Peptic ulcer disease

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

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 – urgent evaluation ± blood transfusion

Back

1st line –

urgent evaluation ± blood transfusion

Active gastrointestinal bleeding requires urgent evaluation, with resuscitation and supportive care as appropriate.[64]

For any patient with acute upper gastrointestinal bleeding, use the Blatchford score at first assessment to predict the need for intervention.[56][57][58][59] [ Blatchford Score for Gastrointestinal Bleeding Opens in new window ]

Transfuse any patient with massive bleeding with blood, platelets, and clotting factors in line with local protocols.[56][60]

The British Society of Gastroenterology (BSG) care bundle for acute upper gastrointestinal bleeding recommends giving:[64]
- Red blood cell transfusion if the patient’s haemoglobin is <70 g/L, with a target of 70 to 100 g/L
- Platelets if the patient’s platelet count is ≤50 × 10 ⁹/L.

Patients taking anticoagulation therapy (e.g., warfarin, direct oral anticoagulants [DOACs])

Consider seeking advice from an appropriate specialist if the patient is taking warfarin or a DOAC.

The BSG consensus care bundle for acute upper gastrointestinal bleeding and the 2021 update to the BSG and European Society of Gastrointestinal Endoscopy (ESGE) guideline on endoscopy in patients on antiplatelet or anticoagulant therapy recommend:[50][64]
- Suspending DOACs at presentation and seeking advice from a haematologist when managing patients with severe haemorrhage to weigh up the risks and benefits of the DOAC
- Suspending warfarin at presentation.
  - The BSG consensus care bundle stresses the importance of ensuring a plan is in place for restarting warfarin.[64] Consult a specialist to discuss the risks associated with stopping warfarin and the need for monitoring.[50][64]
In haemodynamically unstable patients, the 2021 update to the BSG and ESGE guideline recommends:[50]
- In patients who are taking warfarin, give intravenous vitamin K and four-factor prothrombin complex concentrate. Fresh frozen plasma can be used if prothrombin complex concentrate is not available.
- If the patient is taking a DOAC, consider the use of reversal agents: idarucizumab in patients taking dabigatran, and andexanet alfa in patients taking anti-factor-Xa. Intravenous four-factor prothrombin complex concentrate can be used if andexanet alfa is not available.
Note that the UK National Institute for Health and Care Excellence (NICE) recommends:[56]
- Prothrombin complex concentrate in patients who are taking warfarin and actively bleeding
- Following local warfarin protocols to treat patients who are taking warfarin and whose upper gastrointestinal bleeding has stopped
- Recombinant factor Vlla (eptacog alfa) when all other methods have failed.

If any medications are temporarily stopped, also seek advice on the appropriate time for these to be re-started. The 2021 update to the BSG and ESGE guideline on endoscopy in patients on antiplatelet or anticoagulant therapy recommends restarting anticoagulation:[50]

As soon as possible after 7 days of anticoagulant interruption in patients with low thrombotic risk.
Preferably within 3 days of anticoagulant interruption in patients with high thrombotic risk, with heparin bridging.

Patients taking aspirin, other non-steroidal anti-inflammatory drugs (NSAIDs), or dual antiplatelet therapy

If the patient is taking aspirin, other NSAIDs (including cyclo-oxygenase-2 [COX-2] inhibitors), or dual antiplatelet therapy:

In general, continue aspirin in the acute phase, if your patient is taking this for secondary prevention.[50][56][59][64][79]
- Consider seeking urgent advice from a specialist if there is major haemorrhage.
  - The National Institute for Health and Care Excellence (NICE) doesn’t make a specific recommendation about major haemorrhage, but advises continuing aspirin only once haemostasis has been achieved.[56]
The BSG consensus care bundle for acute upper gastrointestinal bleeding and the 2021 update to the BSG and ESGE guideline on endoscopy in patients on antiplatelet or anticoagulant therapy recommend continuing aspirin if this is taken as part of dual antiplatelet therapy with a P2Y ₁₂ inhibitor (e.g., clopidogrel, prasugrel, or ticagrelor), and the P2Y ₁₂ is temporarily stopped.[50][64] However, the 2021 update to the BSG and ESGE guideline recommends that, if aspirin is stopped, it should be restarted as soon as haemostasis is achieved or there is no further evidence of haemorrhage.[50]
- The BSG care bundle cites two studies that demonstrate a three-fold increase in the risk of cardiovascular or cerebrovascular events if aspirin, prescribed for secondary prevention, is discontinued.[64][79][80][81]
The 2021 update to the BSG and ESGE guideline recommends considering permanently discontinuing aspirin if the patient is taking it for primary prevention.[50]
If the patient is taking any other NSAIDs (including COX-2 inhibitors), NICE recommends stopping these during the acute phase.[50]
If the patient is taking dual antiplatelet therapy, seek advice from the appropriate specialist to weigh up the benefits and risks of continuing the P2Y ₁₂ inhibitor . Discuss the balance of benefits versus risk with your patient. In general, if the patient:[64]
- Does not have coronary artery stents, the P2Y ₁₂ inhibitor should be stopped temporarily until haemostasis is achieved
- Does have coronary artery stents, dual antiplatelet therapy should ideally be continued due to the high risk of stent thrombosis. However, the risks and benefits of doing so need to be carefully considered by a specialist.

