How can you prevent painkiller-related peptic ulcers?
When taken for a long time, painkillers like diclofenac and ibuprofen can lead to ulcers in the stomach and duodenum. 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 inflammation 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. The duodenum is the first part of the intestine just behind the stomach.
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 stomach lining becomes more susceptible to damage from stomach acid. It can then 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, although less often. One of the things misoprostol does is increase the production of gastric (stomach) mucus, which helps protect the stomach wall. In Germany, misoprostol is available as a combination drug together with the painkiller diclofenac.
Risk factors for peptic ulcers
Not everyone who regularly 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 painkillers 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 re-uptake inhibitor (SSRI) antidepressant as well as a painkiller.
Younger people who don't have any risk factors aren't likely to get peptic ulcers. So they hardly benefit from taking medication to prevent 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 more than 21,000 participants.
The people in the studies were mainly men and women who had osteoarthritis or a rheumatic disease. 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 proton pump inhibitors, 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 proton pump inhibitors 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 lasted up to six months. They showed that, compared to a placebo, all of these proton pump inhibitors clearly lowered the risk of getting peptic ulcers:
- Without a proton pump inhibitor, 36 out of 100 people developed an ulcer.
- With a proton pump inhibitor, 14 out of 100 people developed a peptic ulcer.
In other words: Proton pump inhibitors prevented the development of NSAID-related peptic ulcers in 22 out of 100 people.
Proton pump inhibitors may cause headaches, diarrhea, constipation and stomach pain. Only a few people in the studies stopped their treatment early due to side effects.
But it's not clear whether the long-term use of proton pump inhibitors is safe. It has been observed that hip fractures, spinal fractures and wrist fractures are more common in people over the age of 50 who have 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 an H2 blocker, 36 out of 100 people developed an ulcer.
- With an H2 blocker, 15 out of 100 people developed an ulcer.
In other words, higher doses of H2 blockers prevented peptic ulcers in 21 out of 100 people.
The effective doses in the trials were 40 mg twice daily for famotidine and 300 mg twice daily for ranitidine. These medications were also well tolerated at higher doses. Side effects such as headaches, diarrhea or constipation may occur, though.
Misoprostol is effective, but has more 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 proton pump inhibitors, more people in the studies on misoprostol stopped their treatment. There is very little research on the combination drug (containing diclofenac and misoprostol) that is available in Germany. So it's not clear whether it 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. Proton pump inhibitors 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 doesn't seem to be a problem when taking proton pump inhibitors.
The risk of stomach and bowel (gastrointestinal) problems can be reduced by taking the lowest possible dose of painkillers, and only taking them for as long as necessary. Acetaminophen (paracetamol) may sometimes be an alternative to NSAIDs. It doesn't increase the risk of peptic ulcers and is often just as effective. But it has side effects too: For instance, it may cause liver damage if the dose is too high or if you take it regularly.
It's best to talk to a doctor about how high your own personal risk of getting a peptic ulcer is, as well as what medications you could take to protect your stomach.
Robert Koch-Institut (RKI), Statistisches Bundesamt (Destatis). Gastritis, Magen- und Zwölffingerdarmgeschwüre. Berlin: RKI; 2013. (Gesundheitsberichterstattung des Bundes; Heft 55).
Rostom A, Dube C, Wells GA, Tugwell P, Welch V, Jolicoeur E et al. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst Rev 2002; (4): CD002296.
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