Dyspepsia and Peptic Ulcer Disease

Clinical Snapshot

Dyspepsia is pain or discomfort centred in the upper abdomen, often accompanied by nausea, early satiety, fullness, or bloating. It is distinct from heartburn and regurgitation, which are symptoms of gastroesophageal reflux disease rather than dyspepsia. Dyspepsia is the cardinal symptom of peptic ulcer disease (PUD) — a break in the mucosa of the stomach (gastric ulcer) or proximal duodenum (duodenal ulcer) — but most patients investigated for chronic dyspepsia have a normal endoscopy; this group is termed functional dyspepsia (FD), further split into epigastric pain syndrome (EPS, pain not clearly related to meals) and postprandial distress syndrome (PDS, discomfort or fullness after eating).^[1] The two dominant causes of PUD are Helicobacter pylori infection and NSAID or ASA use (including low-dose ASA for cardiovascular prophylaxis) — a meaningful minority of ulcers occur without either cause identified. Because PUD and functional dyspepsia cannot be reliably distinguished by symptoms alone, initial management of uninvestigated dyspepsia follows a structured test-and-treat/empiric-therapy pathway rather than attempting to guess the underlying cause clinically.^[2]

Recognize the Condition

Uninvestigated dyspepsia

Epigastric pain or discomfort lasting at least one month, often with associated fullness, early satiety, nausea, or bloating. Duodenal ulcer pain classically improves with food and recurs 2-3 hours after eating or at night; gastric ulcer pain is more often worsened by food. In practice this pattern is unreliable for distinguishing PUD from functional dyspepsia and should not be relied upon diagnostically.

Peptic ulcer disease

May present with epigastric pain as above, or entirely silently — this is common with NSAID-induced ulcers, which frequently present for the first time with a bleeding or perforation complication rather than antecedent pain. Physical examination is usually normal or shows only mild epigastric tenderness; a normal exam does not exclude PUD.

Functional dyspepsia subtypes (Rome IV)

Epigastric pain syndrome (EPS)

Upper abdominal pain or burning not distinctly related to meals.

Postprandial distress syndrome (PDS)

Bothersome postprandial fullness or early satiety, typically worse with meals.

The two subtypes commonly overlap in the same patient and both are diagnoses of exclusion made only after endoscopy (or empiric management, in patients under 60 without alarm features) has not identified an organic explanation.^[1]

Risk Factors

Helicobacter pylori infection — the single most common identifiable cause of PUD worldwide.
NSAID use, including over-the-counter formulations, and low-dose ASA for cardiovascular prophylaxis.
Concomitant use of corticosteroids, antiplatelet agents (clopidogrel, ticagrelor), anticoagulants (warfarin, direct oral anticoagulants), or SSRIs alongside an NSAID or ASA — each additive to ulcer/bleeding risk.
Age over 65, and especially over 70.
High-dose or multiple concurrent NSAIDs.
Prior history of gastric or duodenal ulcer or upper GI bleeding.
Severe medical comorbidity — heart failure, COPD, chronic renal or hepatic disease, advanced malignancy.
Smoking.
Other medications that can cause or aggravate dyspepsia: bisphosphonates, calcium channel blockers, erythromycin and other macrolides, iron salts, metronidazole, tetracyclines, and opioids (particularly codeine).
For functional dyspepsia specifically: female sex, smoking, and an overlying anxiety or mood disorder are each associated, though a specific cause is often not identifiable.

Red Flags & Refer

Any dyspepsia patient 60 years of age or older with new-onset symptoms should have upper endoscopy to exclude upper GI neoplasia. Below age 60, alarm features should not automatically trigger endoscopy — current guideline evidence is only moderate quality for this age group — but each of the following still warrants case-by-case clinical judgment and a lower threshold to investigate or refer, especially when more than one is present.^[2]

Evidence of GI bleeding — hematemesis, melena, or occult blood on testing.
Unintentional weight loss.
Dysphagia or odynophagia.
Iron-deficiency anemia.
Persistent or recurrent vomiting.
A palpable abdominal mass or lymphadenopathy.
Jaundice.
Family history of upper GI malignancy, or childhood spent in a country with a high incidence of gastric cancer — consider endoscopy at a younger age than 60 in these patients.
Unrelenting upper abdominal pain radiating to the back, especially with weight loss or jaundice — consider imaging for pancreatic pathology rather than assuming uncomplicated dyspepsia.