If the ulcer is recurrent or resistant to treatment, the multidisciplinary specialists involved in the patient’s care should balance the risks and benefits of continued antiplatelet therapy.

Do not use tranexamic acid to treat patients with acute gastrointestinal bleeding.[66][67]

Evidence from the HALT-IT trial, in which more than 12,000 patients with severe gastrointestinal bleeding were randomised to tranexamic acid or placebo, showed no improvement in outcomes but increased adverse effects for those who received tranexamic acid.[66][67] [ ]

For further information, see:

Plus – endoscopy

Back

Plus –

endoscopy

Treatment recommended for ALL patients in selected patient group

Most bleeding from peptic ulcers can be treated endoscopically. Endoscopy aids in confirming the diagnosis and identifying the cause of bleeding, as well as stopping the bleeding.

Following resuscitation, patients with severe acute upper gastrointestinal bleeding should undergo upper gastrointestinal endoscopy within 24 hours.[59][69][70][71]
Very early (less than 6 hours from presentation) endoscopy has not been associated with improved patient outcomes, and in some cases can worsen outcome.[59][69][70][71]

Use one of the following methods to achieve haemostatic control of an actively bleeding ulcer:[56][59]

A mechanical method (e.g., clips) with adrenaline (epinephrine)
Thermal coagulation with adrenaline[59][72]
Fibrin or thrombin with adrenaline.

For an ulcer with a non-bleeding visible vessel use:

A mechanical method, thermal coagulation, or fibrin/thrombin as monotherapy or in combination with adrenaline.

Options for persistent refractory bleeding include:

Cap-mounted clips - have been shown to be at least as effective as other more traditional modalities (such as thermal coagulation) for primary haemostasis of peptic ulcer bleeding and are particularly useful for rescue therapy or large (>20 mm) or fibrotic ulcers, or those with a large visible vessel (>2 mm) or located in a high-risk vascular area (e. g., gastroduodenal, left gastric arteries)[59][73][74]
Haemostatic sprays for rescue therapy of uncontrolled bleeding (not for primary haemostasis due to a higher rate of rebleeding than with more definitive methods).[75][76]

Do not use adrenaline as monotherapy for the endoscopic treatment of non-variceal upper gastrointestinal bleeding.[56]

After endoscopy, assess for the presence of Helicobacter pylori and treat the patient according to the guidelines for patients with no active bleeding.

Use the full Rockall score after endoscopy to estimate the risk of rebleeding or death.[65] [ Rockall Score for Upper Gastrointestinal Bleeding Opens in new window ]

If the patient re-bleeds after their initial endoscopy, repeat the endoscopy and treat endoscopically or with emergency surgery.[56]

Consider – proton-pump inhibitor (PPI)

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Consider –

proton-pump inhibitor (PPI)

Additional treatment recommended for SOME patients in selected patient group

After endoscopy, prescribe a PPI to any patient who had endoscopic evidence of recent haemorrhage.[56][61] Some centres use a high-dose oral PPI, but the standard approach remains an intravenous infusion for 72 hours, followed by a switch to oral administration.[61] In practice, continue the PPI for 6 to 8 weeks irrespective of H pylori status. If on long-term NSAID or aspirin, with no way of stopping this, continue long-term PPI prophylaxis.

