Famotidine use is associated with a reduced risk of clinical deterioration leading to intubation or death in patients who are hospitalized with coronavirus disease 2019 (COVID-19), according to a study published in Gastroenterology.
Famotidine, a histamine-2 receptor antagonist that suppresses gastric acid production, has inhibited human immunodeficiency virus replication in vitro and may inhibit the 3-chymotrypsin-like protease (3CLpro), which processes proteins essential for viral replication.
This retrospective cohort study of patients with COVID-19 aged 18 and older was conducted at a single academic center in New York City. Participants were eligible if they were admitted between February 25, 2020 and April 13, 2020 and tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 72 hours of admission. The primary outcome was a composite of death or endotracheal intubation from hospital day 2 to day 30.
A total of 1620 patients were included in the analysis; 84 patients received famotidine within 24 hours of hospital admission and 1536 did not. Famotidine doses were administered for a median of 5.8 days, resulting in a total median dose of 136 mg (63-233 mg).
Within the cohort, 142 (8.8%) patients were intubated, and 238 (15%) died; 340 (21%) patients met the composite study outcome. Crude analysis showed that famotidine use was significantly associated with a reduced risk for the composite outcome of death or intubation (log-rank P <.01).
“This association was driven primarily by the relationship between famotidine and death…and when those who died before intubation were excluded, there was no association between use of famotidine and intubation (log-rank P =.40),” the researchers wrote.
After adjustment for baseline patient characteristics, the study authors found that famotidine use remained independently associated with the risk of death or intubation (adjusted hazard ratio [HR] 0.42; 95% CI, 0.21-0.85). Propensity score matching was used to further balance the covariables, and this finding remained unchanged (HR 0.43; 95% CI, 0.21-0.88).
Investigators found no protective effect with use of proton pump inhibitors (PPIs; adjusted HR 1.34; 95% CI, 1.06-1.69). Additionally, among 784 patients without COVID-19 who were hospitalized during the study period, famotidine use was not associated with a reduced risk for death or intubation (24 deaths or intubations; log-rank P =.70). Users of famotidine had a lower peak ferritin value, which supports the hypothesis that famotidine may decrease cytokine release in SARS-CoV-2 infection.
Several study limitations were noted, including the single-center, observational design. The authors cannot exclude the possibility of unmeasured confounders or hidden biases that account for the association between famotidine use and improved outcomes.
“In patients hospitalized with COVID-19 and not initially intubated, famotidine use was associated with a 2-fold reduction in clinical deterioration leading to intubation or death,” the researchers concluded. “These findings are observational and should not be interpreted to mean that famotidine has a protective effect against COVID-19. Randomized controlled trials are under way.”
Freedberg DE, Conigliaro J, Wang TC, et al. Famotidine use is associated with improved clinical outcomes in hospitalized COVID-19 patients: a propensity score matched retrospective cohort study. Gastroenterology. 2020;159(3):1129-1131.e3. doi: 10.1053/j.gastro.2020.05.053