Assessment & Diagnosis

Dyspepsia versus GERD — differentiating on presentation

Feature	Dyspepsia	GERD (managed separately, not in this chapter)
Primary symptom	Epigastric pain or discomfort, fullness, early satiety, bloating, nausea	Heartburn (retrosternal burning) and regurgitation
Relation to position	Not typically positional	Often worse lying flat or bending over
Typical trigger	Meals (variably improves or worsens symptoms depending on subtype)	Meals, especially large or fatty meals; worse at night
Overlap	Some patients with GERD report epigastric pain as a predominant symptom, which can look like dyspepsia	Some dyspepsia patients report incidental heartburn

History

Exclude non-GI sources of upper abdominal pain — ischemic heart disease, biliary or pancreatic disease, pulmonary disease.
Full medication history, including OTC, herbal, and supplement use, focused specifically on NSAID/ASA use (including low-dose ASA) and the other dyspepsia-aggravating drugs listed under Risk Factors.
Screen explicitly for every alarm feature above at every assessment, not only at the first visit.

When endoscopy is and is not indicated

Endoscopy is indicated for any new-onset dyspepsia at age 60 or older, and should be considered case-by-case below that age when alarm features are present.^[2] Endoscopy allows direct visualization and biopsy and is the most sensitive and specific test available, but is not required to initiate management in a younger patient without alarm features — that patient should proceed directly to the test-and-treat/empiric-therapy pathway described in Choose Initial Treatment. Upper GI barium studies are not recommended for investigating dyspepsia given a substantial false-positive and false-negative rate; Choosing Wisely Canada specifically recommends against this test for this indication.

H. pylori testing

Urea breath test (UBT) — highly sensitive and specific; the preferred non-invasive test where available. Requires stopping antibiotics/bismuth for 4 weeks and PPIs/H2RAs for at least 1-2 weeks beforehand to avoid a false negative.^[3]
Fecal (stool) antigen test — comparably accurate to UBT, requires a stool sample, and is similarly affected by recent acid-suppressive therapy.^[3]
Serology (IgG) — appropriate only when there has been no prior eradication attempt; not affected by recent PPI/antibiotic use, but cannot be used to confirm eradication since it can remain positive for years after successful treatment.
Endoscopic biopsy (rapid urease test, histology) — the gold-standard invasive option; reserved for patients already undergoing endoscopy for another indication rather than performed solely for H. pylori diagnosis.

All patients diagnosed with PUD — regardless of NSAID/ASA use — should be tested for H. pylori and treated if positive.^[4]

Treatment Targets

Relieve and prevent symptoms of dyspepsia.
Confirm and eradicate H. pylori as a potential underlying cause.
Heal active PUD and prevent its recurrence.
Prevent PUD-related complications — bleeding, perforation, obstruction — in patients on ongoing ASA or NSAID therapy.
Confirm H. pylori eradication with the correct test at the correct interval whenever eradication was attempted.
Avoid indefinite, unreviewed PPI therapy once the original indication has resolved.

Choose Initial Treatment

Direct treatment rule

Endoscopy versus empiric management

Age 60 or older, new-onset dyspepsia refer for upper endoscopy before starting empiric therapy.

Under 60, no alarm features proceed directly to H. pylori test-and-treat as the first step — do not wait for or require endoscopy first.^[2]

Uninvestigated dyspepsia under age 60

1st step non-invasive H. pylori testing (UBT or stool antigen preferred); treat with an eradication regimen if positive.^[2]

If H. pylori-negative, or symptoms persist after confirmed successful eradication a 4-8 week empiric trial of standard-dose PPI therapy.

If PPI and H. pylori eradication have both failed to control symptoms a trial of a prokinetic agent or a low-dose tricyclic antidepressant — either may be tried first; there is no strong evidence favouring one sequence over the other.

Functional dyspepsia (confirmed by endoscopy showing no organic pathology)

H. pylori positive treat the infection regardless of whether eradication is expected to fully resolve symptoms.

H. pylori negative, or symptomatic despite eradication standard-dose PPI trial.

PPI and H. pylori eradication (if applicable) have both failed a tricyclic antidepressant, then a prokinetic agent if the TCA also fails, then psychological therapy (e.g., cognitive behavioural therapy) if drug therapy overall fails — in that order.^[2]

H. pylori eradication regimen selection

1st line, all treatment-naive patients 14-day optimized bismuth quadruple therapy — the current preferred regimen given rising clarithromycin resistance.^[4]

Reasonable alternative first-line options 14-day rifabutin triple therapy, or PCAB (vonoprazan)-amoxicillin dual therapy where locally available.

