Are OTC Proton Pump Inhibitors a Boon Or a Curse?

Proton pump inhibitors(PPIs) are the mainstay therapy for health conditions such as gastro-esophageal reflux disease (GERD), caused by reflux of excessive gastric acid production into the esophagus. In addition to PPIs’ role as treatment of choice for GERD, they are also used clinically for the management of Barrett’s esophagus, Helicobacter pylori infections (in conjunction with antibiotics), peptic ulcers (which are predominantly the by-product of excessive use of nonsteroidal anti-inflammatory drugs), and for Zollinger–Ellison syndrome, among others.

Pantoprazole, omeprazole, lansoprazole, esomeprazole, rabeprazole, and dexlansoprqzole are examples of prescription PPIs that are currently in clinical use in the US. Of these 6 most commonly used PPIs, omeprazole, esomeprazole, and lansoprazole are also available to patients as OTC products. Since the first clinical use approval by the FDA in 1989 (for omeprazole),¹ there has been an upward—and frequently clinically unjustified—trend in prescribing habits. Consequently, there is an uptick in excessive and long-term use of PPIs by a larger percentage of the US population. Additionally, since their introduction as an OTC product in 2003, many patients started to use PPIs without any real and medically justifiable reasons, and without clinical supervision.

In the late 1990s, approximately 4% of US patients were on prescription-based PPIs. In contrast, since their approval as OTC products, use of prescription-based PPIs has almost quadrupled. There is also a direct correlation between increased PPI prescribing trends and the number of published research reporting adverse effects of PPI overuse.² On average, about 7% to 15% of the total US patient population, irrespective of their age and gender, use PPIs at any given time.^2,3 Based on a cross-sectional study of approximately 6.8 billion outpatient visits between 2009 and 2015, about 600 million patients (or 8.8% of total study population) were also using prescription PPIs.³ Surprisingly, nearly two-thirds of these patients were on PPIs with no clear health care outcomes goals and for an undecided and unjustified duration of treatment. And about 25% of older adults in the US use prescription PPIs for a long term (> 1 year) on a daily basis. Many of these patients also buy OTC PPI products on a regular basis.⁴

This unintentional overuse of OTC PPIs can be attributed, in part, to patients’ limited exposure to biomedical and pharmaceutical sciences education, and ignorance about medical/pharmaceutical terminology. Most the patients purchasing OTC PPIs are unaware that they do not offer immediate relief from the acidity (or heartburn) problem, and it could be a minimum of 1 to 4 days before exhibiting any observable therapeutic benefits.⁵ This completely rules out the main objective patients typically have, i.e. immediate relief from heartburn.

Additionally, PPIs should not be used unless patients are experiencing 2 days per week or more of heartburn.⁶ Ignorance to these clinical features pertaining to PPI rationale use frequently and potentially leads to therapeutic duplication in patients who also happen to be on prescription PPIs. There are multiple research studies, systematic reviews, national gastroenterology bodies recommendations, and FDA warnings highlighting the increased risk of health care concerns such as kidney problems,³ bone fracture risk (especially in the hip, wrist and spine bones),⁶ increased chronic kidney disease,⁷ increased infection susceptibility (especially antibiotic-resistant Clostridium difficile),⁸ and cardiovascular diseases.⁹ Use of OTC PPIs is unjustified without a long-term need and should only be used as a last option after failure to respond to other antacid classes such as aluminum (hydroxide)-, calcium (carbonate)-, and magnesium (hydroxide)-based antacids, as well as histamine H2 receptor antagonists (famotidine, ranitidine, cimetidine etc.).⁶

Pharmacists and pharmacist interns can play a pivotal role in helping patients who are shopping for OTC PPIs by asking open-ended questions such as what other prescription and OTC medications they are currently using; who is going to use it (to gauge about patients’ age and/or gender); what symptoms they are experiencing; how long have they been experiencing those symptoms; and what other medications they have tried so far, if any. Additionally, emerging research studies suggest that patients on long-term PPI treatment also experience 1 or more chronic health conditions, and a growing amount of evidence suggests untoward health effects of long-term PPI treatment in such patients. Furthermore, there is a paucity of research data examining whether there are any age-related, gender-based, and/or economic status-based differences in clinically unjustifiable OTC PPIs use. For instance, one study reported that treatment with a PPI versus placebo for the symptomatic relief of GERD in infants (age < 12 months) was statistically insignificant, and another study proposed increased adverse effects with PPI use in infants.¹⁰ Thus, therapeutic benefits of using PPI for GERD in infants is questionable.

