Repurpusing Famotidine against COVID-19: a Hope or a Hype?

Clinicians and scientists have been studying a number of old existing drugs with the hope of finding therapies they can repurpose to fight COVID-19. A good example of this is Gilead Sciences’ Remdesivir directly go after the virus SARS-CoV-2, which causes the disease.

Recently, one of the most common histamine-H2-receptor antagonist, famotidine the ingredient in the over-the-counter heartburn drug Pepcid that was found to provide benefits for COVID-19 patients. Famotidin works by preventing stomach acid production. However, if  it would have any activity in an infectious disease is a bit strange assumption. Clinicians first became interested in famotidine after hearing reports, that people in China who took the drug for heartburn were surviving COVID-19, while other people who essentially had the same risk factors but were taking different heartburn drugs like cimetidine or omeprazole (sold as Tagamet and Prilosec) were dying from the disease.

Why Famotidine?

In early April, doctors began a clinical trial at New York’s Northwell hospitals to test famotidine’s efficacy. They reasoned that even if evidence for famotidine’s effectiveness was largely anecdotal, the drug has been around for over 30 years and has a good safety profile.

So, if it worked, it would be a fast and cheap way to ease the symptoms of COVID-19.

In Northwell hospitals high doses of intravenous famotidine were administered. Their goal was to enroll 1.200 people with moderate to severe COVID-19 and see if those that got famotidine were less likely to die or require a ventilator. Then, in late April, the first data were reported in Science Magazine.

As a consequence of this report, no wonder that boxes of Pepcid began to fly off of pharmacy shelves as people sought out any potential remedy during the pandemic.

Shortly afterward, on May 8, a team, led by Columbia University doctors Daniel Freedberg and Julian Abrams, posted a study on the preprint server medRxiv that compared the outcomes of people with COVID-19 who were prescribed famotidine within 24 hours of being admitted to the hospital to those who did not get the heartburn drug. They looked at the records of more than 1.600 patients at Columbia University Irving Medical Center between late February and middle of April. Of those, 84 patients received 10–40 mg of intravenous famotidine daily over the course of about 6 days. The patients who got famotidine fared better. According to the study, they were far less likely to die or require a ventilator—a two-fold decrease in risk—than those not receiving the drug. The results were published in the Gastroenterology later in May.

Even though the results were promising, doctors concluded that further studies are required to support their observations: “This is merely an association, and these findings should not be interpreted to mean that famotidine improves outcomes in patients hospitalized with COVID-19,” the team says in a statement. “It is also not clear why those patients who received famotidine had improved outcomes.”

For clarity on famotidine’s effectiveness, the team recommends to wait for the outcome of the trial going on at Northwell hospitals. “Hopefully the results from this trial will determine whether famotidine is efficacious for the treatment of COVID-19,” the team says in its statement. Meanwhile, in early June, the journal Gut published a small case series of 10 people who developed COVID-19 and reported taking famotidine during their illness.

These people were not sick enough to get hospitalized, but their symptoms, such as cough and shortness of breath, improved within a day or two of taking the heartburn drug. It was a small study, and the researchers acknowledge that it is not enough to establish that there is any real benefit from taking famotidine for people who have COVID-19. Those authors recommend a clinical trial with famotidine be carried out with patients with milder disease in addition to the trial going on at Northwell hospitals.

The team’s tests showed that famotidine has no effect on SARS-CoV-2’s papain-like protease, nor does it kill the virus. Instead, researchers think the famotidine is working through its usual target—histamine H2 receptors. This drug treats heartburn by blocking H2 receptors, which when activated by histamine, will stimulate cells in the stomach to secrete acid.