Do not use clarithromycin-containing triple therapy empirically — reserve it strictly for patients with confirmed clarithromycin susceptibility, since empiric use now fails in a large proportion of patients given resistance rates that regularly exceed 15-30% in North America.^[4]

NSAID/ASA-associated ulcer prevention and treatment

Moderate-to-high GI risk patient requiring ongoing NSAID or ASA therapy co-prescribe a once-daily PPI for the duration of NSAID/ASA use.^[5]

Active PUD in a patient using ASA or an NSAID stop the NSAID when possible and treat with a standard-dose PPI; continue low-dose ASA for cardiovascular prophylaxis if indicated, but continue the PPI for as long as ASA continues.^[6]

Non-Pharmacologic Treatment

Advise moderation of foods/beverages that reproducibly worsen symptoms — coffee, orange juice, alcohol, spicy or fatty foods, large meals, or eating on the run.
Recommend avoiding non-prescription products containing ASA or NSAIDs, which can cause or worsen both dyspepsia and PUD.
Eating smaller, more frequent meals and reducing high-fat food intake can help functional dyspepsia, particularly postprandial distress syndrome.
Reassure and educate functional dyspepsia patients about the benign nature of the condition — this itself has therapeutic value, since anxiety about a missed serious diagnosis can perpetuate symptoms.
Refer for psychological therapy (e.g., cognitive behavioural therapy) when there is an overlying mood or anxiety disorder, or when functional dyspepsia has not responded to sequential drug therapy.
Smoking cessation counselling.

Pharmacologic Treatment Options

H. pylori eradication regimen tracks

Bismuth quadruple therapy — 1st line

PPI BID + bismuth + tetracycline 500 mg QID + metronidazole 500 mg TID-QID, for 14 days. Preferred for all treatment-naive patients given current clarithromycin resistance rates.^[4]

Rifabutin triple therapy — 1st-line alternative or salvage

PPI BID + amoxicillin 1 g TID + rifabutin (capped at 150 mg/day), for 14 days. Reasonable initial choice, or use after bismuth quadruple therapy fails.

PCAB dual therapy — 1st-line alternative where available

Vonoprazan 20 mg BID + amoxicillin 1 g TID, for 14 days. Recognized by current guidance; not yet established as broadly available in the Canadian market — confirm local availability first.

Clarithromycin triple therapy — restricted use only

PPI BID + clarithromycin 500 mg BID + amoxicillin 1 g BID (or metronidazole 500 mg BID if penicillin-allergic), for 14 days. Do not use empirically — reserve for confirmed clarithromycin susceptibility or documented local resistance under 15%.

Drug / intervention	Role	Dose / use	Important adverse effects	Teaching points
Omeprazole (or equivalent PPI) Preferred	Empiric dyspepsia trial, PUD healing, NSAID gastroprotection	20-40 mg PO daily AC breakfast; empiric trial 4-8 weeks; PUD healing 4-8 weeks (DU) or 8-12 weeks (GU)	Headache, diarrhea, abdominal pain, hypomagnesemia with long-term use	Take 30-60 minutes before the first meal of the day for maximal acid suppression. Any PPI in the class is an equally acceptable choice.
Famotidine Alternative	H2RA option; step-down after PPI; not for active H. pylori-negative PUD healing where a PPI is preferred	20 mg PO BID or 40 mg PO QHS	Headache, diarrhea, confusion (elderly, renal impairment)	Preferred H2RA in Canada — ranitidine has limited/discontinued Canadian availability following NDMA-related recalls.
Bismuth quadruple therapy (PPI + bismuth + tetracycline + metronidazole) Preferred	H. pylori eradication, 1st line	See Drug Tables for full component dosing — 14 days	Diarrhea, black stools/tongue (bismuth), photosensitivity (tetracycline)	Current preferred 1st-line regimen given clarithromycin resistance. Counsel that black stool/tongue from bismuth is expected and harmless.
Rifabutin triple therapy (PPI + amoxicillin + rifabutin) Preferred	H. pylori eradication, 1st-line alternative or after BQT failure	See Drug Tables for full component dosing — 14 days	GI upset; reversible leukopenia/thrombocytopenia with prolonged or repeated courses	Do not exceed rifabutin 150 mg/day for H. pylori treatment — this trial-validated low dose specifically limits myelosuppression risk.
Clarithromycin triple therapy (PPI + clarithromycin + amoxicillin or metronidazole) Special situation	H. pylori eradication only with confirmed susceptibility	See Drug Tables for full component dosing — 14 days	GI upset, taste disturbance	Do not use empirically — reserve for confirmed clarithromycin-susceptible infection or documented local resistance under 15%.
Misoprostol Alternative	NSAID ulcer prevention when PPI is not an option	200 mcg PO QID with food	Diarrhea (dose-related, often limiting), abdominal cramps	Contraindicated in pregnancy (abortifacient) — confirm negative pregnancy status and reliable contraception before starting in a patient who could become pregnant.
Celecoxib Special situation	NSAID substitute lowering GI (but not cardiovascular) risk in high-GI-risk patients	100-200 mg PO BID (osteoarthritis/analgesic dosing)	Same cardiovascular risk as traditional NSAIDs; GI risk lower but not zero	Avoid in established cardiovascular disease. Combine with a PPI, not instead of one, in very-high-GI-risk patients.
Domperidone Alternative	Functional dyspepsia (postprandial distress syndrome) prokinetic option	10 mg PO TID before meals, max 30 mg/day	QTc prolongation, hyperprolactinemia	Obtain a baseline ECG before starting given arrhythmia risk with QTc prolongation.
Amitriptyline (low dose) Alternative	Functional dyspepsia (epigastric pain syndrome), after PPI/H. pylori failure	10-25 mg PO QHS, titrate as tolerated	Drowsiness, dry mouth, constipation	Start low and titrate slowly; counsel on next-day sedation.

