Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

active bleeding ulcer

1st line – endoscopy ± blood transfusion

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ACUTE
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active bleeding ulcer
1st line – 

endoscopy ± blood transfusion

Active gastrointestinal bleeding requires urgent evaluation.[62]​ Most bleeding can be treated endoscopically.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, should be discontinued before treatment. If, however, a patient is taking aspirin for secondary cardiovascular prevention, aspirin should be continued in the acute phase.[62][71] If there is major hemorrhage, specialist hematologic advice should be sought. If cardioprotective aspirin therapy is interrupted, this should be restarted as soon as possible (ideally within 24 hours) of successful endoscopic hemostasis.[71] One observational study in patients with acute myocardial infarction who developed peptic ulcer disease bleeding demonstrated ​​reduced mortality in those who continued aspirin.[72] In another study, in patients at increased risk of cardiovascular disease, restarting low-dose aspirin (postendoscopic control of ulcer bleeding) reduced overall mortality, but was associated with increased recurrent bleeding.[73]

Endoscopy aids in confirming the diagnosis and identifying the cause of bleeding, as well as stopping the bleeding. Epinephrine (adrenaline) is injected into the bleeding site, together with cautery and/or clip application.

Blood transfusion can be considered to resuscitate acute volume loss; a more restrictive transfusion strategy (transfusion only for hemoglobin <7 g/dL) has been shown to significantly improve patient outcomes.[74]

After intervention, the presence of Helicobacter pylori should be assessed, and the patient treated according to guidelines for patients with no active bleeding.

Patients with recurrent bleeding after endoscopic therapy for a bleeding ulcer should undergo repeat endoscopy and endoscopic therapy rather than undergo surgery or transcatheter arterial embolization. Repeat endoscopy and endoscopic therapy successfully prevents further bleeding in approximately three-quarters of these patients, with fewer complications than surgical therapy.[64]

Plus – proton-pump inhibitor (PPI)

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ACUTE
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active bleeding ulcer
Plus – 

proton-pump inhibitor (PPI)

Treatment recommended for ALL patients in selected patient group

The role of pre-endoscopic PPI therapy in patients who present with ulcer bleeding remains an area of ongoing debate.[69]​ ​International consensus recommendations recommend that pre-endoscopic PPI therapy can be considered on the basis that it may downstage the lesion or reduce the need for endoscopic hemostatic treatment, although it should not delay endoscopy.[69][70]​​

After endoscopic hemostasis, high-dose PPI therapy, given either continuously or intermittently for 3 days, is recommended.[62][64][65]​​​ After 72 hours, twice-daily oral treatment with a PPI, for the first 2 weeks, is recommended.[62][64]​​​ These recommendations are based on high-quality evidence documenting a large relative risk reduction in further bleeding and mortality with postendoscopy PPI compared with placebo/no treatment.[64][66][67][68]

Ongoing oral PPI therapy beyond these timeframes depends on the nature of the bleeding ulcer.[65]

Primary options

esomeprazole: continuous regimen: 80 mg intravenous bolus given over 30 minutes initially, followed by an 8 mg/hour infusion for 72 hours, then switch to oral dose and continue according to local guidelines

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OR

pantoprazole: continuous regimen: 80 mg intravenous bolus given over 30 minutes initially, followed by an 8 mg/hour infusion for 72 hours, then switch to oral dose and continue according to local guidelines

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2nd line – transcatheter arterial embolization (TAE) or surgery

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ACUTE
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active bleeding ulcer
2nd line – 

transcatheter arterial embolization (TAE) or surgery

According to guidelines from the American College of Gastroenterology, patients with bleeding ulcers who have failed endoscopic therapy should next be treated with TAE.[64] Failure of endoscopic therapy may be defined in various ways, including persistent bleeding after initial or subsequent endoscopic therapy and recurrent bleeding after repeat endoscopic therapy.[64] Although surgery is more effective in reducing further bleeding, TAE is associated with markedly fewer complications and is not associated with increased mortality. In clinical practice, surgery may be a better choice for the individual patient when taking into account comorbidities and current medical status as well as local expertise and availability of procedures (e.g., expertise of local interventional radiologists in TAE for upper gastrointestinal bleed and experience of local surgeons in ulcer surgery).[64]

After treatment, the presence of Helicobacter pylori should be assessed, and the patient treated according to guidelines for patients with no active bleeding. 

no active bleeding: Helicobacter pylori negative

1st line – treat underlying cause plus proton-pump inhibitor (PPI)

