Treating Acid Reflux With Over-the-Counter Medications

Acid reflux is a symptom of gastroesophageal reflux (GER) or gastroesophageal reflux disease (GERD). It happens when the contents of the stomach travel back up into the esophagus. GERD may develop if the lower esophageal sphincter is weak or relaxes when it should not.¹ Acid reflux can be uncomfortable with symptoms including heartburn and regurgitation, which can be aggravated by trigger foods, commonly including alcohol, carbonated beverages, chocolate, citrus, caffeine, fried and fatty foods, as well as spicy foods.²

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What options are available and how do we decide?

When asked for a recommendation for acid reflux, pharmacists should first obtain some background information and provide education. Ask about the patient’s symptoms, lifestyle, diet, and past medical history.³

There are many diet and lifestyle changes that may alleviate symptoms of heartburn and regurgitation. Recommendations may include weight loss, tobacco cessation, elevation of the head of the bed, avoiding lying down after eating, and avoidance of trigger foods. If a patient is unsure of their trigger foods, a journal may be helpful in determining this.³

There are many over-the-counter (OTC) options that can be recommended for symptoms of GERD. These medications are targeted at neutralization or reduction of gastric acid including histamine H2-receptor antagonists (H2RA), proton pump inhibitors (PPI), and antacids.³

For infrequent heartburn, many patients will try antacids prior to seeking medical attention.⁴ Common OTC antacids include calcium carbonate (eg, Rolaids, Tums, Mylanta).⁵ If the patient is not finding relief from antacids, OTC H2RAs including cimetidine (Tagamet) and famotidine (Pepcid) may provide additional relief and acid-suppression. Famotidine is available OTC in 10 mg and 20 mg strengths, with dosing of 10 to 20 mg up to twice daily as needed with a maximum daily dose of 40 mg. If symptoms persist or occur more than twice a week with twice daily dosing of famotidine, a PPI would be recommended.⁶

Before recommending a PPI, it is important to ensure that no alarm symptoms are present which would require a referral. Alarm symptoms include:

1. dysphagia,
2. odynophagia,
3. bleeding,
4. weight loss

If these symptoms are absent, a 2-week trial period of PPIs once daily before a meal is recommended for patients experiencing frequent heartburn, defined as occurring 2 or more days a week.⁴ Common OTC options include lansoprazole (Prevacid; Takeda Pharmaceuticals USA, Inc), esomeprazole (Nexium; Pfizer), and omeprazole (Prilosec; Procter & Gamble). These medications are not intended for immediate relief, and it is important to inform the patient that it may take a few days to see the full effect. OTC PPI therapy should not exceed 14 days or be used more than 3 times per year, without additional assessment from a health care provider.⁵

When to refer patients

If a patient reports symptoms of acid reflux or GERD, they should be assessed for any of the alarm symptoms discussed previously. If these symptoms are present, they should be referred to a health care provider to confirm a diagnosis and check for complications. If GERD symptoms are not controlled with lifestyle modifications, if symptoms become severe or persistent, or if OTC medications are needed for over 2 weeks, the patient should be referred to another health care provider for additional assessments and screenings.⁷ Special populations that should be referred to another provider include pregnant women with moderate or frequent heartburn, children under 18 prior to using a PPI and children under 12 prior to using a H2RA or antacid.^8,9

Potential risks of prolonged use of PPIs

PPIs are commonly used with nearly 100 million annual prescriptions dispensed.10 With OTC availability, patients may use these drugs for extended periods of time. Long-term PPI adverse effects include vitamin malabsorption, clostridium difficile associated disease (CDAD), community-acquired pneumonia (CAP), and chronic kidney disease (CKD).

Vitamin Malabsorption

Vitamin B12

An acidic environment is necessary for vitamin B12 to be digested and absorbed.Via gastric acid, proteins found in food release vitamin B12 which is broken down and absorbed. Since PPIs decrease the amount of gastric acid in the stomach, vitamin B12 is less likely to be released and absorbed into the blood.¹¹ A 2013 study evaluated 184,199 patients with no prior vitamin B12 deficiency and found that a 2 or more years supply of a PPI led to an increased risk of B12 deficiency.¹²

Calcium

Ninety-nine percent of calcium is found in the bone, and like vitamin B12, calcium needs an acidic environment to be absorbed. PPIs cause malabsorption of calcium resulting in decreased osteoclasts and osteoblasts, inhibiting bone formation and increasing the risk of fractures.¹³

Magnesium

PPIs have been associated with hypomagnesemia since 2006 through decreased activity of magnesium’s main transporter, whose activity is increased in acidic environments.¹⁴ In one study, 2 patients who had been on PPI therapy and were experiencing symptoms of hypomagnesemia were given high-dose magnesium supplementation. As soon as the PPI was discontinued, their magnesium levels rapidly rose to the normal range. When put on an H2RA, their magnesium levels remained normal without supplementation.¹⁵

Infections and CKD

Clostridium difficile Associated Disease

PPIs may also lead to infections including CDAD and CAP. Though it has been determined that PPIs do not affect the pH of the colon directly, these medications cause an increase of CDAD taxa in the stool. In a 2015 study, 12 healthy individuals took a course of PPI therapy for 8 to 12 weeks. It was found that the course of therapy increased Enterococcaceae and Streptococcaceae and decreased Clostridiale (which are associated with CDAD) in stool samples of these patients after therapy was completed.¹⁶

