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Famotidine (Pepcid) and COVID-19
Question: I read that famotidine (Pepcid) may help treat COVID-19. Is this true? Are there risks with taking famotidine?
Answer: Interest in famotidine as a treatment for COVID-19 (caused by the coronavirus SARS-CoV-2) was triggered by a preliminary report that people in China with COVID-19 who had taken famotidine for its approved use (as an "H2 blocker" to reduce stomach acidity) had better outcomes than people who were not taking it or who had been using other types of acid reducers, such as Prilosec (omeprazole — a proton pump inhibitor).
The evidence regarding famotidine and COVID-19:
An article in Science (April 26, 2020) that discusses the findings from China stated: "In reviewing 6212 COVID-19 patient records, the doctors noticed that many survivors had been suffering from chronic heartburn and were on famotidine rather than more-expensive omeprazole (Prilosec), which is a proton pump inhibitor and the medicine of choice both in the United States and among wealthier Chinese. Hospitalized COVID-19 patients on famotidine appeared to be dying at a rate of about 14% compared with 27% for those not on the drug, although the analysis was crude and the result was not statistically significant." The article also notes anecdotal reports in the U.S. of a women who recovered from symptoms of COVID-19 the day after taking a "megadose" of oral famotidine and of "dramatic improvements" in five other sick people (three confirmed for COVID-19) after taking oral famotidine.
A review of the records of 1,620 COVID-19 patients (none of whom required immediate mechanical ventilation) admitted to Columbia University hospital in New York showed that those who had received famotidine (intravenous or oral, to suppress gastric acid) within 24 hours of admission were 70% less likely to have died within 30 days of admission. There was no association between famotidine and the need for intubation (being put on a ventilator). Interestingly, use of proton pump inhibitors, which also suppress gastric acid, was not associated with reduced risk for death or intubation. Among the patients who had received famotidine, 72% had received it orally (10 to 40 mg daily) and 28% intravenously (dose not reported) (Freedberg, medRxiv 2020 -- preprint).
A possible mechanism by which famotidine may work is by inhibiting an enzyme (3-chymotrypsin-like protease or 3CLpro) essential for processing proteins needed for viral replication, according to computational modeling (Wu, Acta Pharm Sin B 2020).
A clinical trial in New York began in April of 2020 in which famotidine is being given intravenously in very large doses to patients hospitalized with COVID-19. Patients receive three intravenous doses daily, each providing 120 mg of famotidine, i.e., 360 mg total per day. (Note: A normal oral daily dose of famotidine for heartburn is 10 to 20 mg up to twice daily.) The study is to be completed in September.
Until results of this or other trials with famotidine are published, there is no solid evidence that famotidine is effective in treating COVID-19, and there is not even anecdotal evidence that it prevents SARS-CoV-2 infection.
Be aware of risks with famotidine:
Side effects that have been reported with famotidine at a dose of 40 mg at bedtime (taken to treat acute gastrointestinal ulcers) are headache (4.7%), dizziness (1.3%), constipation (1.2%), and diarrhea (1.7%)(Pepcid insert, Drugs@FDA). The study in New York excluded COVID-19 patients with decreased kidney function because high doses of famotidine can cause heart problems in them. Other adverse effects that have been infrequently reported with famotidine use include including jaundice and anorexia; rare cases of blood abnormalities; musculoskeletal pain; seizures; psychiatric disturbances; respiratory reactions (bronchospasm and interstitial pneumonia); various skin effects maladies including, very rarely, epidermal necrosis; tinnitus; and taste disorder. In addition, famotidine should not be used by anyone with an allergy to famotidine or other acid reducers.
Long-term use of famotidine and other medications that lower stomach acidity has been associated with deficiency in vitamin B12 and zinc, possibly due to poorer extraction of these nutrients from foods. Supplementation with these may be advisable with long-term use of famotidine. When discontinuing famotidine, a rebound in gastric acid production can potentially occur, causing abdominal discomfort. To help avoid this, do not stop abruptly, but taper the dose down over several days.
Also be aware that some over-the-counter formulations of famotidine include substantial amounts of other active ingredients. Pepcid Complete, for example, provides a modest amount of famotidine (10 mg) along with 320 mg of calcium and 70 mg of magnesium per tablet, and no more than two should be taken per day. Excessive intakes of calcium or magnesium from supplements are not advisable.