The role of pre-endoscopic PPI therapy in patients who present with ulcer bleeding remains an area of ongoing debate.[56][77] The UK National Institute for Health and Care Excellence (NICE) recommends that acid-suppression drugs (i.e., PPIs or H2 antagonists) should not be offered before endoscopy because of a lack of evidence to show improved outcomes.[56] International consensus recommendations state that pre-endoscopic PPI therapy can be considered on the basis that it may downstage the lesion or reduce the need for endoscopic haemostatic treatment, although it should not delay endoscopy.[77]

Primary options

omeprazole: 80 mg intravenously initially over 40-60 minutes, followed by 8 mg/hour intravenous infusion for 72 hours, then switch to oral therapy

esomeprazole: 80 mg intravenously initially over 30 minutes, followed by 8 mg/hour intravenous infusion for 72 hours, then switch to oral therapy

2nd line – repeat endoscopy or embolisation via interventional radiology or surgery

no active bleeding: Helicobacter pylori negative

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

2nd line – H2 antagonist

no active bleeding: Helicobacter pylori positive

no long-term use of non-steroidal anti-inflammatory drugs or low-dose aspirin

1st line – H pylori eradication therapy

Back

1st line –

H pylori eradication therapy

Eradication regimens vary between guidelines and locations; traditional empirical ‘triple therapies’ rarely achieve satisfactory eradication rates and success rates vary according to local and regional resistance patterns.[86] Empirical therapies should be restricted to those shown to be highly effective locally.[87] Check local guidance and follow local protocols.

Eradication therapy leads to ulcer healing and a dramatic decrease in ulcer recurrence.[84] [ ] [ ] Most regimens are 70% to 90% efficacious in practice, limited mainly by antibiotic resistance or patient adherence to the regimen.
Check the patient’s antibiotic history and allergy status, and stress the importance of adherence.
To optimise the management of H pylori infection, base eradication therapy on patterns of local and individual antimicrobial resistance, if possible.[106][107]
Offer people with peptic ulcer (gastric or duodenal) and proven H pylori retesting for H pylori 6 to 8 weeks after beginning treatment, depending on the size of the lesion.

The regimens below are based on guidance from the UK’s National Institute for Health and Care Excellence (NICE) and Public Health England but will often need to be substituted with local protocols that take account of resistance patterns because traditional empirical 'triple therapies' often fail to achieve successful eradication.[46][48]

For eradication therapy, prescribe triple therapy (a proton-pump inhibitor [PPI] plus two antibiotics) first-line.[46]

A PPI plus amoxicillin plus either clarithromycin or metronidazole is the recommended first-line treatment option.[46][48]
In patients who are allergic to penicillin, first-line triple therapy consists of a PPI plus clarithromycin plus metronidazole.[46][48]
If patients who are allergic to penicillin have had previous clarithromycin exposure, give quadruple therapy with a PPI plus bismuth plus metronidazole plus tetracycline.[46][48]
Treatment course: 7 days.

Re-test patients with peptic ulcer (gastric or duodenal) and who were initially H pylori positive, 6 to 8 weeks after beginning treatment, depending on the size of the lesion.[46]

Leave a 2-week washout period after PPI use and a 4-week washout after antibiotic use before re-testing for H pylori with a breath test, as these drugs suppress bacteria and can lead to false negatives.[46][48]

In practice, in most patients, you will not need to continue long-term acid suppressive therapy after treatment of H pylori infection.

All regimens contain antibiotics and therefore may cause diarrhoea, promote opportunistic infections, and interfere with absorption of many other drugs, including oral contraceptives. If diarrhoea develops, consider microscopic colitis (lymphocytic or collagenous colitis) and, more rarely, Clostridium difficile-associated disease. Review the need for treatment.[48]