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ACUTE
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no active bleeding: Helicobacter pylori negative
1st line – 

treat underlying cause plus proton-pump inhibitor (PPI)

Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, should be discontinued, as this is the most likely cause of peptic ulcer in these patients. If this is not possible, or if the patient takes low-dose aspirin for prophylaxis of cardiovascular disease, prophylactic acid inhibitory therapy should be taken long term.[76]

A cyclo-oxygenase (COX-2) inhibitor may be considered in preference to an NSAID to reduce the risk of gastroduodenal toxicity, including ulceration. One large randomized clinical trial found that celecoxib, at moderate doses, was noninferior to ibuprofen and naproxen with regard to cardiovascular safety in patients with arthritis.[77] 

Ulcer healing therapy should then be instituted, typically with a PPI.

Adverse effects of PPI therapy include nausea, diarrhea, and modest increases in gastrin levels.

Treatment course: 4-8 weeks.

Primary options

omeprazole: 20-40 mg orally once daily

OR

lansoprazole: 15-30 mg orally once daily

OR

rabeprazole: 20 mg orally once daily

OR

esomeprazole: 20-40 mg orally once daily

OR

omeprazole/sodium bicarbonate: 20-40 mg orally once daily

More

OR

dexlansoprazole: 30-60 mg orally once daily

2nd line – H2 antagonist or misoprostol

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ACUTE
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no active bleeding: Helicobacter pylori negative
2nd line – 

H2 antagonist or misoprostol

H2 antagonists (e.g., famotidine, nizatidine) are less effective than proton-pump inhibitors, but induce healing in the majority of patients.[78]

Misoprostol is an option for the prevention of NSAID-induced gastric ulcers in patients who need to continue NSAID therapy.[79]

Treatment course: 4-8 weeks.

Primary options

famotidine: 20 mg orally twice daily

OR

nizatidine: 150 mg orally twice daily

Secondary options

misoprostol: 100-200 micrograms orally four times daily

no active bleeding: Helicobacter pylori positive

1st line – H pylori eradication therapy

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ACUTE
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no active bleeding: Helicobacter pylori positive
1st line – 

H pylori eradication therapy

Eradication therapy should not be prescribed without documented infection. If the patient is taking a nonsteroidal anti-inflammatory drug (NSAID) (including aspirin), it should be discontinued if possible. Guidelines recommend that H pylori positive patients taking long-term low-dose aspirin, or a long-term NSAID for arthritis, should be offered eradication therapy.[39][49]​​​​​[50]

The American College of Gastroenterology (ACG) recommends empiric first-line regimens for treatment-naive patients with H pylori infection. Optimized bismuth quadruple therapy consisting of a standard-dose PPI plus bismuth plus tetracycline plus metronidazole for 14 days is the preferred first-line regimen when antibiotic susceptibility is unknown. This regimen may be used in patients with or without a penicillin allergy.[50]

Other regimens that can be considered as first-line for patients with no penicillin allergy include: rifabutin triple therapy (omeprazole plus amoxicillin plus rifabutin) for 14 days; or potassium-competitive acid blocker dual therapy (vonoprazan plus amoxicillin) for 14 days. Potassium-competitive acid blocker triple therapy (vonoprazan plus clarithromycin plus amoxicillin) is another option, but should be avoided in patients with previous exposure to macrolide antibiotics.[48][50]

European guidelines recommend bismuth quadruple therapy as initial treatment in both areas with clarithromycin resistance rates greater or less than 15%. If this treatment fails, levofloxacin triple or quadruple therapy is recommended, followed by clarithromycin triple or quadruple therapy, and if this fails rifabutin triple therapy is recommended. In areas where the clarithromycin resistance rate is known to be 15%, initial therapy can alternatively be started with clarithromycin triple therapy and if it fails the sequence of bismuth quadruple therapy, levofloxacin triple or quadruple therapy, and rifabutin triple therapy is followed. Fourteen days of treatment are recommended.[52]​ 

All regimens contain antibiotics and therefore may cause diarrhea, promote opportunistic infections, and interfere with absorption of many other drugs, including oral contraceptives.

Check for eradication of H pylori with an appropriately conducted urea breath test, fecal antigen test, or biopsy-based test 1 month after the end of therapy.​​​​[50][52] Continuation of acid suppressive therapy after treatment of infection is not necessary in most patients.

