What are alternative treatments for peptic ulcers in patients who cannot use Proton Pump Inhibitors (PPIs)?

From the Guidelines

For patients who cannot use Proton Pump Inhibitors (PPIs), several effective alternative treatments for peptic ulcers are available, including H2 receptor antagonists, antacids, sucralfate, bismuth subsalicylate, and misoprostol, as well as antibiotic regimens for H. pylori-associated ulcers.

Alternative Treatments

• H2 receptor antagonists such as famotidine (20-40mg twice daily), ranitidine (150mg twice daily), or cimetidine (400mg twice daily) can reduce stomach acid production, though they are less potent than PPIs 1.
• Antacids containing aluminum hydroxide, magnesium hydroxide, or calcium carbonate can provide quick symptom relief when taken as needed, but require frequent dosing.
• Sucralfate (1g four times daily) forms a protective coating over ulcers to promote healing.
• Bismuth subsalicylate, often combined with antibiotics in quadruple therapy, helps eradicate H. pylori infection.
• Misoprostol (200mcg four times daily) can protect the stomach lining but may cause diarrhea.

Antibiotic Regimens

For H. pylori-associated ulcers, antibiotic regimens remain essential even without PPIs, typically including amoxicillin, clarithromycin, metronidazole, or tetracycline for 10-14 days, as recommended by the WSES guidelines 1.

Lifestyle Modifications

Lifestyle modifications are also important, including avoiding NSAIDs, alcohol, smoking, and spicy foods, as these can exacerbate ulcers and reduce the effectiveness of treatment 1.

Potassium-Competitive Acid Blockers (P-CABs)

P-CABs, such as vonoprazan, may be a useful alternative to PPIs in certain cases, particularly for patients with severe erosive esophagitis or those who have failed PPI therapy, although their high cost and limited availability may limit their use as first-line therapy 1. The choice of alternative treatment should be based on the individual patient's needs and medical history, and should prioritize the reduction of morbidity, mortality, and improvement of quality of life.

From the FDA Drug Label

It is therefore not possible to tell whether the ability of misoprostol to reduce the risk of gastric ulcer is the result of its antisecretory effect, its mucosal protective effect, or both. Misoprostol produces a moderate decrease in pepsin concentration during basal conditions, but not during histamine stimulation Misoprostol, over the range of 50–200 mcg, inhibits basal and nocturnal gastric acid secretion, and acid secretion in response to a variety of stimuli, including meals, histamine, pentagastrin, and coffee Reducing the Risk of Gastric Ulcers Caused by Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)Two 12-week, randomized, double-blind trials in osteoarthritic patients who had gastrointestinal symptoms but no ulcer on endoscopy while taking an NSAID compared the ability of 200 mcg of misoprostol, 100 mcg of misoprostol, and placebo to reduce the risk of gastric ulcer (GU) formation

Alternative treatments for peptic ulcers in patients who cannot use Proton Pump Inhibitors (PPIs) include:

• Misoprostol: a prostaglandin E1 analogue that reduces gastric acid secretion and has mucosal protective effects, as shown in studies 2
• H2-antagonists: such as ranitidine, which inhibits gastric acid secretion and has been shown to be effective in healing duodenal and gastric ulcers, as well as preventing recurrence of ulcers, as shown in studies 3 and 3
• Antacids: which can provide symptomatic relief of pain and heartburn, as mentioned in the drug label for ranitidine 3

From the Research

Alternative Treatments for Peptic Ulcers

In patients who cannot use Proton Pump Inhibitors (PPIs), alternative treatments for peptic ulcers include:

• Histamine 2-receptor antagonists (H2RAs) 4, 5, 6
• Misoprostol 5, 7
• Sucralfate 5

Efficacy of Alternative Treatments

The efficacy of these alternative treatments varies:

• H2RAs may be less effective than PPIs in preventing persistent or recurrent bleeding from peptic ulcers 4
• Misoprostol may increase the risk of incident ulcers compared to PPIs 5
• Sucralfate has not been directly compared to PPIs in the prevention of peptic ulcers 5

Safety of Alternative Treatments

The safety of these alternative treatments also varies:

• H2RAs may have a similar safety profile to PPIs 6
• Misoprostol may have a higher risk of adverse events compared to PPIs 5
• Sucralfate has not been directly compared to PPIs in terms of safety 5

Comparison of Alternative Treatments

Comparing the safety and efficacy of alternative treatments is crucial:

• A systematic review found that omeprazole (a PPI) is superior to H2RAs in healing ulcers and bringing pain relief 6
• Another study found that PPIs are more effective than H2RAs in preventing persistent or recurrent bleeding from peptic ulcers 4
• A network meta-analysis found that different PPIs have similar effectiveness and safety profiles 7