Concerns of Long Term Stomach Medications (PPIs)

Gastric acid has long been known to be a major contributing factor in various upper gastrointestinal illnesses. Nearly three decades of targeted efforts led to the launch of the first proton pump inhibitor (PPI), omeprazole, in 1988. Several other PPIs were introduced subsequently-pantoprazole, lansoprazole, esomeprazole, rabeprazole, ilaprazole and dexlansoprazole. The availability of PPI changed the landscape of management of acid-related gastrointestinal disorders.

Proton pump inhibitor (PPIs) was first approved for use in the year 1989.These medicines are used for acid suppression of stomach and are more potent for acid inhibition during daytime. They are effective in treating a variety of gastric acid-related disorders. They are freely available and based on current evidence, use of PPIs for inappropriate indications and duration appears to be common. Over the years, concerns have been raised on the safety of PPIs as they have been associated with several adverse effects. Hence, there is a need to promote the use of PPIs for appropriate indication and duration.

PPIs are the most commonly prescribed medication worldwide. It has been seen that 25-70 % of prescriptions do not have appropriate indications. One of the Indian studies shows that 91% of the prescriptions of PPIs do not have appropriate indication. Large number of affected patients are provided ongoing treatment with PPI administration for several years.

Accepted Indications for PPI Use

• Erosive Esophagitis.
• H Pylori Eradication.
• Dyspepsia
• Gastric Ulcer.
• Pathologic hypersecretory conditions.
• Critically ill patients on prolonged mechanical ventilation.
• Functional Dyspepsia.
• Approved indications for long term PPI use.
• Maintenance of symptom control in GERD.
• Maintenance of healing of erosive esophagitis.
• Barrett’s esophagus.
• NSAID users at increased risk (Age >70, prior ulcer, high dose NSAIDS etc.)
• Antiplatelet agent users with increased risk.
• Pathological hypersecretory conditions.

Disadvantages of long term PPI

1. Allergic reaction.
2. Gastrointestinal infections: PPIs suppress the acid secretion which can lead to growth of bacteria which are otherwise suppressed by acid environment.
3. Pneumonia: The function of immune cells may be impaired due to PPI use and can lead to respiratory infections.
4. Small intestinal bacterial overgrowth: As a result of alterations in the gut microbiome due to PPI use.
5. Iron deficiency.
7. Bone fractures.
8. Drug interactions: The therapeutic efficacy of some drugs may be less if used along with PPIs.
9. Kidney injury: Although not an established complication of PPI use, but, kidney injury in form of interstitial nephritis or chronic kidney disease has been reported.

A study done in 2021 showed that the use of proton pump inhibitors is associated with a 45% increased risk of gastric cancer compared with the use of histamine-2 receptor antagonists. Gastric cancer risk increased with cumulative duration of use, cumulative omeprazole equivalents, and time since treatment initiation.

Optimizing the use of PPI

There are four potential scenarios of inappropriate use of PPIs:

• For inappropriate indication.
• For longer than the recommended duration.
• At a higher than the recommended dose.
• Failure to use PPIs when it is clinically indicated.

Large number of studies published over last two decades have shown inappropriate use in significant number of patients. PPIs should be discontinued if there is no definite indication.

For prescribing PPIs, strategy of both dose tapering and abrupt discontinuation has shown similar results. The strategy, however, needs to be individualized and flexible.

1. For patients with mild erosive esophagitis, uninvestigated gastroesophageal reflux symptoms a standard dose of PPI is recommended for a maximum of 8 weeks.
2. For patients with non-cardiac chest pain or extraesophageal symptoms of GERD, a PPI trial of up to 8 weeks can be instituted.
3. Patients not responding to therapeutic trial of PPIs require objective evaluation for the diagnosis of GERD.
4. In patients with uninvestigated dyspepsia without alarm features, prolonged or continuous use of PPIs is not recommended.
5. Standard dose of PPI prophylaxis may be introduced in patients receiving single antiplatelet(aspirin) drug in the presence of additional risk factors or in those on dual anti platelets.
6. For patients on anticoagulation (warfarin etc.), standard dose of PPI prophylaxis is recommended if thereare additional risk factors.
7. In patients on short term or long-term steroids, routine PPI prophylaxis is not recommended.
8. Routine PPI prophylaxis is not recommended for all patients on NSAIDS (pain killers). Risk assessment for the GI complications needs to be made before prescribing PPIs in these patients.
9. Use of PPIs should be discouraged in children below 1 year of age.
10. PPIs can be used during second or third trimester of pregnancy if needed. The use of PPIs should be avoided unless there is strong indication during the first trimester.
11. There is no need to co-prescribe PPIs routinely in patients in whom antibiotics are prescribed.

PPIs should be only used whenever necessary. Although very safe, PPIs can lead to various adverse events. The people need to be aware about the side effects of the PPIs if used without a prescription.

Additionally, the unnecessary use of PPIs increases the financial burden on the patients. In USA annual expenditure on PPIs is greater than 11 billion dollars and globally the cost is greater than 25 billion dollars per year. The best strategy to follow should be prescribing PPIs in the lowest possible dose for short term basis with appropriate indications when benefits outweigh any adverse effects.

(The Author is MD/DNB, Consultant Gastroenterologist and Hepatologist, Life Member Indian Society of Gastroenterology. Feedback: [email protected])