To best optimize the management of H pylori infection, eradication therapy should be based on patterns of local and individual antimicrobial resistance, if possible.[81][82]​​​​ However, H pylori culture and molecular testing is not widely available in all countries.[84]

Treatment courses: 14 days

Examples of eradication regimens are provided here. Specific regimens may be available as proprietary combination formulations. However, local guidelines should be consulted to aid selection of an appropriate regimen and determine treatment courses.

Primary options

Bismuth quadruple therapy

omeprazole: 20 mg orally twice daily

or

lansoprazole: 30 mg orally twice daily

or

rabeprazole: 20 mg orally twice daily

or

esomeprazole: 40 mg orally twice daily

-- AND --

bismuth subsalicylate: 300 mg orally four times daily

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-- AND --

metronidazole: 250 mg orally four times daily, or 500 mg orally three to four times daily

-- AND --

tetracycline: 500 mg orally four times daily

OR

Low-dose rifabutin triple therapy

omeprazole/amoxicillin/rifabutin: (10 mg omeprazole/250 mg amoxicillin/12.5 mg rifabutin per capsule) 4 capsules orally every 8 hours for 14 days

OR

Potassium-competitive acid blocker dual therapy

vonoprazan and amoxicillin: 20 mg (vonoprazan) orally twice daily and 1000 mg (amoxicillin) orally three times daily for 14 days

OR

Potassium-competitive acid blocker triple therapy

vonoprazan and amoxicillin and clarithromycin: 20 mg (vonoprazan) orally twice daily and 1000 mg (amoxicillin) orally twice daily and 500 mg (clarithromycin) orally twice daily for 14 days

2nd line – alternative regimen

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ACUTE
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no active bleeding: Helicobacter pylori positive
2nd line – 

alternative regimen

If the first treatment fails, at least one alternative regimen should be tried. Second-line regimens should avoid the antibiotics that were given in the first-line regimen.[48][49]​​

3rd line – acid suppression therapy

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ACUTE
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no active bleeding: Helicobacter pylori positive
3rd line – 

acid suppression therapy

If the organism cannot be eradicated despite repeated attempts, long-term acid suppression therapy may be necessary to control symptoms.

PPIs should only be prescribed for appropriate indications and should be limited to the warranted therapeutic duration of therapy. Based on current data, the overall benefits of PPI treatment significantly outweigh the potential risks in most patients.[95]

Primary options

omeprazole: 20 mg orally once daily

OR

lansoprazole: 15 mg orally once daily

OR

rabeprazole: 20 mg orally once daily

OR

esomeprazole: 20 mg orally once daily

OR

omeprazole/sodium bicarbonate: 20 mg orally once daily

More

OR

dexlansoprazole: 30 mg orally once daily

Secondary options

famotidine: 20 mg orally twice daily

OR

nizatidine: 150 mg orally once daily

ONGOING

frequent recurrences, large or refractory ulcers

1st line – acid suppression therapy

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ONGOING
|
frequent recurrences, large or refractory ulcers
1st line – 

acid suppression therapy

Long-term maintenance acid-suppression therapy may be used in selected high-risk patients (e.g., frequent recurrences, large or refractory ulcers) with or without Helicobacter pylori infection.[85]

The preferred regimen and duration of therapy are uncertain, although most clinicians use a proton-pump inhibitor.

PPIs should only be prescribed for appropriate indications and should be limited to the warranted therapeutic duration of therapy. Based on current data, the overall benefits of PPI treatment significantly outweigh the potential risks in most patients.[95]

Primary options

omeprazole: 20 mg orally once daily

OR

lansoprazole: 15 mg orally once daily

OR

rabeprazole: 20 mg orally once daily

OR

esomeprazole: 20 mg orally once daily

OR

omeprazole/sodium bicarbonate: 20 mg orally once daily

More

OR

dexlansoprazole: 30 mg orally once daily

Secondary options

famotidine: 20 mg orally twice daily

OR

nizatidine: 150 mg orally once daily

NSAID-associated ulcer refractory to acid suppression therapy

1st line – misoprostol

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ONGOING
|
NSAID-associated ulcer refractory to acid suppression therapy
1st line – 

misoprostol

Specifically indicated for nonsteroidal anti-inflammatory drug (NSAID)-associated ulcers.[79]

At effective doses, diarrhea is common and the drug offers no advantage over proton-pump inhibitors, which are generally much better tolerated.

Unknowing or continued use of aspirin or NSAIDs should be ascertained.

Avoid use in pregnancy; can cause abortion, premature birth, uterine rupture, and birth defects.

Primary options

misoprostol: 100-200 micrograms orally four times daily

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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