Primary options

No penicillin allergy

esomeprazole: 20 mg orally twice daily

lansoprazole: 30 mg orally twice daily

omeprazole: 20-40 mg orally twice daily

pantoprazole: 40 mg orally twice daily

rabeprazole: 20 mg orally twice daily

-- AND --

amoxicillin: 1000 mg orally twice daily

-- AND --

clarithromycin: 500 mg orally (immediate-release) twice daily

metronidazole: 400 mg orally twice daily

Penicillin allergy with no previous clarithromycin exposure

esomeprazole: 20 mg orally twice daily

lansoprazole: 30 mg orally twice daily

omeprazole: 20-40 mg orally twice daily

pantoprazole: 40 mg orally twice daily

rabeprazole: 20 mg orally twice daily

-- AND --

clarithromycin: 500 mg orally (immediate-release) twice daily

-- AND --

metronidazole: 400 mg orally twice daily

Penicillin allergy with previous clarithromycin exposure

esomeprazole: 20 mg orally twice daily

lansoprazole: 30 mg orally twice daily

omeprazole: 20-40 mg orally twice daily

pantoprazole: 40 mg orally twice daily

rabeprazole: 20 mg orally twice daily

-- AND --

bismuth subsalicylate: 525 mg orally four times daily

-- AND --

tetracycline: 500 mg orally four times daily

-- AND --

metronidazole: 400 mg orally twice daily

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Show drug information for a patient with no comorbidities

Primary options

No penicillin allergy

esomeprazole

lansoprazole

omeprazole

pantoprazole

rabeprazole

-- AND --

amoxicillin

-- AND --

clarithromycin

metronidazole

Penicillin allergy with no previous clarithromycin exposure

esomeprazole

lansoprazole

omeprazole

pantoprazole

rabeprazole

-- AND --

clarithromycin

-- AND --

metronidazole

Penicillin allergy with previous clarithromycin exposure

esomeprazole

lansoprazole

omeprazole

pantoprazole

rabeprazole

-- AND --

bismuth subsalicylate

-- AND --

tetracycline

-- AND --

metronidazole

Consider – ulcer healing therapy

2nd line – alternative H pylori eradication regimen

Back

2nd line –

alternative H pylori eradication regimen

If the first eradication treatment fails, try an alternative 7-day triple regimen.[46]

Use a PPI plus amoxicillin plus either clarithromycin or metronidazole ( whichever was not used first-line).[46][48]

If a patient has had previous exposure to clarithromycin and metronidazole offer a course of treatment with a PPI plus amoxicillin plus tetracycline (or, if a tetracycline cannot be used, levofloxacin).[46][48]
Offer people who are allergic to penicillin (and who have not had previous exposure to a fluoroquinolone antibiotic) a course of treatment with a PPI plus metronidazole plus levofloxacin.[46][48]
Offer people who are allergic to penicillin and who have had previous exposure to a fluoroquinolone antibiotic, a course of a PPI plus bismuth plus metronidazole plus tetracycline.[46]

Drug safety alert: Restrictions on the use of fluoroquinolone antibiotics

Fluoroquinolones are associated with serious, disabling, and potentially irreversible adverse effects including tendonitis, tendon rupture, arthralgia, neuropathies, and other musculoskeletal or nervous system effects. The European Medicines Agency recommends that fluoroquinolone antibiotics be restricted for use in serious, life-threatening bacterial infections only. Furthermore, they recommend that fluoroquinolones should not be used for mild to moderate infections unless other appropriate antibiotics for the specific infection cannot be used, and should not be used in non-severe, non-bacterial, or self-limiting infections. The UK-based Medicines and Healthcare products Regulatory Agency (MHRA) supports these recommendations.[108][109]

In areas with high rates of multiple drug resistance, pre-treatment antimicrobial susceptibility-guided therapy may be more effective than clarithromycin-based triple therapy alone for H pylori eradication.[107] However, H pylori culture and molecular testing is not widely available in all countries.[110]

Primary options

No penicillin allergy with no previous exposure to clarithromycin or metronidazole

