Famotidine is a histamine-2 receptor antagonist that suppresses gastric acid production. It has an excellent safety profile. Initially it was thought to inhibit the 3-chymotrypsin-like protease (3CLpro), but it seems to act rather as an immune modulator, via its antagonism or inverse-agonism of histamine signaling. While results of the randomized clinical trial on the benefits of intravenous famotidine in treating COVID-19 (NCT04370262) are eagerly awaited, we can only speculate on the potential mechanisms of action of this drug (Singh 2020).

  • In a retrospective study on 1620 patients, 84 (5.1%) received different doses of famotidine within 24 hours of hospital admission (Freedberg 2020). After adjusting for baseline patient characteristics, use of famotidine remained independently associated with risk for death or intubation (adjusted hazard ratio 0.42, 95% CI 0.21-0.85) and this remained unchanged after careful propensity score matching to further balance the co-variables. Of note, there was no protective effect of PPIs. Plasma ferritin values during hospitalization were lower with famotidine, indicating that the drug blocks viral replication and reduces the cytokine storm.
  • A second propensity-matched observational study included 878 consecutive COVID-19-positive patients admitted to Hartford hospital, a tertiary care hospital in Connecticut, USA (Mather 2020). In total, 83 (9.5%) patients received famotidine. These patients were somewhat younger (63.5 vs 67.5 years) but did not differ with respect to baseline demographics or pre-existing comorbidities. Use of famotidine was associated with a decreased risk of in-hospital mortality (odds ratio 0.37, 95% CI 0.16-0.86) and combined death or intubation (odds ratio 0.47, 95% CI 0.23-0.96). Patients receiving famotidine displayed lower levels of serum markers for severe disease including CRP, procalcitonin and ferritin levels. Logistic regression analysis demonstrated that famotidine was an independent predictor of both lower mortality and combined death/intubation.

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AcalabrutinibAnticomplement therapiesAzithromycinCamostatChloroquineColchicineConvalescent plasmaCorticosteroidsCytokine blockersFamotidineFavipiravirG-CSFHuman recombinant soluble ACE2HydroxychloroquineIbrutinibIloprostInterferonsJAK inhibitorsLeflunomideLopinavirMonoclonal antibodiesN-acetylcysteineOseltamivir(other) Protease inhibitors(other) RdRp inhibitorsREGN-COV2Umifenovir

Outlook | References

By Christian Hoffmann