Special Populations

Pregnancy: antacids, alginates, H2RAs (famotidine, nizatidine, cimetidine), and PPIs are all generally considered safe options for dyspepsia symptoms in pregnancy.^[7] If H. pylori testing is done during pregnancy (serology, endoscopy, or UBT using the non-radioactive 13C isotope), postpone eradication treatment until after pregnancy and breastfeeding are complete rather than treating during pregnancy. Misoprostol is contraindicated — it is a potent uterine stimulant. NSAIDs after 30 weeks' gestation are associated with premature closure of the fetal ductus arteriosus and oligohydramnios; if an NSAID, ASA, or COX-2 inhibitor is absolutely required, add PPI gastroprotection.

Breastfeeding

PPIs and H2RAs are compatible with breastfeeding at usual doses. Metronidazole (a component of both bismuth quadruple therapy and BV/trichomoniasis regimens) is compatible with breastfeeding; some clinicians advise withholding breastfeeding for 12-24 hours specifically after a single large dose, though this does not apply to the divided daily dosing used in H. pylori regimens.

Pediatrics

Uninvestigated dyspepsia and H. pylori management in children should be directed by a pediatric gastroenterologist rather than managed with the adult algorithm in this chapter — pediatric PPI/H2RA dosing for PUD and H. pylori eradication is weight-based and not established for routine primary-care initiation.

Renal and hepatic impairment

PPIs generally require no dose adjustment in renal impairment. H2RAs (famotidine, nizatidine, cimetidine) require dose reduction in significant renal impairment given increased CNS adverse effect risk (confusion, especially in older adults). Metronidazole and tetracycline require dose adjustment or avoidance in significant hepatic or renal impairment respectively — confirm before starting any H. pylori eradication regimen in a patient with organ impairment.

Older adults

Higher baseline risk of NSAID-related GI complications (age over 65 is itself a risk-stratification criterion) and higher risk of H2RA-related confusion. Long-term PPI use should be reviewed at least annually for ongoing indication given accumulating observational associations with fracture, hypomagnesemia, and enteric infection risk — see Monitoring & Follow-Up.

Monitoring & Follow-Up

Reassess symptom response 4-8 weeks after starting an empiric PPI trial or completing an H. pylori eradication regimen; persistent or recurrent symptoms should prompt the next step in the sequence described in Choose Initial Treatment rather than simply repeating the same therapy. Confirm H. pylori eradication specifically in patients with a history of complicated PUD (bleeding, perforation, obstruction) and in anyone with ongoing or recurrent dyspepsia after treatment — testing (UBT or stool antigen; never serology) should occur at least 4 weeks after finishing antibiotics and bismuth, and at least 1-2 weeks after stopping the PPI (bridge with an H2RA or antacid during this interval if acid suppression is still needed).^[4] Review every patient on long-term PPI therapy at least annually: confirm the original indication still applies, and attempt a trial discontinuation, dose reduction, or step-down to on-demand/H2RA therapy where appropriate — an indefinite PPI prescription without periodic reassessment is not appropriate management.^[8] Recheck hemoglobin/ferritin if iron-deficiency anemia prompted the original workup.

