Proton pump inhibitors (PPI) – patient guide

Patient guide: Proton pump inhibitors (PPI)

Proton pump inhibitors – also called PPIs or acid pump inhibitors – are a group of medicines that suppress the production of stomach acid. You may have been prescribed them for heartburn, peptic ulcers, acid reflux, or as protection if you take anti-inflammatory painkillers (NSAIDs). This guide explains what PPIs are, the difference between the most commonly used types, typical treatment courses, side effects, and how stopping is decided together with your doctor.

For the clinical background article on long-term use and the underlying research figures, see our blog article on proton pump inhibitors.

What is a proton pump inhibitor?

The lining of the stomach contains small "acid pumps" that release hydrochloric acid into the stomach. The acid helps break down food and kills bacteria. When the pumps work too strongly – or when the lining of the oesophagus or stomach is irritated – the acid can cause heartburn, pain or ulcers. PPIs bind to the pumps and switch them off, so acid production drops sharply.

The four most commonly used PPIs in Denmark are:

• Omeprazole (Losec and generics).
• Pantoprazole (Pantoloc and generics).
• Esomeprazole (Nexium) – chemically a close relative of omeprazole.
• Lansoprazole (Lanzo).

Omeprazole

Omeprazole is still widely used. The dose, strength and duration are set by the prescribing doctor based on indication, age, kidney and liver function, pregnancy and other medicines. Whether a product requires a prescription can change over time, so check the current status at the pharmacy or in the official medicines information if you are unsure.

Omeprazole and esomeprazole can weaken the effect of the blood thinner clopidogrel. Because of this, people who take clopidogrel are usually given a different proton pump inhibitor instead. Your doctor decides which treatment is right for you.

Pantoprazole

Pantoprazole works fundamentally like omeprazole. The doctor sets the dose and duration in the individual case. Which PPI is chosen depends on the indication and on your full medication list, and it is a medical judgement.

Typical treatment courses

How long a PPI course lasts depends on what is being treated. The prescribing doctor always sets the concrete plan, but the following are the general frameworks recommended by the Danish College of General Practitioners (DSAM):

• Heartburn/reflux with severe or frequent symptoms: a standard once-daily dose of PPI, with the effect assessed after about 4 weeks. If the effect is only partial, the doctor can increase the dose. For mild reflux disease - without a gastroscopy, or with only mild oesophagitis - it is then often possible to switch to on-demand treatment (taking the medicine only when symptoms occur) or to the lowest dose that keeps symptoms away.
• Confirmed severe oesophagitis (LA grade C-D): here DSAM recommends maintenance treatment with a PPI, because relapse is common. This is not a treatment you should stop on your own.
• Barrett's oesophagus: continuous PPI treatment is recommended here. The dose is adjusted individually according to symptoms and other findings. The treatment reduces acid exposure of the oesophagus, but it does not remove the risk of cancer, and any surveillance programme is agreed separately with your doctor.
• Confirmed stomach ulcer or duodenal ulcer: as a rule, 4 to 6 weeks of PPI treatment, unless there are ongoing risk factors that argue for continuing.
• Treatment of Helicobacter pylori: here the PPI is only part of the eradication course itself, which typically lasts 7 to 14 days, unless your doctor agrees on something different with you.
• Stomach protection for people who continue to need ulcer-causing medicine (for example NSAIDs or blood thinners) and who have a significant risk, such as a previous ulcer complication or several risk factors together: here a PPI is given continuously as prevention for as long as the risk is present.

After 4 to 8 weeks of treatment, the stomach can produce more acid than normal if the PPI is stopped suddenly (rebound acid production). This can make it hard to stop, because symptoms return. Such symptoms after stopping do not automatically mean treatment has to be restarted, and antacids or an alginate can be tried first.

Never start, stop or change prescribed medicine without agreeing it with your treating doctor.

A PPI works best when the tablet is taken some time before a meal, because the acid pumps are activated by food. Follow the timing given on your pack or by your doctor.

Sources: DSAM, clinical guideline "Dyspepsia and gastro-oesophageal reflux disease in adults" (2021): Gastro-oesophageal reflux and Long-term treatment with acid-suppressing medicine. On Barrett's oesophagus: Lægehåndbogen (the Danish physicians' handbook), Barrett's oesophagus, sundhed.dk, updated 29 May 2024.

Side effects with short-term use

Most people tolerate PPIs well. Short courses most often cause:

• Headache.
• Diarrhoea, constipation or bloating.
• Nausea or stomach pain.
• Itching or rash – less common.

