Skip to main content
NCBI home page
Elsevier - PMC COVID-19 Collection logoLink to Elsevier - PMC COVID-19 Collection
letter
. 2022 Dec 1. Online ahead of print. doi: 10.1016/j.jinf.2022.11.022

No evidence of clinical efficacy of famotidine for the treatment of COVID-19: a systematic review and meta-analysis

Huzaifa Ahmad Cheema a,⁎, Arman Shafiee b,c, Mohammad Mobin Teymouri Athar d, Abia Shahid a, Rehmat Ullah Awan e, Ahmed M Afifi f, Jaffer Shah g, Prasun K Jalal h
PMCID: PMC9711899  PMID: 36462586

Dear Editor,

We read with great interest the recent article by Qian et al. that reported paxlovid as an efficacious treatment for COVID-19 patients.1 However, the relatively high cost of paxlovid and the other currently available oral antiviral, molnupiravir, will likely curtail their access in lower-income countries.2 , 3 Therefore, as the quest to find efficacious and cost-effective therapies for COVID-19 patients is still ongoing, repurposing drugs, that are approved for other indications, to treat COVID-19 is an attractive option. A recent trial by Brennen Christina et al.4 showed that the use of famotidine for treating mild to moderate COVID-19 patients was associated with improved recovery without any significant adverse events. However, another study by Jiandong et al.5 reported that famotidine use is associated with a higher risk of severe COVID-19 disease. Considering the newly published studies evaluating the effectiveness of famotidine and their conflicting results, we conducted a meta-analysis to determine its potential role in treating COVID-19 patients.

A systematic search was conducted on MEDLINE (via PubMed), Embase, and the Cochrane Library for relevant studies published before 15 September 2022. The inclusion criteria were comparative studies investigating famotidine for treating COVID-19 patients. Studies that used famotidine as a prophylactic agent were excluded from our analysis. The quality of the included studies was assessed using the National Institutes of Health (NIH) Quality Assessment Tool for observational cohort studies (Supplementary Table 1) and the revised Cochrane Risk of Bias Tool (RoB 2.0) for randomized controlled trials (RCTs) (Supplementary Fig. 1). The primary outcomes were all-cause mortality and the rate of no recovery. The secondary outcomes included intensive care unit (ICU) admission, time to symptom resolution, and length of hospital stay. We used RevMan 5.4 to conduct random-effects meta-analyses with odds ratios (ORs) and mean differences (MDs) as effect measures.

A total of 10 studies were included in our meta-analysis (Supplementary Table 2), of which 3 were RCTs,4 , 6 , 7 and 7 were retrospective cohort studies.8, 9, 10, 11, 12, 13, 14 Our analysis showed that famotidine has no effect on mortality (OR 0.96; 95% CI: 0.34, 2.70; I2 = 100%; Fig. 1 ); the results remained non-significant in a sensitivity analysis conducted by excluding low-quality studies (OR 0.90; 95% CI: 0.74, 1.10; I2 = 66%).9, 10, 11 In terms of time to symptom resolution, a non-significant reduction was observed in the famotidine group (MD -1.86; 95% CI: -4.08, 0.36; I2 = 81%; Fig. 2 ). Famotidine use reduced the length of hospital stay (MD -1.74; 95% CI: -2.30, -1.19; I2 = 0%; Supplementary Fig. 2) but had no effect on the number of patients with no recovery (OR 0.55; 95% CI: 0.20, 1.52; I2 = 0%; Supplementary Fig. 3) and the number of patients requiring admission to ICU (OR 1.04; 95% CI: 0.86, 1.25; I2 = 0%; Supplementary Fig. 4).

Fig. 1.

Fig 1

Open in a new tab

Effect of famotidine use on all-cause mortality in COVID-19 patients.

Fig. 2.

Fig 2

Open in a new tab

Effect of famotidine use on time to symptom resolution.

The idea of suppressing the immunological dysregulation caused by SARS-CoV-2 as a suggested treatment is evident in the literature.15 By producing histamine, prostaglandin D2 (PGD2), and leukotriene C4 (LTC4), it is believed that mast cells, stimulated by coronaviruses, were able to cause lung inflammation.16 Hence, famotidine, by virtue of its histamine H2-receptor (H2R) antagonism, may be involved in modifying the pulmonary pathogenic process.