esomeprazole: 20 mg orally twice daily

lansoprazole: 30 mg orally twice daily

omeprazole: 20-40 mg orally twice daily

pantoprazole: 40 mg orally twice daily

rabeprazole: 20 mg orally twice daily

-- AND --

amoxicillin: 1000 mg orally twice daily

-- AND --

clarithromycin: 500 mg orally (immediate-release) twice daily

metronidazole: 400 mg orally twice daily

No penicillin allergy with previous exposure to clarithromycin and metronidazole

esomeprazole: 20 mg orally twice daily

lansoprazole: 30 mg orally twice daily

omeprazole: 20-40 mg orally twice daily

pantoprazole: 40 mg orally twice daily

rabeprazole: 20 mg orally twice daily

-- AND --

amoxicillin: 1000 mg orally twice daily

-- AND --

tetracycline: 500 mg orally four times daily

levofloxacin: 250 mg orally twice daily

Penicillin allergy with no previous fluoroquinolone exposure

esomeprazole: 20 mg orally twice daily

lansoprazole: 30 mg orally twice daily

omeprazole: 20-40 mg orally twice daily

pantoprazole: 40 mg orally twice daily

rabeprazole: 20 mg orally twice daily

-- AND --

metronidazole: 400 mg orally twice daily

-- AND --

levofloxacin: 250 mg orally twice daily

Penicillin allergy with previous fluoroquinolone exposure

esomeprazole: 20 mg orally twice daily

lansoprazole: 30 mg orally twice daily

omeprazole: 20-40 mg orally twice daily

pantoprazole: 40 mg orally twice daily

rabeprazole: 20 mg orally twice daily

-- AND --

bismuth subsalicylate: 525 mg orally four times daily

-- AND --

tetracycline: 500 mg orally four times daily

-- AND --

metronidazole: 400 mg orally twice daily

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Show drug information for a patient with no comorbidities

Primary options

No penicillin allergy with no previous exposure to clarithromycin or metronidazole

esomeprazole

lansoprazole

omeprazole

pantoprazole

rabeprazole

-- AND --

amoxicillin

-- AND --

clarithromycin

metronidazole

No penicillin allergy with previous exposure to clarithromycin and metronidazole

esomeprazole

lansoprazole

omeprazole

pantoprazole

rabeprazole

-- AND --

amoxicillin

-- AND --

tetracycline

levofloxacin

Penicillin allergy with no previous fluoroquinolone exposure

esomeprazole

lansoprazole

omeprazole

pantoprazole

rabeprazole

-- AND --

metronidazole

-- AND --

levofloxacin

Penicillin allergy with previous fluoroquinolone exposure

esomeprazole

lansoprazole

omeprazole

pantoprazole

rabeprazole

-- AND --

bismuth subsalicylate

-- AND --

tetracycline

-- AND --

metronidazole

3rd line – referral to specialist service

with long-term use of non-steroidal anti-inflammatory drugs or low-dose aspirin

1st line – ulcer healing therapy

Back

1st line –

ulcer healing therapy

If the H pylori positive patient is a long-term user of NSAIDs (or low-dose aspirin):[46]

Discontinue any NSAID the patient is taking, if possible.[46] If this is not possible, and in people at high risk (previous ulceration), consider a COX-2 inhibitor instead of a standard NSAID and prescribe a PPI.[46]
- Weigh up the benefits versus risks of reducing or stopping any other potential ulcer-inducing drugs, including aspirin.[83] Seek senior/specialist advice if low-dose aspirin is being taken for secondary prevention of cardiovascular or cerebrovascular events as the benefits of continuing may need to take priority.[79]
NICE recommends to:
- Start ulcer healing therapy with a full-dose proton-pump inhibitor [PPI] or H2 antagonist for 8 weeks.[46]
- Then offer H pylori eradication therapy (typically a 7-day course of triple therapy [PPI + two antibiotics]).[46] See H pylori eradication therapy below.

In practice, a specialist may advise eradication therapy before ulcer healing therapy or vice-versa based on their clinical experience and preference. Always follow your local protocols and use your clinical judgment to determine the optimal approach for your individual patient.

Primary options

esomeprazole: 20 mg orally once daily

lansoprazole: 30 mg orally once daily

omeprazole: 20 mg orally once daily

pantoprazole: 40 mg orally once daily

rabeprazole: 20 mg orally once daily

Secondary options

famotidine: 40 mg orally once daily at night

nizatidine: 300 mg orally once daily at night

Plus – H pylori eradication therapy

Back

Plus –

H pylori eradication therapy

Treatment recommended for ALL patients in selected patient group

Eradication therapy leads to ulcer healing and a dramatic decrease in ulcer recurrence.[84] [ ] [ ] Most regimens are 70% to 90% efficacious in practice, limited mainly by antibiotic resistance or patient adherence to the regimen.
Check the patient’s antibiotic history and allergy status, and stress the importance of adherence.
To optimise the management of H pylori infection, base eradication therapy on patterns of local and individual antimicrobial resistance, if possible.[106][107]
Offer people with peptic ulcer (gastric or duodenal) and proven H pylori retesting for H pylori 6 to 8 weeks after beginning treatment, depending on the size of the lesion.[46]

Offer 7 days of H pylori eradication therapy to people who have tested positive for H pylori and who have peptic ulcer disease.[46]

For eradication therapy, prescribe triple therapy (a proton-pump inhibitor [PPI] plus two antibiotics) first-line.[46]

A PPI plus amoxicillin plus either clarithromycin or metronidazole is the recommended first-line treatment option.[46][48]
In patients who are allergic to penicillin, first-line triple therapy consists of a PPI plus clarithromycin plus metronidazole.[46][48]
If patients who are allergic to penicillin have had previous clarithromycin exposure, give quadruple therapy with a PPI plus bismuth plus metronidazole plus tetracycline.[46][48]
Treatment course: 7 days.