Treatment Failure / Next Step

Confirm adherence to the full prescribed regimen (correct drugs, doses, and duration) before assuming true treatment failure.
For suspected H. pylori eradication failure, confirm with UBT or stool antigen testing (not serology) at the correct interval — do not retreat empirically without confirming persistent infection.
If H. pylori eradication genuinely failed, switch to a different regimen class rather than repeating the same one — for example, move from bismuth quadruple therapy to rifabutin triple therapy, or vice versa.^[4]
After two failed eradication attempts, obtain culture-based susceptibility testing where available, or refer to gastroenterology for tailored salvage therapy.
If PPI empiric therapy for uninvestigated dyspepsia fails and endoscopy has not yet been performed, reconsider whether endoscopy is now warranted, particularly if any alarm feature has since developed.
For functional dyspepsia not responding to the full PPI → TCA → prokinetic sequence, offer psychological therapy and reconsider the diagnosis — a missed motility disorder (gastroparesis) or an alternative cause should be considered in refractory cases.
For NSAID-associated PUD that recurs despite an NSAID being stopped and a PPI given, confirm H. pylori has been tested for and treated, and consider whether the NSAID or ASA source (including OTC use) has truly been eliminated.

Common Errors to Avoid

Using clarithromycin-containing triple therapy as first-line, empiric H. pylori treatment — current resistance rates make this an unreliable choice unless susceptibility is confirmed.
Using serology to confirm H. pylori eradication — it can remain positive for years after successful treatment and will produce a false impression of ongoing infection.
Substituting doxycycline for tetracycline in bismuth quadruple therapy — this measurably lowers eradication rates and should be avoided when tetracycline is obtainable.
Testing for H. pylori eradication too soon — before 4 weeks off antibiotics/bismuth or 1-2 weeks off PPI therapy — which risks a false-negative result.
Requiring endoscopy before starting management in an uninvestigated dyspepsia patient under 60 without alarm features — this delays effective test-and-treat/empiric therapy without added benefit.
Continuing an NSAID indefinitely in a high-GI-risk patient without gastroprotection, or assuming a COX-2 inhibitor alone (without a PPI) is sufficient protection in a very-high-risk patient.
Stopping low-dose ASA prescribed for cardiovascular prophylaxis after a bleeding ulcer instead of continuing it with PPI cover — discontinuation trades a GI risk for a cardiovascular one.
Leaving a patient on long-term PPI therapy indefinitely without an annual reassessment of ongoing indication.
Missing an alarm feature in a patient under 60 because dyspepsia was assumed to be routine and low-risk.

Clinical Decision Algorithm

Uninvestigated dyspepsia (age under 60, no alarm features)

New dyspepsia, age under 60, no alarm features

Non-invasive H. pylori test (UBT or stool antigen preferred)

H. pylori positive

H. pylori eradication therapy (14-day bismuth quadruple therapy 1st line)

H. pylori negative

4-8 week empiric standard-dose PPI trial

Confirm eradication at the correct interval if it was attempted; reassess symptoms after the PPI trial

Symptoms resolve

No further therapy required; step down or discontinue and reassess only if symptoms recur

Symptoms persist

Trial a prokinetic agent or a low-dose tricyclic antidepressant

Age 60+ reached, or any alarm feature develops at any point: refer for upper endoscopy rather than continuing empiric therapy^[2]

Functional dyspepsia (confirmed by endoscopy)

Endoscopy shows no organic pathology — functional dyspepsia confirmed

H. pylori positive

Treat H. pylori (see eradication algorithm)

Symptoms persist despite eradication: proceed as H. pylori-negative

H. pylori negative

Standard-dose PPI trial, 4-8 weeks

PPI (and eradication, if applicable) fails

Low-dose tricyclic antidepressant

TCA fails: prokinetic agent (domperidone or metoclopramide)

All drug therapy fails: psychological therapy (e.g., CBT); reconsider diagnosis, consider selected motility testing if gastroparesis is suspected

H. pylori eradication regimen selection and failure

Confirmed H. pylori infection requiring treatment

1st line: 14-day optimized bismuth quadruple therapy (PPI + bismuth + tetracycline + metronidazole)

Eradication confirmed (UBT/stool antigen, correct interval)

Treatment complete — resume symptom-directed management

Regimen not tolerated or contraindicated

Alternative 1st line: 14-day rifabutin triple therapy (PPI + amoxicillin + rifabutin, max 150 mg/day) or PCAB-amoxicillin dual therapy where available

Eradication fails

Switch regimen class (e.g., bismuth quadruple to rifabutin triple, or vice versa); do not repeat the same failed regimen

Second failure: obtain susceptibility testing where available and refer to gastroenterology for tailored salvage therapy^[4]

NSAID/ASA-associated ulcer prevention and treatment

Patient requires ongoing NSAID or ASA therapy

Assess GI risk: age over 65, high-dose/multiple NSAIDs, concurrent corticosteroid/antiplatelet/anticoagulant/SSRI, severe comorbidity, prior ulcer or GI bleed

Low risk (no risk factors)

NSAID alone; no gastroprotection required

Moderate risk (1-2 risk factors)

NSAID plus once-daily PPI, or switch to a COX-2 inhibitor alone

High risk (multiple risk factors or prior complicated ulcer)

Avoid NSAIDs where possible; if unavoidable, COX-2 inhibitor plus PPI together affords the greatest protection^[9]

Test for and treat H. pylori in every PUD patient, including NSAID/ASA users

Low-dose ASA for cardiovascular prophylaxis: continue ASA with ongoing PPI cover rather than stopping it, even after a bleeding ulcer^[6]

Drug Tables

How to use this table: Doses are adult doses and require patient-specific confirmation, including renal/hepatic adjustment. Select any drug name to open its complete Pharmasist Drug Database page.

