Gastritis: How can you prevent peptic ulcers caused by painkillers?

When taken for a long time, painkillers like diclofenac and ibuprofen can lead to ulcers in the stomach and bowel. But the risk of this happening can be clearly reduced by also taking medication to protect your stomach.

Many people who have osteoarthritis or rheumatoid arthritis regularly take non-steroidal anti-inflammatory drugs (NSAIDs) in order to reduce pain or swelling in the joints. Commonly used NSAIDs include acetylsalicylic acid (the drug in medicines like Aspirin), ibuprofen, diclofenac and naproxen.

One disadvantage of these medications is that they often cause stomach and bowel problems when taken for several weeks or months. Stomach ulcers (gastric ulcers) or duodenal ulcers may develop as a result. These ulcers are collectively known as peptic ulcers.

NSAIDs reduce the production of the hormone prostaglandin. One of the things prostaglandin does is increase the production of gastric (stomach) mucus and substances that neutralize stomach acid. If there is too little prostaglandin, the protective function is disturbed and the stomach lining becomes more susceptible to damage from stomach acid. It can become inflamed, and eventually ulcers may develop.

Medication to prevent ulcers

Various medications can lower the risk of getting a peptic ulcer. These include, in particular, drugs called proton pump inhibitors (PPIs) and H2 blockers. Both of these types of drugs reduce the production of stomach acid. In Germany, the most commonly used PPIs are omeprazole and pantoprazole. The H2 blocker that is normally used is ranitidine.

The hormone-like drug misoprostol is sometimes used too. One of the things misoprostol does is increase the production of gastric (stomach) mucus, which helps protect the stomach wall. In Germany, misoprostol is marketed together with the NSAID diclofenac in the form of a combination drug.

Risk factors for peptic ulcers

Not everyone who takes NSAIDs will also need to take medication to protect their stomach. This will mainly depend on your personal risk of developing a peptic ulcer.
Peptic ulcers are more likely to develop in people who

are over the age of 65,
have had a peptic ulcer in the past,
take several different NSAIDs at once – for instance, including acetylsalicylic acid for the prevention of complications following a heart attack or stroke,
take steroids too,
take a selective serotonin reuptake inhibitor (SSRI) antidepressant as well as an NSAID.
Younger people who do not have any risk factors are not likely to get peptic ulcers. So they hardly benefit from taking medication to prevent the development of peptic ulcers.

Research on the prevention of peptic ulcers

A group of researchers from the Cochrane Collaboration – an international network of researchers – wanted to find out which medications can prevent the development of peptic ulcers. To do so, they looked for studies where NSAIDs were combined with PPIs, H2 blockers or misoprostol. The researchers found 41 suitable studies with a total of 21,000 participants.

The people in the studies were mainly men and women who had osteoarthritis or a rheumatic disease such as rheumatoid arthritis.
All of them took one or several NSAIDs for at least three weeks and had a fairly high risk of getting a peptic ulcer. A number of the studies compared PPIs, H2 blockers or misoprostol with a placebo (dummy drug) or with each other. The participants were observed for up to one year.
Regardless of whether they had symptoms, in almost all of the studies the participants had a gastroscopy to see whether they had an ulcer in their stomach or duodenum.

Proton pump inhibitors lower the risk of peptic ulcers

The PPIs used in the studies were lansoprazole (15 mg or 30 mg per day), omeprazole (20 mg per day) and pantoprazole (40 mg per day). The studies on these drugs lasted up to six months. They showed that, compared to a placebo, all of these PPIs clearly lowered the risk of getting peptic ulcers:

Without treatment: 36 out of 100 people who took a placebo developed a peptic ulcer.
With treatment: Only 14 out of 100 people who took a PPI developed a peptic ulcer.
In other words: Proton pump inhibitors prevented the development of NSAID-induced peptic ulcers in 22 out of 100 people.

The studies also looked at whether people stopped taking the PPI because of side effects. This was not the case. This suggests that PPIs are quite well tolerated. But it is not clear whether the long-term use of PPIs is safe.

In May 2010 the U.S. regulatory authority FDA decided that U.S. package inserts should include the information that the long-term use of PPIs could increase the risk of bone fractures.
It had been observed that hip fractures, spinal fractures and wrist fractures were more common in people over the age of 50 who had taken PPIs in a high dose or for longer than a year. It is also thought that the long-term use of PPIs might increase the risk of intestinal infections and pulmonary (lung) infections or nephritis (inflammation of the kidney).

H2 blockers: Effectiveness depends on dose

The studies on H2 blockers mainly looked at the drugs famotidine and ranitidine. These studies lasted up to one year. Both drugs were shown to prevent peptic ulcers, but their effectiveness greatly depended on the dose taken.
When taken at lower doses, the medications only reduced the risk of duodenal ulcers. When taken at higher doses, they effectively prevented both stomach ulcers and duodenal ulcers:

Without treatment: 36 out of 100 people who took a placebo developed a peptic ulcer.
With treatment: Only 15 out of 100 people who took an H2 blocker developed a peptic ulcer.
In other words, higher doses of H2 blockers prevented peptic ulcers in 21 out of 100 people. The doses that were found to be effective in the studies were 40 mg of famotidine twice a day and 300 mg of ranitidine twice a day. These drugs were also well tolerated when taken at higher doses.

Misoprostol is effective, but often has side effects

There were also a lot of studies on misoprostol. The studies showed that this drug can prevent the development of peptic ulcers too. But misoprostol has a disadvantage: it often causes side effects, particularly diarrhea and stomach cramps. Because of this, compared to the people in the studies on PPIs, more people in the studies on misoprostol stopped their treatment. There is very little research on the combination drug that is available in Germany, containing diclofenac and misoprostol. So it is not clear whether this combination drug has any advantages or disadvantages compared to other treatments.

Making a decision and considering alternative options

All three types of “stomach-protecting” medication can lower the risk of getting peptic ulcers. PPIs and H2 blockers appear to be very well tolerated. But it is important to make sure the dose of H2 blockers is high enough. H2 blockers can become less effective over time because your body gets used to them. This does not seem to be a problem when taking PPIs.

The risk of stomach bleeding can be reduced from the start by taking the lowest possible dose of NSAIDs and only taking them for as long as necessary. Acetaminophen (paracetamol) may sometimes be an alternative to NSAIDs. It does not increase the risk of peptic ulcers and can often provide enough pain relief. But this drug can also have side effects, so it is important to take the right dose. For instance, it can cause liver damage if the dose is too high or you take it too often.

G Mohan.