Re-test patients with peptic ulcer (gastric or duodenal) and who were initially H pylori positive, 6 to 8 weeks after beginning treatment, depending on the size of the lesion.[46]

Leave a 2-week washout period after PPI use and a 4-week washout after antibiotic use before re-testing for H pylori with a breath test, as these drugs suppress bacteria and can lead to false negatives.[46][48]

In practice, in most patients, you will not need to continue long-term acid suppressive therapy after treatment of H pylori infection.

Primary options

No penicillin allergy

esomeprazole: 20 mg orally twice daily

lansoprazole: 30 mg orally twice daily

omeprazole: 20-40 mg orally twice daily

pantoprazole: 40 mg orally twice daily

rabeprazole: 20 mg orally twice daily

-- AND --

amoxicillin: 1000 mg orally twice daily

-- AND --

clarithromycin: 500 mg orally (immediate-release) twice daily

metronidazole: 400 mg orally twice daily

Penicillin allergy with no previous clarithromycin exposure

esomeprazole: 20 mg orally twice daily

lansoprazole: 30 mg orally twice daily

omeprazole: 20-40 mg orally twice daily

pantoprazole: 40 mg orally twice daily

rabeprazole: 20 mg orally twice daily

-- AND --

clarithromycin: 500 mg orally (immediate-release) twice daily

-- AND --

metronidazole: 400 mg orally twice daily

Penicillin allergy with previous clarithromycin exposure

esomeprazole: 20 mg orally twice daily

lansoprazole: 30 mg orally twice daily

omeprazole: 20-40 mg orally twice daily

pantoprazole: 40 mg orally twice daily

rabeprazole: 20 mg orally twice daily

-- AND --

bismuth subsalicylate: 525 mg orally four times daily

-- AND --

tetracycline: 500 mg orally four times daily

-- AND --

metronidazole: 400 mg orally twice daily

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Show drug information for a patient with no comorbidities

Primary options

No penicillin allergy

esomeprazole

lansoprazole

omeprazole

pantoprazole

rabeprazole

-- AND --

amoxicillin

-- AND --

clarithromycin

metronidazole

Penicillin allergy with no previous clarithromycin exposure

esomeprazole

lansoprazole

omeprazole

pantoprazole

rabeprazole

-- AND --

clarithromycin

-- AND --

metronidazole

Penicillin allergy with previous clarithromycin exposure

esomeprazole

lansoprazole

omeprazole

pantoprazole

rabeprazole

-- AND --

bismuth subsalicylate

-- AND --

tetracycline

-- AND --

metronidazole

2nd line – alternative H pylori eradication regimen

Back

2nd line –

alternative H pylori eradication regimen

If the first eradication treatment fails, try an alternative 7-day triple regimen.[46]

Use a PPI plus amoxicillin plus either clarithromycin or metronidazole ( whichever was not used first-line).[46][48]

If a patient has had previous exposure to clarithromycin and metronidazole offer a course of treatment with a PPI plus amoxicillin plus tetracycline (or, if a tetracycline cannot be used, levofloxacin).[46][48]
Offer people who are allergic to penicillin (and who have not had previous exposure to a fluoroquinolone antibiotic) a course of treatment with a PPI plus metronidazole plus levofloxacin.[46][48]
Offer people who are allergic to penicillin and who have had previous exposure to a fluoroquinolone antibiotic, a course of a PPI plus bismuth plus metronidazole plus tetracycline.[46]