Community-Acquired Pneumonia

PPIs have also been associated with an increased incidence of CAP. The stomach’s low pH protects against pathogens, therefore the increased pH caused by PPIs increases the survival of bacteria. In a 2012 study including 463 patients, a larger amount of oropharyngeal flora found in CAP was seen in patients taking a PPI. It was also determined that patients taking a PPI had 2.23 times greater risk of developing Streptococcus pneumoniae.¹⁷

CKD

Studies from 2016 also suggest that PPI use increases the risk of CKD. In one of the studies containing a sample size of 10,482 patients with an average age of 63 years old, a 50% increased risk of CKD was seen in 12 to 15 years of PPI use.¹⁸

How to taper off of PPIs

Though PPIs have risks, patients indicating long-term PPI use, such as complicated GERD, Barrett esophagus, chronic NSAID therapy, or history of a GI bleed secondary to an ulcer, should continue on PPIs. However, patients who have been on a PPI for 4 weeks or more and whose symptoms are no longer present, whose risks outweigh the benefits, or who have no indication, should wean off PPIs over 2 to 4 weeks.¹⁵ Patients who have been taking the PPI twice daily should transition to once daily or alternate days from once-daily therapy. H2RAs or antacids may be considered if the patient experiences acid-reflux symptoms during their tapering.¹⁹

Patients on PPIs for erosive esophagitis may see a recurrence of symptoms after withdrawal of treatment and may not find it beneficial to stop therapy. Similarly, the risks may outweigh the benefits when it comes to deprescribing PPIs in patients with eosinophilic esophagitis. Patients should monitor for formation of fibrotic strictures and inflammation when weaning off therapy. Deprescribing prolonged PPI therapy commonly results in rebound acid hypersecretion. When PPIs are discontinued and are no longer keeping gastric pH low, gastric acid secretion increases and results in upper GI symptoms, as seen in a 2009 study.²⁰ To control these symptoms, H2RAs and as-needed antacids may be considered for use.

REFERENCES

1. National Institute of Diabetes and Digestive and Kidney Diseases. Acid Reflux (GER & GERD) in Adults. July 2022. Accessed July 5, 2024. https://www.niddk.nih.gov/health-information/digestive-diseases/acid-reflux-ger-gerd-adults

2. Kassim O. GERD Triggers: What’s Turning the Heat Up on Your Heartburn? Loyola Medicine. November 17, 2021. Accessed July 5, 2024. https://www.loyolamedicine.org/about-us/blog/gerd-triggers-and-heartburn

3. Katz PO, Dunbar KB, Schnoll-Sussman FH, Greer KB, Yadlapati R, Spechler SJ. ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease. Am J Gastroenterol. 2022;117(1):27-56. doi:10.14309/ajg.0000000000001538

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6. Famotidine (Lexi-Drugs). Lexicomp Online. Published June 28, 2024. Accessed July 5, 2024. https://online./lexi.com.

7. American College of Gastroenterology. Acid Reflux / GERD (gastroesophageal reflux disease). Accessed July 9, 2024. https://gi.org/topics/acid-reflux/#tabs5

8. Sison G. How to Counsel Patients on Heartburn Treatment. Single Care Blog. November 3, 2022. Accessed July 16, 2024. https://www.singlecare.com/blog/pharmacist-counseling-for-heartburn/

9. DailyMed. National Institutes of Health. Accessed July 16, 2024. https://dailymed.nlm.nih.gov/dailymed/

10. Lehault, W. B., & Hughes, D. M. (2017, February). Review of the long-term effects of proton pump inhibitors. Federal practitioner : for the health care professionals of the VA, DoD, and PHS. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372031/#b1-fp-34-02-19

11. Tefferi A, Pruthi RK. The biochemical basis of cobalamin deficiency. Mayo Clin Proc. 1994;69(2):181–186.

12. Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-2442. doi:10.1001/jama.2013.280490

13. Flynn A. The role of dietary calcium in bone health. Proc Nutr Soc. 2003;62(4):851–858.

14. William JH, Danziger J. Proton-pump inhibitor-induced hypomagnesemia: current research and proposed mechanisms. World J Nephrol. 2016;5(2):152–157.

15. Fatuzzo P, Portale G, Scollo V, Zanoli L, Granata A. Proton pump inhibitors and symptomatic hypomagnesemic hypoparathyroidism. J Nephrol. 2017;30(2):297-301. doi:10.1007/s40620-016-0319-0

16. Freedberg DE, Toussaint NC, Chen SP, et al. Proton Pump Inhibitors Alter Specific Taxa in the Human Gastrointestinal Microbiome: A Crossover Trial. Gastroenterology. 2015;149(4):883-5.e9. doi:10.1053/j.gastro.2015.06.043

17. de Jagar CP, Wever PC, Gemen EF, et al. Proton pump inhibitor therapy predisposes to community-acquired Streptococcus pneumoniae pneumonia. Aliment Pharmacol Ther. 2012;36(10):941–949.

18. Farrell B, Pottie K, Thompson W, et al. Deprescribing proton pump inhibitors: evidence-based clinical practice guideline. Can Fam Physician 2017;63:354–64.

19. Kim J, Blackett JW, Jodorkovsky D. Strategies for effective discontinuation of proton pump inhibitors. Curr Gastroenterol Rep 2018;20:27. http://dx.doi.org/10.1007/s11894-018-0632-y

20. Reimer C, Søndergaard B, Hilsted L, Bytzer P. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology. 2009;137(1):80-87.e1. doi:10.1053/j.gastro.2009.03.058