There is a paucity of data regarding the impact of famotidine on COVID-19 patients. Only studies examining famotidine as a treatment modality were included in our review. However, it is worth noting that several studies have also reported a beneficial prophylactic effect of this drug.17 , 18 Freedberg et al. found that the initial use of famotidine in hospitalized COVID-19 patients was significantly associated with a decreased rate of intubation and death.17 These results were further corroborated by a retrospective study by Mather Jeffrey et al.18 Among the included studies in our meta-analysis, only six reported a beneficial effect of famotidine as a potential treatment.4 , 6 , 7 , 9 , 11 , 13 It is worth noting that two studies have reported increased COVID-19 severity in the group receiving famotidine5 , 10; it is likely that the highest benefit of famotidine might be seen with use early in the course of the disease.

The results of our meta-analysis for the outcome of all-cause mortality are in line with those reported by Chiu et al. and Sun et al. in their meta-analyses.19 , 20 However, these reviews only included 5 and 4 studies, respectively. Our study pooled the results from 10 studies, thereby extending the results of the previous meta-analyses with a significantly increased statistical power. Furthermore, we found that using famotidine reduced the length of hospital stay; there was also a trend towards benefit in the famotidine group for the outcomes of time to symptom resolution and the rate of no recovery. However, these estimates are based on the results of two studies each, precluding any strong conclusions, and requiring further confirmation by well-designed, large-scale RCTs which have not been conducted so far for famotidine. Another limitation of our meta-analysis is that the pooled estimates are based mostly on observational studies due to the scarcity of available RCTs; hence, they are susceptible to confounding bias.

In conclusion, famotidine is not effective in reducing mortality or increasing the rate of recovery in COVID-19 patients; hence it should not be used for this indication until large-scale RCTs have established its efficacy.

Financial support

No financial support was received for this study.

Human and animal participants

Research involving human participants and/or animals: No animals or human subjects were used in the current study.

Informed consents

No informed consents were required for the purpose of the current study.

Availability of data

The data that support the findings of this study are available from the corresponding author, HAC, upon reasonable request.

Declaration of Competing Interest

The authors report no relationships that could be construed as a conflict of interest.

Acknowledgements

Not applicable.

Footnotes

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.jinf.2022.11.022.

Appendix. Supplementary materials

mmc1.docx (494.9KB, docx)