Drug safety alert: Restrictions on the use of fluoroquinolone antibiotics

Primary options

No penicillin allergy with no previous exposure to clarithromycin or metronidazole

esomeprazole: 20 mg orally twice daily

lansoprazole: 30 mg orally twice daily

omeprazole: 20-40 mg orally twice daily

pantoprazole: 40 mg orally twice daily

rabeprazole: 20 mg orally twice daily

-- AND --

amoxicillin: 1000 mg orally twice daily

-- AND --

clarithromycin: 500 mg orally (immediate-release) twice daily

metronidazole: 400 mg orally twice daily

No penicillin allergy with previous exposure to clarithromycin and metronidazole

esomeprazole: 20 mg orally twice daily

lansoprazole: 30 mg orally twice daily

omeprazole: 20-40 mg orally twice daily

pantoprazole: 40 mg orally twice daily

rabeprazole: 20 mg orally twice daily

-- AND --

amoxicillin: 1000 mg orally twice daily

-- AND --

tetracycline: 500 mg orally four times daily

levofloxacin: 250 mg orally twice daily

Penicillin allergy with no previous fluoroquinolone exposure

esomeprazole: 20 mg orally twice daily

lansoprazole: 30 mg orally twice daily

omeprazole: 20-40 mg orally twice daily

pantoprazole: 40 mg orally twice daily

rabeprazole: 20 mg orally twice daily

-- AND --

metronidazole: 400 mg orally twice daily

-- AND --

levofloxacin: 250 mg orally twice daily

Penicillin allergy with previous fluoroquinolone exposure

esomeprazole: 20 mg orally twice daily

lansoprazole: 30 mg orally twice daily

omeprazole: 20-40 mg orally twice daily

pantoprazole: 40 mg orally twice daily

rabeprazole: 20 mg orally twice daily

-- AND --

bismuth subsalicylate: 525 mg orally four times daily

-- AND --

tetracycline: 500 mg orally four times daily

-- AND --

metronidazole: 400 mg orally twice daily

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Show drug information for a patient with no comorbidities

Primary options

No penicillin allergy with no previous exposure to clarithromycin or metronidazole

esomeprazole

lansoprazole

omeprazole

pantoprazole

rabeprazole

-- AND --

amoxicillin

-- AND --

clarithromycin

metronidazole

No penicillin allergy with previous exposure to clarithromycin and metronidazole

esomeprazole

lansoprazole

omeprazole

pantoprazole

rabeprazole

-- AND --

amoxicillin

-- AND --

tetracycline

levofloxacin

Penicillin allergy with no previous fluoroquinolone exposure

esomeprazole

lansoprazole

omeprazole

pantoprazole

rabeprazole

-- AND --

metronidazole

-- AND --

levofloxacin

Penicillin allergy with previous fluoroquinolone exposure

esomeprazole

lansoprazole

omeprazole

pantoprazole

rabeprazole

-- AND --

bismuth subsalicylate

-- AND --

tetracycline

-- AND --

metronidazole

3rd line – referral to specialist service

ONGOING

recurrent or refractory ulcers

1st line – long-term acid suppression therapy

Back

1st line –

long-term 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 H pylori infection. The preferred regimen and duration of therapy are uncertain, although most clinicians use a proton-pump inhibitor (PPI).

If the organism cannot be eradicated despite repeated attempts, long-term acid suppression therapy may be necessary to control symptoms and prevent relapse.
If symptoms continue or recur after initial treatment, prescribe a PPI or H2 antagonist at the lowest dose that controls symptoms.[46]

Encourage patients to manage their own symptoms by using PPI treatment on an 'as-needed' basis.[46]

Based on current data, the overall benefits of PPI treatment outweigh the potential risks in most patients.[97] However, various studies have suggested an association, though not necessarily a causal link, between long-term use of PPIs and increased risk of:[88][91][92][93]

Osteoporosis[89][98]
Pneumonia
Dementia
Stroke
Type 2 diabetes[96]
Enteric infection.[97]

Drug safety alert: Adverse events associated with long-term use of PPIs

Severe hypomagnesaemia has been reported infrequently in patients treated with PPIs, rarely after 3 months, but usually after 1 year of treatment. Serious features of hypomagnesaemia include fatigue, tetany, delirium, convulsions, dizziness, and ventricular arrhythmia. Hypomagnesaemia usually improves after magnesium replacement and discontinuation of the PPI.[102]

PPIs have been associated with an increased risk of osteoporosis and a modest increase in the risk of hip, wrist, or spine fracture, especially if used by older people in high doses and for >1 year.[103]

