Tecta, PPIs and COVID-19: what the evidence shows and how CYP2C19 can guide your dose

Proton pump inhibitors (PPIs), such as pantoprazole (Tecta, Pantoloc), omeprazole (Losec), esomeprazole (Nexium), lansoprazole (Prevacid), rabeprazole (Pariet) and dexlansoprazole (Dexilant), are among the most commonly used medications in Canada. Early in the pandemic, a study suggested that people taking PPIs were more likely to get COVID-19. This article explains what that study found, what larger studies showed afterwards, which long-term PPI risks are well established, and how a pharmacogenetic test can help your prescriber find the right PPI dose.

What are PPIs and why do people take them?

PPIs reduce the amount of acid the stomach makes. They are used to treat heartburn and gastroesophageal reflux disease (GERD), to heal and prevent stomach and duodenal ulcers, including ulcers caused by anti-inflammatory medications, and, together with antibiotics, to treat Helicobacter pylori infection. They work well and are generally safe, but many people take them for longer, or at higher doses, than they need. Read more about how genetics affects the effectiveness of Tecta.

Do PPIs increase the risk of COVID-19?

Stomach acid helps protect against bacteria and viruses that are swallowed, so researchers asked whether lowering it might make it easier for the COVID-19 virus to infect the gut.

• The early survey. In an online survey of 53,130 American adults in May and June 2020, 3,386 reported a positive COVID-19 test. People taking a PPI up to once a day had about twice the odds of reporting a positive test, and those taking a PPI twice a day had 3.7 times the odds, compared with people not taking PPIs. People taking the weaker acid reducers called H2 blockers, such as famotidine, did not have higher odds. Because the study relied on self-reported results, it could show an association but not prove cause and effect.
• A national Korean study. Among 132,316 people tested for COVID-19, taking a PPI was not linked to a higher chance of testing positive. Among those who were infected, current PPI users had more severe outcomes.
• A national Danish study. Among all 83,224 COVID-19 cases in Denmark, PPI use was linked to only a very small increase in the risk of infection, which the authors considered most likely due to other differences between PPI users and non-users. PPI use was not linked to severe outcomes, and an updated meta-analysis found no effect on the risk of infection or death.
• A meta-analysis of 15 studies. PPI use was not linked to getting COVID-19, but was linked to more severe illness among those infected, with the caution that the studies varied widely and that people who take PPIs often have other health problems.

Overall, the evidence does not show that PPIs meaningfully increase the risk of catching COVID-19. Whether they make COVID-19 more severe remains uncertain. Do not stop a PPI on your own because of COVID-19, but it is reasonable to ask your doctor or pharmacist whether you still need it and whether you are taking the lowest dose that works.

What are the long-term risks of PPIs?

Many risks of long-term PPI use, such as fractures, kidney disease and dementia, come from observational studies that cannot rule out other explanations. The strongest evidence comes from a large randomized trial in which 17,598 people with heart or blood vessel disease took pantoprazole 40 mg a day or a placebo for about three years. Pantoprazole did not increase most of the risks that had been suspected, with one exception: enteric (gut) infections were about 33% more common, 1.4% compared with 1.0%. Long-term PPI use can also lower vitamin B12 and magnesium levels, which your doctor may check.

These findings support a simple principle: take a PPI only when it is needed, at the lowest dose that controls your symptoms.

How do genes affect the dose of Tecta and other PPIs?

Omeprazole, lansoprazole and pantoprazole (Tecta) are broken down mainly by the liver enzyme CYP2C19, which handles about 80% of their clearance. Variations in the CYP2C19 gene change how much medication stays in your body. Guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC) recommend:

• Ultrarapid metabolizers: clear these PPIs quickly and may not get enough acid suppression. CPIC recommends starting at double the standard daily dose.
• Rapid metabolizers: start at the standard dose; a 50% to 100% higher dose can be considered for H. pylori infection and erosive esophagitis.
• Normal metabolizers: start at the standard dose; a 50% to 100% higher dose can be considered for H. pylori infection and erosive esophagitis.
• Intermediate and poor metabolizers: have 3 to 14 times higher PPI levels. Start at the standard dose, which is likely to work well, and for long-term use beyond 12 weeks, consider reducing the daily dose by half once symptoms are controlled, to lower the risk of side effects.

