Long-term omeprazole use: risks, monitoring and safe withdrawal

Proton pump inhibitors such as omeprazole are among the most widely prescribed medications in the UK, with an estimated 50 million PPI prescriptions dispensed annually by the NHS.

While they are highly effective for short-term acid suppression, growing evidence suggests that prolonged use beyond the original clinical indication carries measurable risks.

In my practice, I regularly encounter patients who were started on omeprazole years ago for a self-limiting condition and have continued taking it without review.

NICE estimates that up to 50% of patients on long-term PPIs may not have a current indication that justifies continued use.

The concerns are not about acute toxicity. Omeprazole is a safe drug in the short term.

Rather, they relate to the physiological consequences of sustained acid suppression: impaired nutrient absorption, altered gut microbiome, effects on bone metabolism and potential renal impact.

This does not mean that long-term PPIs are never appropriate.

Patients with Barrett's oesophagus, severe oesophagitis (Los Angeles grade C or D), or a history of bleeding peptic ulcers have clear indications for ongoing treatment.

The issue is the large number of patients taking PPIs without a compelling reason to continue.

The MHRA issued a Drug Safety Update in 2012 confirming that long-term PPI use (especially at high doses and for durations exceeding one year) is associated with a modest increase in the risk of hip, wrist and vertebral fractures.

The proposed mechanism relates to reduced calcium absorption. Gastric acid is needed to solubilise calcium salts and facilitate their absorption in the duodenum.

By suppressing acid production, PPIs may impair calcium uptake, leading to gradual bone demineralisation.

Key findings from the evidence:

• A meta-analysis of 18 observational studies found a 26% increased risk of hip fracture with PPI use
• The risk appears to be dose-dependent and duration-dependent
• Patients over 65, those with existing osteoporosis, and those on corticosteroids are at highest risk

What I recommend to my patients:

• Ensure adequate calcium intake (at least 700 mg daily from diet or supplements)
• Maintain vitamin D levels (consider supplementation, particularly in winter)
• Weight-bearing exercise to support bone density
• If on long-term PPIs and at fracture risk, discuss a DEXA scan with your GP

For patients who do not have a strong ongoing indication, reducing or stopping omeprazole is the most effective way to mitigate this risk.

Sustained acid suppression with omeprazole affects the absorption of several essential nutrients. In my clinic, I monitor these regularly in patients on long-term PPIs.

Vitamin B12 deficiency:

Gastric acid and pepsin are required to cleave vitamin B12 from dietary proteins.

Long-term PPI use reduces this process, and observational studies have shown a 65% increased risk of B12 deficiency in patients taking PPIs for more than 2 years.

Symptoms include fatigue, paraesthesia, cognitive impairment and macrocytic anaemia.

Iron deficiency:

Non-haem iron (the primary form in plant-based foods) requires an acidic environment for reduction to its absorbable ferrous form.

While clinical iron deficiency from PPI use alone is uncommon, it can be a contributing factor in patients with borderline dietary intake, particularly vegetarians and the elderly.

Hypomagnesaemia:

This is the nutrient deficiency of greatest clinical concern.

The MHRA has issued specific warnings about PPI-associated hypomagnesaemia, which can present with muscle cramps, tremor, cardiac arrhythmias and seizures.

The mechanism is not fully understood but appears to involve impaired intestinal magnesium absorption.

The MHRA recommends:

• Checking magnesium levels before starting long-term PPIs
• Periodic monitoring during prolonged treatment
• Particular vigilance in patients also taking diuretics or digoxin

I check a full blood count, B12, folate, ferritin and magnesium at least annually in all patients on continuous PPI therapy.

Gastric acid serves as an important defence against ingested pathogens. By raising gastric pH, omeprazole may increase susceptibility to certain gastrointestinal infections.

C. difficile infection:

Multiple studies have demonstrated a 1.5 to 2.7-fold increased risk of Clostridioides difficile infection in PPI users.

This is particularly relevant for elderly patients, those in care homes, and patients recently treated with antibiotics.

NHS England has included PPI review as part of its antimicrobial stewardship guidance.

Other enteric infections:

There is evidence of increased risk of Campylobacter and Salmonella infections in PPI users.

The absolute risk increase is small, but it is worth considering in patients planning travel to areas with poor sanitation.

Small intestinal bacterial overgrowth (SIBO):

By reducing the bactericidal effect of gastric acid, long-term PPI use may promote bacterial overgrowth in the small bowel.

Symptoms can include bloating, diarrhoea, flatulence and abdominal discomfort, which may be mistaken for ongoing dyspepsia.

I advise patients on long-term omeprazole to seek medical attention promptly if they develop persistent diarrhoea, particularly after a course of antibiotics, and to mention their PPI use to the treating clinician.

Deprescribing PPIs is an area I feel strongly about. Many patients can successfully reduce or stop omeprazole with appropriate support.

NICE and NHS England both advocate for regular PPI review and dose optimisation.

Step-down approach:

1. Reduce the dose first: switch from 40 mg to 20 mg, or from 20 mg to 10 mg. Maintain the reduced dose for 2 to 4 weeks
2. Switch to alternate-day dosing: take omeprazole every other day for 2 to 4 weeks
3. Trial complete withdrawal: stop omeprazole and use antacids (such as Gaviscon) as needed for breakthrough symptoms

Rebound acid hypersecretion:

Patients should be warned that stopping omeprazole, especially after long-term use, can cause a temporary rebound increase in acid production.

This is a physiological response and does not mean the original condition has returned. Symptoms typically settle within 2 to 4 weeks.

When not to stop:

Long-term PPI therapy remains appropriate for:

• Barrett's oesophagus
• Severe erosive oesophagitis (Los Angeles grade C/D)
• Previous peptic ulcer with bleeding or perforation
• Ongoing NSAID use in high-risk patients
• Zollinger-Ellison syndrome

For patients with a clear indication for ongoing treatment, the goal should be the lowest effective dose with regular monitoring for side effects.