For many people these effects settle, but that varies. If they persist, your doctor can switch you to another PPI or adjust the dose. Side effects and their frequencies for your specific product are listed in its package leaflet.

Side effects with long-term use

With long-term use, a distinction is made between recognised side effects that are listed in the official product information, and uncertain statistical associations that come from observational studies and have not been proven to be caused by PPIs.

Recognised side effects from the product information:

• Low magnesium (hypomagnesaemia). Can cause muscle cramps, palpitations and fatigue. Seen mainly with longer-term daily use.
• Allergic kidney inflammation (acute interstitial nephritis). Can develop insidiously. Kidney values are checked when clinically indicated by symptoms, age and other medicines, not as fixed annual screening of every user.
• Vitamin B12 deficiency with long-term use. Stomach acid releases B12 from protein in food, and reduced acid production over a long period is described as a possible cause of B12 deficiency. Tiredness, tingling in the hands or feet, and memory problems can be signs. Blood tests are done when clinically indicated by symptoms or risk factors, not as blanket screening of every PPI user.

Uncertain statistical associations from observational studies (these show association, not proven cause, and PPI users are often older and sicker than the comparison group):

• Bone fractures. Observational studies and meta-analyses have reported a modest statistical association between PPI use and hip and spine fractures, particularly with longer-term or high-dose treatment and in older patients. The results are heterogeneous and do not in themselves show that PPIs are the cause. One possible mechanism is reduced calcium absorption.
• Clostridioides difficile infection. Low stomach acid lets more bacteria pass alive through the stomach. Observational studies have reported an association with PPI use. The size varies between studies and causation is not established.
• Pneumonia. Observational studies have reported an association with PPI use. The findings are inconsistent and it is not settled whether PPIs are the cause.

These possible effects do not mean that a well-indicated treatment should be stopped. Never stop a necessary PPI treatment on your own; discuss with your doctor how long treatment should continue. The point is that the need for a PPI should be reviewed periodically and individually: is there still a reason to continue?

Tapering – how stopping is decided

If your doctor judges that the indication is no longer there, treatment can be stopped. There is no single fixed plan for everyone: gradual dose reduction, switching to on-demand use, or stopping outright can all be considered, depending on dose, duration, indication and symptoms. As mentioned above, the stomach may respond with rebound acid production for a few weeks after stopping, and antacids or an alginate (for example Gaviscon or Samarin) can be used during that period.

Some conditions - such as severe oesophagitis, Barrett's oesophagus, or a continuing high risk of gastrointestinal bleeding - argue for continuing treatment on an ongoing basis, based on your doctor's assessment.

Lifestyle measures can help some people: weight loss if overweight, less coffee and alcohol, no large meals late in the evening, raising the head of the bed, and stopping smoking. They do not replace treatment that is indicated.

Never start, stop or change prescribed medicine without agreeing it with your treating doctor.

When should you contact your doctor?

Contact your GP or the clinic if you:

• Have been on a daily PPI for a prolonged period without a planned review.
• Have recurring heartburn despite regular PPI treatment.
• Develop difficulty swallowing, pain on swallowing, or unexplained weight loss.
• Pass black, tarry stools or vomit blood – call 112 if you feel seriously unwell, otherwise the acute helpline (1813 in the Capital Region, elsewhere your local out-of-hours service) or go to A&E straight away.
• Experience new symptoms such as muscle cramps, tingling in hands or feet, or marked fatigue during long-term therapy.

For long-standing reflux or alarm symptoms a gastroscopy may be needed to assess the lining of the oesophagus and stomach. The clinic holds a provider number under the Danish public health insurance and receives referred patients for services covered by the current agreement; whether a specific service is covered is clarified before the course of treatment.

In short

• Omeprazole and pantoprazole are both used. With clopidogrel, the doctor usually chooses a proton pump inhibitor other than omeprazole or esomeprazole.
• For reflux/heartburn, the effect is assessed after about 4 weeks, after which treatment can often be adjusted or made on-demand.
• Confirmed stomach ulcers are usually treated for 4 to 6 weeks.
• With severe oesophagitis, Barrett's oesophagus, or a high risk of bleeding, continuous treatment is often needed, based on your doctor's assessment.
• The tablet works best some time before a meal. Follow the instructions on your pack.
• Blood tests such as B12 and kidney values are done when clinically indicated, not as routine screening.
• Never start, stop or change prescribed medicine without agreeing it with your treating doctor.