The same recommendations apply to dexlansoprazole. Esomeprazole and rabeprazole depend less on CYP2C19, and CPIC does not make recommendations for them. Other medications matter too: strong inhibitors of CYP2C19 or CYP3A4 can raise PPI levels, and inducers such as rifampin can lower them. See the CPIC guidelines on ClinPGx.

How can a Pillcheck test help?

With Pillcheck, a pharmacist reviews your CYP2C19 results together with all of your current medications, accounts for drug-drug-gene interactions and prepares recommendations that you can share with your doctor, for example whether a lower long-term PPI dose may be enough for you, or whether a higher dose or a different PPI may work better. The same test also covers many other medications that people taking PPIs often use, such as antidepressants, blood thinners and pain medications.

Pillcheck testing is performed in CAP- and COLA-accredited clinical genetic laboratories located in Canada. Pillcheck reports on 24 genes, increasing coverage with new guidelines and drug labels (see the genes tab), and covers 355 medications, which account for over 70% of dispensed prescriptions. The Pillcheck test panel ensures high accuracy for people of non-European and admixed ancestries. Your results last a lifetime, and report updates are free of charge.

Summary

• An early 2020 survey linked PPI use to higher odds of reporting a positive COVID-19 test, but larger national studies and meta-analyses did not confirm a meaningful increase in infection risk.
• Whether PPIs affect COVID-19 severity remains uncertain.
• In a large randomized trial, long-term pantoprazole was safe apart from a modest increase in gut infections.
• PPIs should be used only when needed, at the lowest effective dose.
• CYP2C19 genotype guides the dose of pantoprazole (Tecta), omeprazole, lansoprazole and dexlansoprazole, according to CPIC guidelines.

Frequently asked questions

Should I stop taking Tecta because of COVID-19?

No, not on your own. The evidence does not show that PPIs meaningfully raise the risk of catching COVID-19. Ask your doctor or pharmacist whether you still need a PPI and whether a lower dose would work.

Why does my PPI not control my heartburn?

There can be many reasons, including timing (PPIs work best taken 30 to 60 minutes before a meal) and the cause of your symptoms. People who are CYP2C19 rapid or ultrarapid metabolizers clear pantoprazole, omeprazole and lansoprazole faster and may need a higher dose.

Is esomeprazole affected by my genes?

Less than other PPIs. Esomeprazole and rabeprazole depend less on CYP2C19, and CPIC does not make genotype-based recommendations for them.

References

Almario CV, Chey WD, Spiegel BMR. Increased risk of COVID-19 among users of proton pump inhibitors. Am J Gastroenterol. 2020;115(10):1707-1715.

Lee SW, Ha EK, Yeniova AÖ, et al. Severe clinical outcomes of COVID-19 associated with proton pump inhibitors: a nationwide cohort study with propensity score matching. Gut. 2021;70(1):76-84.

Israelsen SB, Ernst MT, Lundh A, et al. Proton pump inhibitor use is not strongly associated with SARS-CoV-2 related outcomes: a nationwide study and meta-analysis. Clin Gastroenterol Hepatol. 2021;19(9):1845-1854.e6.

Kim HB, Kim JH, Wolf BJ. Acid suppressant use in association with incidence and severe outcomes of COVID-19: a systematic review and meta-analysis. Eur J Clin Pharmacol. 2022;78(3):383-391.

Moayyedi P, Eikelboom JW, Bosch J, et al. Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin. Gastroenterology. 2019;157(3):682-691.e2.

Ito T, Jensen RT. Association of long-term proton pump inhibitor therapy with bone fractures and effects on absorption of calcium, vitamin B12, iron, and magnesium. Curr Gastroenterol Rep. 2010;12(6):448-457.

Lima JJ, Thomas CD, Barbarino J, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C19 and proton pump inhibitor dosing. Clin Pharmacol Ther. 2021;109(6):1417-1423.