PPIs have been linked rarely, but probably causally, to subacute cutaneous lupus erythematosus (SCLE).[104]

In being vigilant for these rare adverse events:

Consider measuring magnesium levels before starting PPI treatment and periodically during prolonged treatment, especially in those who take concomitant digoxin or drugs that may cause hypomagnesaemia (e.g., diuretics).[102]
Treat patients at risk of osteoporosis according to current clinical guidelines to ensure they have an adequate intake of vitamin D and calcium.[103]
Advise patients who develop arthralgia and skin lesions in sun-exposed areas to avoid sunlight, and consider giving topical or systemic corticosteroids if there are no signs of remission after a few weeks or months.[104]
Consider stopping the PPI unless it is imperative for a serious acid-related condition.
Take into account any use of PPIs obtained over-the-counter.

Offer H2 antagonist therapy if there is an inadequate response to a PPI.[46]

In people with an unhealed ulcer, exclude non-adherence, malignancy, failure to detect H pylori, inadvertent or surreptitious NSAID use, other ulcer-inducing medication, and rare causes such as Zollinger–Ellison syndrome or Crohn's disease.[46]

In people at high risk (previous ulceration) and for whom NSAID continuation is necessary, consider a cyclo-oxygenase-2 (COX-2) inhibitor instead of a standard NSAID. In either case, prescribe with a PPI.[46]

Discuss the potential harm associated with NSAIDs with patients who continue to take them after a peptic ulcer has healed.[46]

Review the need for NSAID use regularly (at least every 6 months)
Offer a trial of NSAID use on a limited 'as needed' basis[46]
Consider:[46]
- Reducing the NSAID dose
- Substituting the NSAID with paracetamol
- Using an alternative analgesic
- Using low-dose ibuprofen.

Primary options

esomeprazole: 10 mg orally once daily

lansoprazole: 15 mg orally once daily

omeprazole: 10 mg orally once daily

pantoprazole: 20 mg orally once daily

rabeprazole: 10 mg orally once daily

Secondary options

famotidine: 20 mg orally once daily at night

nizatidine: 150 mg orally once daily at night

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Peptic ulcer disease

Treatment algorithm

active bleeding ulcer

urgent evaluation ± blood transfusion

endoscopy

proton-pump inhibitor (PPI)

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

repeat endoscopy or embolisation via interventional radiology or surgery

no active bleeding: Helicobacter pylori negative

treat underlying cause plus proton-pump inhibitor (PPI)

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

H2 antagonist

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

no active bleeding: Helicobacter pylori positive

no long-term use of non-steroidal anti-inflammatory drugs or low-dose aspirin

H pylori eradication therapy

Primary options

No penicillin allergy

Penicillin allergy with no previous clarithromycin exposure

Penicillin allergy with previous clarithromycin exposure

These drug options and doses relate to a patient with no comorbidities.

Primary options

No penicillin allergy

Penicillin allergy with no previous clarithromycin exposure

Penicillin allergy with previous clarithromycin exposure

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

No penicillin allergy

Penicillin allergy with no previous clarithromycin exposure

Penicillin allergy with previous clarithromycin exposure

ulcer healing therapy

Primary options

Secondary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Secondary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

Secondary options

alternative H pylori eradication regimen

Drug safety alert: Restrictions on the use of fluoroquinolone antibiotics

Primary options

No penicillin allergy with no previous exposure to clarithromycin or metronidazole

No penicillin allergy with previous exposure to clarithromycin and metronidazole

Penicillin allergy with no previous fluoroquinolone exposure

Penicillin allergy with previous fluoroquinolone exposure

These drug options and doses relate to a patient with no comorbidities.

Primary options

No penicillin allergy with no previous exposure to clarithromycin or metronidazole

No penicillin allergy with previous exposure to clarithromycin and metronidazole

Penicillin allergy with no previous fluoroquinolone exposure

Penicillin allergy with previous fluoroquinolone exposure

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

No penicillin allergy with no previous exposure to clarithromycin or metronidazole

No penicillin allergy with previous exposure to clarithromycin and metronidazole

Penicillin allergy with no previous fluoroquinolone exposure

Penicillin allergy with previous fluoroquinolone exposure

referral to specialist service

with long-term use of non-steroidal anti-inflammatory drugs or low-dose aspirin

ulcer healing therapy

Primary options

Secondary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Secondary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options