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Proton Pump Inhibitors (PPI): Are they being used judiciously?
The proton pump inhibitor (PPI), introduced in 1989, reflected a major medical therapeutic breakthrough in the treatment of peptic ulcers and GORD, resulting in more rapid healing of the lesions and symptom relief. Now, PPIs are the cornerstone in the management of gastric and duodenal ulcers, dyspepsia, gastro-oesophageal reflux disease (GORD), Zollinger–Ellison (ZE) syndrome, Helicobacter pylori (H. pylori) eradication, and prevention and treatment of non-steroidal anti-inflammatory (NSAID)-associated ulcers.
In 2020, omeprazole was ranked as the second-highest dispensed item in England, with almost 35 million prescriptions filled and an annual cost of £82 million. Apart from some specific acid-related diseases (e.g., ZE syndrome and Barrett’s oesophagus), it is recommended that PPIs should be discontinued 4 to 8 weeks after initiation. In practice, this hardly is the case!
Although PPIs are generally considered safe for short-term use, evidence of serious side effects with long-term use is mounting. These potential risks include increased risk of pneumonia, enteric infection, bone fracture, gastrointestinal tract cancers, and reduced absorption of vitamins and minerals. Below we shall discuss if indefinite treatment with PPIs is all that harmless.
PPI wins:
Gastro-oesophageal reflux disease
The treatment of suspected or confirmed GORD. The treatment regimen depends on the severity of symptoms.
Non-steroidal anti-inflammatory drug (NSAID)-associated ulcers
The prevention and treatment of NSAID-induced erosions and ulcers in at risk patients and are often prescribed to treat NSAID-induced dyspepsia. PPIs should be taken daily, rather than “as needed”, to prevent NSAID-related adverse effects because ulceration or bleeding of the gastrointestinal tract can occur in the absence of dyspepsia.
Eradication treatment for H. pylori
Recommended for the eradication of H. pylori as part of a triple treatment regimen.
Other indications
A proton pump inhibitor can be used to reduce the degradation of pancreatic enzyme supplements in patients with cystic fibrosis. They can also be used to control excessive secretion of gastric acid in Zollinger–Ellison syndrome; high doses are often required. Another indication for proton pump inhibitors is stress ulcer prophylaxis.
Are they completely safe?
The rate of adverse effects associated with PPI treatment is relatively low. However, given that each practice is likely to have 100s of patients taking PPIs, clinicians need to be aware of the potential risks. Let’s explore these risks a bit further:
Increased risk of infection.
Gastric acid suppression with PPIs increases the risk of infection with gastrointestinal or respiratory pathogens. The higher risk is thought to be due to a reduction in the effectiveness of the “acid wall” stomach barrier. This allows viable pathogens to travel up or down the gastrointestinal tract and also colonise the lower airways.
Malabsorption of nutrients.
Acid in the gut increases the solubility of elements, e.g. calcium and iron, from insoluble salts and makes protein-bound vitamins, e.g. vitamin B12. However, this association is controversial. In most cases, patients can be reassured that a balanced diet, including essential elements and minerals (e.g. calcium, iron, folate, magnesium) is adequate to address this risk.
A small increase in fracture risk.
An increased risk of osteoporosis should be considered in post-menopausal females who are taking PPIs long-term, especially if they have other risk factors, e.g. a family history of osteoporosis or long-term corticosteroid use.
A study11 of more than 15 000 instances of osteoporosis-related fractures found that after five years of PPI use patients had an increased risk of hip fracture, and the risk increased further when treatment was continued for seven years. Furthermore, patients taking PPIs for more than seven years also had an increased risk of non-hip fractures.
Hypomagnesemia.
Hypomagnesaemia, and possibly hypocalcaemia is known, although rare, adverse effects of PPI use. Symptoms of hypomagnesaemia are non-specific and may include muscle cramps, weakness, irritability, or confusion.
Routine testing of magnesium levels in patients taking PPIs is generally not recommended. However, if a patient has been taking a PPI long-term and they present with unexplained symptoms that are consistent with hypomagnesaemia, consider requesting a serum magnesium level.
Vitamin B12 deficiency in older patients on long-term PPIs.
PPIs decreased the absorption of vitamin B12 from food. In older patients with poor nutrition, who are taking PPIs long-term, consider testing vitamin B12 levels periodically.
So, can we just STOP them?
One word answer for those who have been taking PPIs for long time, is NO. Below we shall discuss, why.
Rebound acid secretion can occur when PPIs are withdrawn; one study2 found that more than 40% of asymptomatic patients experienced dyspepsia one week after completing a four-week treatment course of pantoprazole. Serum markers suggest that acid secretion one week following cessation of PPI treatment can be significantly increased above pre-treatment levels. This should return to normal within two weeks.
Medicines that contain both an antacid and an anti-foaming agent, e.g. Gaviscon liquid, Acidex oral liquid, Gaviscon Double Strength tablets are likely to be the most effective treatment for rebound acid secretion.
- Review all existing patients taking PPIs long-term and assess whether the indication for treatment remains and whether the dose of PPI can be reduced.
- When new patients are started on PPIs, discuss the expected duration of treatment, and have a plan for stepping down or stopping treatment.
- In most situations, patients do not need to be started on PPI treatment in primary care with 40 mg omeprazole, daily (or equivalent).
- Consider whether “as needed” use would be more appropriate for patients than taking PPIs daily.
- Ensure patients are prepared for rebound acid secretion which may occur when PPI treatment is withdrawn; the products such as Gaviscon, Acidex can be recommended.
How we can play part in reducing unnecessarily prolonged and/or high dose use of PPIs
- Review all existing patients taking PPIs long-term and assess whether the indication for treatment remains and whether the dose of PPI can be reduced.
- When new patients are started on PPIs, discuss the expected duration of treatment, and have a plan for stepping down or stopping treatment.
- In most situations, patients do not need to be started on PPI treatment in primary care with 40 mg omeprazole, daily (or equivalent).
- Consider whether “as needed” use would be more appropriate for patients than taking PPIs daily.
- Ensure patients are prepared for rebound acid secretion which may occur when PPI treatment is withdrawn; the products such as Gaviscon, Acidex can be recommended.
References:
· https://www.health.harvard.edu/newsletter_article/proton-pump-inhibitors
· https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885718/
· https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548122/#:~:text=The%20proton%20pump%20inhibitor%20(PPI,which%20is%20activated%20by%20acid.
· https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10427555/
· https://bnf.nice.org.uk/drugs/sodium-alginate-with-potassium-bicarbonate/medicinal-forms/#oral-suspension