Early in the Covid pandemic, Chinese physicians noted that indigent patients who used a less expensive medication called famotidine (Pepcid) to treat heartburn and acid reflux fared better when treated for Covid-19 than wealthier patients who used more expensive prescription proton-pump inhibitors (PPIs).
Famotidine, an over-the-counter histamine-2 blocker, competes with proton-pump inhibitors (PPIs) that are among the world’s most widely used medications. PPIs include medications like Nexium (esomeprazole), Prilosec (omeprazole), Prevacid (lansoprazole), and a dozen other names. Both classes of drugs efficiently fight heartburn and Barrett’s esophagitis by lowering gastric acid production in the stomach.
However, gastric acid kills Covid-19 in the stomach. Gastric acid normally protects intestinal cells by keeping the stomach’s pH at an acidic level of about 3.0 that kills viruses and other pathogens.
When someone takes a PPI medication to block gastric acid release for heartburn, acid reflux, or stomach ulcers, they will feel better. However, they are also lowering the stomach’s gastric acid level that allows more Covid-19 to access and infect intestinal cells.
PPIs can reduce the stomach’s acidity to such a degree that more Covid-19 viruses pass through the stomach to reach a prime target, intestinal cells. Like lung cells, intestinal cells have multiple ACE-2 enzyme receptors on their outer wall. Covid prefers ACE-2 receptors for cell entry and death. In a Korean study, the use of PPIs nearly doubled Covid’s severity. In a survey of over 53,000 people in the U.S., researchers found the risk of getting Covid was 2.1 and 3.7 times higher in those who took a PPI once or twice a day, respectively.
Famotidine (Pepcid) Appears Protective
During a pandemic, anyone at risk might consider switching to famotidine because it does not reduce gastric acidity to the same degree as a PPI. Even better, famotidine offers another important protection: it reduces Covid-19’s ability to multiply after breaking into human cells. Early computer models of existing medications placed famotidine among the top-of-the-list candidates to be tested against Covid-19. Famotidine blocks the 3-chymotrypsin-like protease enzyme on the cell’s interior that enables Covid-19 to make multiple copies of itself once it enters human cells.
Of 1,620 patients admitted to a Columbia University Irving Medical Center with Covid-19, 84 had received famotidine after being admitted. Only 13 of the 84 were taking famotidine before admission. All 84 received it after admission, with 28% getting it through an IV and the rest orally. Doses averaged just over 20 mg per day for six days. Those who got famotidine had a 57% lower risk for death or intubation.
Researchers in New York followed ten non-hospitalized patients with Covid who had previously started themselves on high famotidine doses after their diagnosis. Most used 80 mg of famotidine three times a day for about 11 days. Nine of the ten started famotidine within four days of symptom onset, and one person started on day 26. The researchers evaluated five Covid symptoms of cough, shortness of breath, fatigue, headaches, and anosmia or loss of smell, along with general unwellness, ranked on a four-point scale.
All ten patients reported a marked improvement in their symptoms after starting famotidine with cough and shortness of breath reported to improve more rapidly than fatigue. Three patients reported famotidine side-effects during treatment. One had mild dizziness and an occasional racing heartbeat. Another had mild dizziness and insomnia, and the third had mild GI symptoms and temporary forgetfulness.
Other researchers followed 878 consecutive patients admitted to a Connecticut hospital, of whom 83 (9.5%) had taken some famotidine within seven days before or after hospital admission. Of these 83 patients, two-thirds started famotidine after being admitted and generally took 80 mg a day for four days.
After compensating for other factors, the use of famotidine was associated with a 61% lower risk of dying in the hospital. The famotidine group had a 14.5% death rate and 21.7% required intubation. This compares to a 26% death rate and 32.1% intubation rate in the non-famotidine group. Among people requiring intubation, the death rate was 7.2% for those who got famotidine compared to 13.8% for the non-famotidine group. The famotidine group also had lower inflammatory C-reactive protein (p = 0.002) and procalcitonin (p = 0.004) that suggests a blood infection.
The authors stated, “Famotidine use in hospitalized patients with Covid-19 is associated with a lower risk of mortality, lower risk of combined outcome of mortality and intubation, and lower levels of serum markers for severe disease.” They recommended the conduction of randomized controlled trials to verify their findings.
Proton-pump Inhibitors May Worsen Outcomes
Out of over 130,000 Korean adults who tested positive for Covid-19, more than 14,000 of them were on a proton-pump inhibitor (PPI) for gastric acid suppression. Within 30 days before hospital admission, taking a PPI medication was associated with nearly a doubling in the risk for a severe outcome from Covid-19.
Of 53,130 participants in an online survey in May and June 2020, 6.4% of those responding reported a positive Covid-19 test. In an analysis conducted by the researchers, people using PPIs up to once a day were 2.1 times more likely to report having a positive Covid-19 test. Those taking a PPI twice a day were 3.7 times more likely to report testing positive than those who had not taken a PPI. Additionally, the researchers found that the patients taking histamine-2 receptor antagonists (H2RAs) were not at an increased risk to test positive for Covid-19.
How much famotidine is a good dose to take? For adults at risk for Covid, a 20 mg tablet of famotidine once a day may provide initial protection even without an intestinal problem. If active Covid symptoms begin, higher famotidine doses of 40 to 60 mg taken three times a day appear to reduce both the severity and mortality of Covid-19.
Stopping a PPI must be done carefully. Discuss stopping a PPI with your physician before you do anything. Suppose you have been on a PPI for more than a couple of months. In that case, it is usually better to reduce the PPI dose gradually over time to avoid a rebound in gastric acid secretion. Famotidine taken once or twice a day can be a reasonable replacement for a PPI during the pandemic.