There are still some unaddressed questions about PPI use, and answering those could potentially help navigate many of the pitfalls of therapeutic duplication with unintentional and concomitant use of prescription PPIs and OTC PPIs. For example, there is no online platform analogous to those used by other health care professionals to track controlled or scheduled drug prescriptions, or pseudoephedrine-containing products sold. Availability of such a platform to pharmacists could help examine the amount of OTC PPIs that have been purchased by a patient per week or per month. Additionally, streamlining and feeding such OTC PPI use data and history of prescription PPIs to online medication therapy management platforms could potentially help pharmacists reconcile PPI therapy and rule out the possibility of therapeutic duplication with prescription-based PPIs.

Another approach to minimize potentially unjustifiable chronic use of PPIs could be pharmacy-based computer platforms that offer pharmacy team members an option to opt out of auto-filling PPI prescriptions. Such systems should only authorize autofill with a special permission and proper documentation validating rationale for long-term PPI use. Additionally, there is a trend to delegate prescription writing by physicians to mid-level practitioners, with an increased risk of prescribing excessive quantities (90 days instead of 30 days), and/or a greater number of refills for an unnecessarily long treatment duration. Multiple factors potentially play an important role in excess prescribing of PPIs by mid-level practitioners, including their limited understanding about pharmacological use and adverse effects consequences of long-term PPIs use, their ignorance of current OTC PPI use by the patient, or pressure to keep patients’ business by prescribing what the patient wants.

In a nutshell, OTC PPIs could definitely prove to be a boon for patients if there is a multi-faceted and intentional approach by a team of pharmacists, prescribers, and managers for OTC PPIs necessitating a clinically justifiable use, and minimizing potential therapy duplication of OTC PPI use along with prescription PPIs.

References

1. Pediatric Postmarketing Pharmacovigilance. FDA. April 3, 2018. Accessed September 5, 2024. https://www.fda.gov/media/113569/download#:~:text=Prilosec%20(omeprazole%3B%20NDA%2019810),capsule%20on%20September%2014%2C%201989

2. Targownik LE, Fisher DA, Saini SD. AGA clinical practice update on de-prescribing of proton pump inhibitors: expert review. Gastroenterology. 2022;162(4):1334-1342. doi:10.1053/j.gastro.2021.12.247

3. Bustillos H, Leer K, Kitten A, Reveles KR. A cross-sectional study of national outpatient gastric acid suppressant prescribing in the United States between 2009 and 2015. PLoS One. 201813(11):e0208461. doi:10.1371/journal.pone.0208461

4. Over-the-Counter (OTC) Heartburn Treatment. FDA. Updated November 27, 2023. Accessed September 5, 2024. https://www.fda.gov/drugs/understanding-over-counter-medicines/over-counter-otc-heartburn-treatment

5. Freedberg DE, Kim LS, Yang YX. The risks and benefits of long-term use of proton pump inhibitors: expert review and best practice advice from the American Gastroenterological Association. Gastroenterology. 2017;152(4):706-715. doi:10.1053/j.gastro.2017.01.031

6. FDA Drug Safety Communication: Possible increased risk of fractures of the hip, wrist, and spine with the use of proton pump inhibitors. FDA. Updated August 3, 2017. Accessed September 5, 2024. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/fda-drug-safety-communication-possible-increased-risk-fractures-hip-wrist-and-spine-use-proton-pump

7. Lazarus B, Chen Y, Wilson FP, Sang Y, Chang AR, Coresh J, Grams ME. Proton pump inhibitor use and the risk of chronic kidney disease. JAMA Intern Med. 2016;176(2):238-246. doi:10.1001/jamainternmed.2015.7193

8. Inghammar M, Svantrom H, Voldstedlund M, Melbye M, Hviid A, Molbak K, Pasternak B. Proton-pump inhibitor use and the risk of community-associated Clostridium difficile infection. Clin Infect Dis. 2021;72(12):e1084-e1089. doi:10.1093/cid.ciaa1857

9. Higginbotham TW. Effectiveness and safety of proton pump inhibitors in infantile gastroesophageal reflux disease. Ann Pharmacother. 2010;44(3):572-576. doi:10.1345/aph.1M519

10. Ariel H, Cooke JP. Cardiovascular risk of proton pump inhibitors. Methodist Debakey Cardiovasc J. 2019;15(3):214-219.