Proton pump inhibitors

Any agent in this class is an acceptable choice for empiric dyspepsia trials, PUD healing, and NSAID gastroprotection at standard dose; higher BID dosing applies specifically within H. pylori eradication regimens. Duodenal ulcer healing course is 4-8 weeks; gastric ulcer healing course is 8-12 weeks.

Drug	Dosage	Adverse effects	Comments
Omeprazole	Standard dose: 20-40 mg PO daily AC breakfast H. pylori regimen dose: 20 mg PO BID	Headache, diarrhea, abdominal pain, hypomagnesemia and vitamin B12 reduction with long-term use	Take before the first meal of the day.
Esomeprazole	Standard dose: 20-40 mg PO daily AC breakfast H. pylori regimen dose: 20-40 mg PO BID	Same as omeprazole
Lansoprazole	Standard dose: 15-30 mg PO daily AC breakfast H. pylori regimen dose: 30 mg PO BID	Same as omeprazole
Dexlansoprazole	Standard dose: 30-60 mg PO daily H. pylori regimen dose: 30-60 mg PO BID	Same as omeprazole	Dual-delayed-release formulation, may be taken without regard to meals.
Pantoprazole	Standard dose: 40 mg PO daily AC breakfast H. pylori regimen dose: 40 mg PO BID	Same as omeprazole
Rabeprazole	Standard dose: 20 mg PO daily AC breakfast H. pylori regimen dose: 20 mg PO BID	Same as omeprazole

Histamine H2-receptor antagonists

Alternative to a PPI for symptom control and step-down maintenance; less effective than a PPI for active PUD healing or NSAID gastroprotection. Ranitidine is not included — it has had limited/discontinued Canadian availability since 2019-2020 nitrosamine (NDMA)-related recalls.

Drug	Dosage	Adverse effects	Comments
Famotidine	Treatment: 20 mg PO BID, or 40 mg PO QHS Maintenance: 20 mg PO QHS	Headache, diarrhea, constipation, confusion (elderly, renal impairment)	Preferred H2RA in current Canadian practice.
Nizatidine	Treatment: 150 mg PO BID, or 300 mg PO QHS Maintenance: 150 mg PO QHS	Same as famotidine
Cimetidine	Treatment: 800 mg PO QHS, or 300 mg PO QID, or 600 mg PO BID Maintenance: 400 mg PO QHS, or 300 mg PO BID	Headache, diarrhea, confusion, gynecomastia and impotence (rare)	Clinically significant CYP450 inhibitor (phenytoin, theophylline, warfarin) — famotidine or nizatidine are preferred when a drug interaction risk exists.

Helicobacter pylori eradication — bismuth quadruple therapy (preferred 1st line)

Optimized regimen per the 2024 ACG guideline: bismuth, tetracycline, and metronidazole each at full labeled frequency, for a full 14 days — shortening duration or substituting doxycycline for tetracycline measurably reduces eradication rates.

Drug	Dosage	Adverse effects	Comments
Bismuth subcitrate potassium / metronidazole / tetracycline (co-packaged)	Combo (adults): bismuth subcitrate potassium 140 mg + metronidazole 125 mg + tetracycline 125 mg — 3 capsules QID Plus: PPI standard dose PO BID	Diarrhea, dark/black stool and tongue (expected, harmless), metallic taste, photosensitivity	Canadian product labeling is 3 capsules QID for 10 days with a twice-daily PPI; current guideline evidence supports extending to 14 days for optimal eradication — confirm local practice. Swallow whole with a full glass of water; take with meals and at bedtime.
Individually-dosed bismuth quadruple therapy (when the co-packaged product is unavailable)	PPI: Standard dose PO BID Bismuth subsalicylate: Greater than 300 mg PO QID Tetracycline: 500 mg PO QID Metronidazole: 500 mg PO TID-QID (total greater than 1.5 g/day)	Same as above	Assemble from individual bismuth subsalicylate (over 300 mg per dose), metronidazole, and tetracycline components rather than the co-packaged product; less commonly used in Canadian practice than the branded combination.