References

  • 1.Qian Z., Pengfei M., Mingwei W., Yongran C., Mengyun Z., Lan Y., et al. Efficacy and safety of Paxlovid for COVID-19:a meta-analysis. J Infect. 2022 doi: 10.1016/j.jinf.2022.09.027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Junzheng W., Jacob L., Leah E., Andrew H. Minimum manufacturing costs, national prices, and estimated global availability of new repurposed therapies for Coronavirus Disease 2019. Open Forum Infect Dis. 2022;9(1) doi: 10.1093/ofid/ofab581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Maurish F., Saleha A., Junaid S., Abia S., Ahmad C.H. Efficacy and safety of molnupiravir for COVID-19 patients. Eur J Intern Med. 2022;102:118–121. doi: 10.1016/j.ejim.2022.05.024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Brennan Christina M., Nadella S., Xiang Z., Dima R.J., Jordan-Martin N., Demestichas B.R., et al. Oral famotidine versus placebo in non-hospitalised patients with COVID-19: a randomised, double-blind, data-intense, phase 2 clinical trial. Gut. 2022;71(5):879–888. doi: 10.1136/gutjnl-2022-326952. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Jiandong Z., Xiansong W., Sharen L., Wu W.K.K., Yung C.B.M., Qingpeng Z., et al. Proton pump inhibitor or famotidine use and severe COVID-19 disease: a propensity score-matched territory-wide study. Gut. 2021;70(10):2012–2013. doi: 10.1136/gutjnl-2020-323668. [DOI] [PubMed] [Google Scholar]
  • 6.Suraksha P., Mahesh J., Aperna D., Mehak G., Darshan L., Rakesh F.N.U., et al. Efficacy of oral famotidine in patients hospitalized with severe acute respiratory syndrome Coronavirus 2. Cureus. 2022;14(2):e22404. doi: 10.7759/cureus.22404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Reza S.H., Hassani A.M., Maryam H., Mohsen A., Dariush H., Mitra K. The efficacy of famotidine in improvement of outcomes in hospitalized COVID-19 patients: a phase III randomised clinical trial. Res Sq. 2021 doi: 10.21203/RS.3.RS-462937/V1. [DOI] [Google Scholar]
  • 8.Azza S., Patrick F.S., Rachel W., Berlin J.A., Patrick R. Comparative effectiveness of famotidine in hospitalized COVID-19 patients. Am J Gastroenterol. 2021;116(4):692–699. doi: 10.14309/ajg.0000000000001153. [DOI] [PubMed] [Google Scholar]
  • 9.Farhana S., Nazia M., Syed Mudasir Q., Suhail M., Afshan S., Tajamul H., et al. Efficacy of various treatment therapies on patient related outcome in hospitalized COVID-19 patients – a retrospective study. J Med Sci. 2022;25 doi: 10.33883/jms.v25i2.1177. Ski. 2 SE-Original Articles. [DOI] [Google Scholar]
  • 10.Eugene S., Bara E.K., Allison H., Sylvia K., Saatchi K., Aziz T., et al. S1301 a retrospective review: famotidine use is not associated with improved outcomes in hospitalized patients with COVID-19. Am J Gastroenterol. 2021;116(1):S598. doi: 10.14309/01.ajg.0000778736.01714.cd. -S598. [DOI] [Google Scholar]
  • 11.Justin W., Aaron D., Nikolas S.C., Joshua F., John T. S1458 famotidine versus pantoprazole use and clinical outcomes in patients hospitalized with COVID-19: a retrospective study. Am J Gastroenterol. 2021;116(1):S668–S669. doi: 10.14309/01.ajg.0000779364.64867.ec. [DOI] [Google Scholar]
  • 12.Samrat Y., Pratik D., Kenneth S., Mandelin C., Dax K., Gregg F. Famotidine use is not associated with 30-day mortality: a coarsened exact match study in 7158 hospitalized patients with Coronavirus Disease 2019 from a large healthcare system. Gastroenterology. 2021;160(3):919–921. doi: 10.1053/j.gastro.2020.10.011. e3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Cameron M., Saskia P., Susanne N., Max H., Bourne P.E., Robert P. Real-world evidence for improved outcomes with histamine antagonists and aspirin in 22,560 COVID-19 patients. Signal Transduct Target Ther. 2021;6(1):267. doi: 10.1038/s41392-021-00689-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Toshiki K., Matsuo S., Mai T., Egorova N.N. The association between famotidine and in-hospital mortality of patients with COVID-19. J Med Virol. 2022;94(3):1186–1189. doi: 10.1002/jmv.27375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15.Fatemeh A., Arman S., Sayeh R., Zakiye M., Mahshid S., Somayeh Y., et al. Comparative study of CNR1 and CNR2 cannabinoid receptors expression levels in COVID-19 patients with and without diabetes mellitus: recommendations for future research targets. Diabetes Metab Syndr Clin Res Rev. 2022;16(5) doi: 10.1016/j.dsx.2022.102499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Kritas S.K., Ronconi G., Caraffa A., Gallenga C.E., Ross R., Conti P. Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy. J Biol Regul Homeost Agents. 2020;34(1):9–14. doi: 10.23812/20-Editorial-Kritas. [DOI] [PubMed] [Google Scholar]
  • 17.Freedberg D.E., Conigliaro J., Wang T.C., Tracey K.J., Callahan M.V., Abrams J.A., 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. doi: 10.1053/j.gastro.2020.05.053. e3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Mather Jeffrey F., Seip Richard L., McKay Raymond G. Impact of famotidine use on clinical outcomes of hospitalized patients with COVID-19. Am J Gastroenterol. 2020;115(10):1617–1623. doi: 10.14309/ajg.0000000000000832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Leonard C., Max S., Chun-Han L., Nicholas C., Austin C., Joon S.H., et al. Effect of famotidine on hospitalized patients with COVID-19: a systematic review and meta-analysis. PLoS One. 2021;16(11) doi: 10.1371/journal.pone.0259514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Chenyu S., Yue C., Lei H., Yile W., Mingming L., Ahmed Mubashir A., et al. Does famotidine reduce the risk of progression to severe disease, death, and intubation for COVID-19 patients? A systemic review and meta-analysis. Dig Dis Sci. 2021;66(11):3929–3937. doi: 10.1007/s10620-021-06872-z. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

mmc1.docx (494.9KB, docx)

Data Availability Statement

The data that support the findings of this study are available from the corresponding author, HAC, upon reasonable request.

Articles from The Journal of Infection are provided here courtesy of Elsevier

RESOURCES