%) died; 340 patients (21%) met the composite study outcome.

In crude analysis, use of famotidine was significantly associated with reduced risk for the composite outcome of death or intubation (see figure; log-rank P < .01). This association was mostly due to the relationship between famotidine and death (see figure; log-rank P < .01); when patients who died before intubation were excluded, there was no association between use of famotidine and intubation. After the authors adjusted for baseline patient characteristics, use of famotidine was independently associated with risk for death or intubation (adjusted hazard ratio 0.42, 95% CI, 0.21–0.85). This did not change after propensity score matching to balance covariables (hazard ratio 0.43, 95% CI 0.21–0.88).

Freedberg et al also analyzed use of proton pump inhibitors (PPIs), which also suppress gastric acid. They found no protective effect associated with use of PPIs (adjusted hazard ratio 1.34, 95% CI 1.06–1.69). Furthermore, among 784 patients without COVID-19 hospitalized during the same study period, famotidine was not associated with reduced risk for death or intubation.

How does famotidine reduce risk of death or intubation in patients with COVID-19? The authors propose that by blocking viral replication, famotidine reduces the cytokine storm during COVID-19. The median level of ferritin was 708 ng/mL (interquartile range 370–1152) among users of famotidine vs 846 ng/mL (interquartile range 406–1552) among nonusers (rank-sum P = .03).

Freedberg et al state that they assumed that the use of famotidine in this study was a continuation of home use, but documentation of why famotidine was given was poor. A letter to the editor from Vijay P. Singh et al further discusses formulations and mechanisms of famotidine in patients.

A randomized controlled trial is underway to determine whether famotidine can improve clinical outcomes in hospitalized patients with COVID-19 (NCT04370262).

1 Comment

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    Moshe Rogosnitzky October 04, 2020

    This is one of a few papers that support the use of famotidine for COVID-19. Sadly, there appears to be a “war” between two groups each claiming to have originated the idea of using famotidine for COVID-19.

    If you check on PubMed I was privileged to submit the first article, on April 7th, proposing the use of famotidine for COVID-19 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224168/

    The fact that both groups who subsequently published have failed to accurately cite the scientific record, is regrettable. This could be overlooked if instead of arguing about who deserves the credit, all parties would harness much-needed efforts in designing trials to elucidate the dose needed, and quantify famotidine’s benefits, for the health of humankind everywhere.

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