Helicobacter pylori eradication — rifabutin triple therapy

Reasonable 1st-line alternative, or salvage therapy after bismuth quadruple therapy failure. Rifabutin resistance in H. pylori is currently rare.

Drug	Dosage	Adverse effects	Comments
Rifabutin	Combo (adults): rifabutin 150 mg once daily + amoxicillin 1 g PO TID + PPI standard dose PO BID — 14 days	GI upset; reversible leukopenia/thrombocytopenia with prolonged or repeated courses; orange discolouration of body fluids	Do not exceed 150 mg/day for H. pylori treatment — this low, trial-validated dose specifically minimizes myelosuppression risk seen with the higher doses used for tuberculosis/MAC treatment. A co-packaged rifabutin/amoxicillin/omeprazole product is not marketed in Canada — prescribe each component separately.

Helicobacter pylori eradication — clarithromycin triple therapy (restricted use)

Do not use empirically. Reserve for confirmed clarithromycin-susceptible infection, or documented and monitored local resistance under 15%.

Drug	Dosage	Adverse effects	Comments
Clarithromycin	Combo (adults): PPI standard dose PO BID + clarithromycin 500 mg PO BID + amoxicillin 1 g PO BID (or metronidazole 500 mg PO BID if penicillin-allergic) — 14 days	GI upset, taste disturbance, QTc prolongation	Numerous CYP3A4 drug interactions — review the full medication list before prescribing.

Helicobacter pylori eradication — salvage/component agents

Used within a quadruple or rescue regimen once first-line therapy has failed and reinfection/nonadherence have been excluded.

Drug	Dosage	Adverse effects	Comments
Amoxicillin	Typical component dose: 1 g PO BID-TID depending on regimen	GI upset, rash, hypersensitivity	Confirm no penicillin allergy before use in any regimen.
Metronidazole	Typical component dose: 500 mg PO TID-QID depending on regimen	GI upset, metallic taste, peripheral neuropathy (prolonged use)	Avoid alcohol during treatment and for the product-specific interval afterward — disulfiram-like reaction.
Tetracycline	Typical component dose: 500 mg PO QID	Photosensitivity, esophageal irritation if taken lying down, tooth discolouration in children	Contraindicated in pregnancy and in children under 8 years. Take with a full glass of water, remain upright afterward.
Levofloxacin	Salvage regimen component: 500 mg PO once daily, combined with a PPI and amoxicillin	Tendinopathy/tendon rupture, QTc prolongation, peripheral neuropathy, CNS effects	Second-line/salvage option only, given rising levofloxacin resistance; use only when first-line options have failed or are contraindicated.

Potassium-competitive acid blocker (PCAB) dual therapy

Vonoprazan-amoxicillin dual therapy is recognized as a reasonable 1st-line alternative by the 2024 ACG guideline internationally; as of this writing vonoprazan is not established as broadly available in the Canadian market — confirm local availability before selecting this option.

Drug	Dosage	Adverse effects	Comments
Vonoprazan + amoxicillin	Reported regimen (where available): Vonoprazan 20 mg PO BID + amoxicillin 1 g PO TID, 14 days	GI upset; class effects similar to PPIs	Not currently linked to a Canadian Drug Database monograph pending confirmed local availability.

Mucosal protective / prokinetic / neuromodulator agents

Used for NSAID ulcer prevention (misoprostol, sucralfate) or functional dyspepsia (prokinetics, neuromodulators) rather than for H. pylori eradication.

Drug	Dosage	Adverse effects	Comments
Misoprostol	NSAID ulcer prevention: 200 mcg PO QID with food	Diarrhea (dose-related), abdominal cramps, flatulence	Contraindicated in pregnancy (abortifacient). An accepted gastroprotective alternative to a PPI, though generally less well tolerated.
Sucralfate	PUD healing (adjunct/alternative): 1 g PO QID on an empty stomach	Constipation; may impair absorption of other oral drugs given concurrently	Give other oral medications at least 2 hours apart from sucralfate given its drug-binding potential.
Domperidone	Functional dyspepsia (PDS): 10 mg PO TID before meals, max 30 mg/day	QTc prolongation, hyperprolactinemia	Baseline ECG recommended before starting.
Metoclopramide	Functional dyspepsia (PDS): 5-10 mg PO TID-QID before meals	Drowsiness, extrapyramidal symptoms, tardive dyskinesia with prolonged use	Discontinue immediately at first sign of dystonia, tremor, or muscle stiffness; limit duration of use.
Amitriptyline	Functional dyspepsia (EPS): 10-25 mg PO QHS, titrate as tolerated	Drowsiness, dry mouth, constipation, QTc prolongation at higher doses	Low-dose neuromodulator use for functional dyspepsia (EPS), distinct from antidepressant dosing.
Buspirone	Functional dyspepsia: 10 mg PO TID	Dizziness, headache, nausea	An alternative neuromodulator option, notably a fundus-relaxing agent that may particularly help postprandial fullness.
Mirtazapine	Functional dyspepsia: 15 mg PO QHS	Somnolence, increased appetite/weight gain	May be particularly useful in functional dyspepsia patients with concurrent weight loss or poor appetite.

NSAID-sparing / gastroprotective options

For patients requiring ongoing anti-inflammatory therapy who are at moderate-to-high GI risk.

Drug	Dosage	Adverse effects	Comments
Celecoxib	Typical dose: 100-200 mg PO BID, indication-dependent	Same cardiovascular risk as traditional NSAIDs; lower (not zero) GI risk	The only COX-2 inhibitor available in Canada. Avoid in established cardiovascular disease. Combine with a PPI rather than relying on COX-2 selectivity alone in very-high-risk patients.

Evidence note: Rifabutin triple-therapy dosing (rifabutin capped at 150 mg/day) reflects the pivotal RHB-105 trial design, which deliberately used this low dose to minimize myelosuppression risk relative to the higher, longer-course rifabutin regimens used for tuberculosis or Mycobacterium avium complex.^[10] NSAID/ASA gastrointestinal risk stratification (low/moderate/high risk categories and the corresponding gastroprotection strategy) follows the ACCF/ACG/AHA expert consensus framework.^[11]

References

Gastroduodenal disorders (Rome IV) — Gastroenterology (Stanghellini V, Chan FKL, Hasler WL, et al.). Gastroenterology 2016;150(6):1380-1392
ACG and CAG Clinical Guideline: Management of Dyspepsia — American Journal of Gastroenterology, American College of Gastroenterology / Canadian Association of Gastroenterology (Moayyedi PM, Lacy BE, Andrews CN, Enns RA, Howden CW, Vakil N). Am J Gastroenterol 2017;112(7):988-1013
Non-invasive diagnostic tests for Helicobacter pylori infection — Cochrane Database of Systematic Reviews (Best LM, Takwoingi Y, Siddique S, et al.). Cochrane Database Syst Rev 2018;3(3):CD012080
ACG Clinical Guideline: Treatment of Helicobacter pylori Infection — American Journal of Gastroenterology, American College of Gastroenterology (Chey WD, Howden CW, Moss SF, Morgan DR, Greer KB, Grover S, Shah SC). Am J Gastroenterol 2024;119(9):1730-1753
Guidelines for Prevention of NSAID-Related Ulcer Complications — American Journal of Gastroenterology, American College of Gastroenterology (Lanza FL, Chan FK, Quigley EM). Am J Gastroenterol 2009;104(3):728-738
Continuation of low-dose aspirin therapy in peptic ulcer bleeding: a randomized trial — Annals of Internal Medicine (Sung JJ, Lau JY, Ching JY, et al.). Ann Intern Med 2010;152(1):1-9
The safety of proton pump inhibitors (PPIs) in pregnancy: a meta-analysis — American Journal of Gastroenterology (Gill SK, O'Brien L, Einarson TR, Koren G). Am J Gastroenterol 2009;104(6):1541-1545
Appropriate prescribing and deprescribing of proton pump inhibitors: New Choosing Wisely Canada toolkit — Canadian Family Physician (Bland E, Veldhuyzen van Zanten S, Thompson W). Can Fam Physician 2026;72(3):179-183
Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibitor for prevention of recurrent ulcer bleeding in patients at very high risk: a double-blind, randomised trial — Lancet (Chan FK, Wong VW, Suen BY, et al.). Lancet 2007;369(9573):1621-1626
Rifabutin-Based Triple Therapy (RHB-105) for Helicobacter pylori Eradication: A Double-Blind, Randomized, Controlled Trial — Annals of Internal Medicine (Graham DY, Canaan Y, Maher J, Wiener G, Hulten KG, Kalfus IN). Ann Intern Med 2020;172(12):795-802
ACCF/ACG/AHA 2008 Expert Consensus Document on Reducing the Gastrointestinal Risks of Antiplatelet Therapy and NSAID Use — Circulation, American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents (Bhatt DL, Scheiman J, Abraham NS, et al.). Circulation 2008;118(18):1894-1909
Status of ranitidine drugs in Canada — Health Canada Recalls and Safety Alerts Database. Health Canada recall advisory

Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.