Peptic ulceration
Peptic ulceration commonly involves the stomach, duodenum, and lower oesophagus; after gastric surgery it involves the gastro-enterostomy stoma. Healing can be promoted by general measures, stopping smoking and taking antacids and by antisecretory drug treatment, but relapse is common when treatment ceases. Nearly all duodenal ulcers and most gastric ulcers not associated with NSAIDs are caused byHelicobacter pylori.
Helicobacter pylori infection
Eradication ofHelicobacter pylorireduces recurrence of gastric and duodenal ulcers and the risk of rebleeding. It also causes regression of most localised gastric mucosa associated lymphoid-tissue (MALT) lymphomas. The presence ofH. pylorishould be confirmed before starting eradication treatment. Acid inhibition combined with antibacterial treatment is highly effective in the eradication ofH. pylori; reinfection is rare. Antibiotic associated colitis is an uncommon risk.
For initial treatment, a one-week triple-therapy regimen that comprises a proton pump inhibitor, clarithromycin p.470, andeitheramoxicillin p.482ormetronidazole p.475can be used. However, if a patient has been treated with metronidazole for other infections, a regimen containing a proton pump inhibitor, amoxicillin and clarithromycin is preferred for initial therapy. If a patient has been treated with a macrolide for other infections, a regimen containing a proton pump inhibitor, amoxicillin and metronidazole is preferred for initial therapy. These regimens eradicateH. pyloriin about85% of cases. There is usually no need to continue antisecretory treatment (with a proton pump inhibitor or H2-receptor antagonist), however, if the ulcer is large, or complicated by haemorrhage or perforation, then antisecretory treatment is continued for a further3weeks. Treatment failure usually indicates antibacterial resistance or poor compliance. Resistance to amoxicillin is rare. However, resistance to clarithromycin and metronidazole is common and can develop during treatment.
Two-week triple-therapy regimens offer the possibility of higher eradication rates compared to one-week regimens, but adverse effects are common and poor compliance is likely to offset any possible gain.
Two-week dual-therapy regimens using a proton pump inhibitor and a single antibacterial are licensed, but produce low rates ofH. pylorieradication and arenotrecommended.
Tinidazole p.476is also used occasionally forH. pylori eradication as an alternative to metronidazole; tinidazole should be combined with antisecretory drugs and other antibacterials.
Routine retesting, to confirm eradication, is not necessary unless the patient has gastric MALT lymphoma or complicatedH. pyloriassociated peptic ulcer.
A two-week regimen comprising a proton pump inhibitor plustripotassium dicitratobismuthate p.63,plus tetracycline p.498,plusmetronidazole can be used for eradication failure. Alternatively, the patient can be referred for endoscopy and treatment based on the results of culture and sensitivity testing.
See underNSAID-associated ulcersfor the role ofH. pylori eradication therapy in patients starting or taking a NSAID.
Also see Dyspepsia p.57forH. pylorieradication in patients with dyspepsia.
BNF70 Gastric and duodenal ulceration 61
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Test forHelicobacter pylori
13C-Urea breath test kits are available for the diagnosis of gastro-duodenal infection withHelicobacter pylori. The test involves collection of breath samples before and after ingestion of an oral solution of13C-urea; the samples are sent for analysis by an appropriate laboratory. The test should not be performed within4weeks of treatment with an antibacterial or within2weeks of treatment with an antisecretory drug. A specific13Curea breath test kit for children is available (Helicobacter Test INFAI for children of the age3–11®). However, the appropriateness of testing for H. pyloriinfection in children has not been established.
NSAID-associated ulcers
Gastro-intestinal bleeding and ulceration can occur with NSAID use. The risk of serious upper gastro-intestinal side- effects varies between individual NSAIDs. Whenever possible, the NSAID should bewithdrawnif an ulcer occurs.
Patients at high risk of developing gastro-intestinal complications with a NSAID include those aged over65 years, those with a history of peptic ulcer disease or serious gastro-intestinal complication, those taking other medicines that increase the risk of gastro-intestinal side- effects, or those with serious co-morbidity (e.g.
cardiovascular disease, diabetes, renal or hepatic impairment). In those at risk of ulceration, a proton pump inhibitor can be considered for protection against gastric and duodenal ulcers associated with non-selective NSAIDs;
a H2-receptor antagonist such as ranitidine p.65given at twice the usual dose or misoprostol p.710are alternatives.
Colic and diarrhoea may limit the dose of misoprostol. Its use is most appropriate for the frail or very elderly from whom NSAIDs cannot be withdrawn. A combination of a cyclo-oxygenase-2selective inhibitor with a proton pump inhibitor may be more appropriate for those with a history of upper gastro-intestinal bleeding or3or more risk factors for gastro-intestinal ulceration, but see NSAIDs and Cardiovascular Events.
NSAID use andH. pyloriinfection are independent risk factors for gastro-intestinal bleeding and ulceration. In patients already taking a NSAID, eradication ofH. pyloriis unlikely to reduce the risk of NSAID-induced bleeding or ulceration. However, in patients with dyspepsia or a history of gastric or duodenal ulcer, who areH. pyloripositive, and who are about to start long-term treatment with a non- selective NSAID, eradication ofH. pylorimay reduce the overall risk of ulceration.
In a patient who has developed an ulcer, if theNSAID can be discontinued, a proton pump inhibitor usually produces the most rapid healing; alternatively, the ulcer can be treated with a H2-receptor antagonist or misoprostol p.710. On healing, patients should be tested forH. pyloriand given
eradication therapy ifH. pyloriis present (see also Test for Helicobacter pylori).
Iftreatment with a non-selective NSAID needs to continue, the following options are suitable:
.Treat ulcer with a proton pump inhibitor and on healing continue the proton pump inhibitor (dose not normally reduced because asymptomatic ulcer recurrence may occur);
.Treat ulcer with a proton pump inhibitor and on healing switch to misoprostol for maintenance therapy (colic and diarrhoea may limit the dose of misoprostol);
.Treat ulcer with a proton pump inhibitor and switch non-selective NSAID to a cyclo-oxygenase-2selective inhibitor, but see NSAIDs and Cardiovascular Events;
on healing, continuation of the proton pump inhibitor in patients with a history of upper gastro-intestinal bleeding may provide further protection against recurrence.
Iftreatment with a cyclo-oxygenase-2selective inhibitor needs to continue,treat ulcer with a proton pump inhibitor;
on healing continuation of the proton pump inhibitor in patients with a history of upper gastro-intestinal bleeding may provide further protection against recurrence.
GASTROPROTECTIVE COMPLEXES AND CHELATORS
Chelates and complexes
Tripotassium dicitratobismuthate p.63is a bismuth chelate effective in healing gastric and duodenal ulcers. See under Peptic ulceration p.61for the role of tripotassium dicitratobismuthate p.63in aHelicobacter pylorieradication regimen for those who have not responded to first-line regimens.
The bismuth content of tripotassium dicitratobismuthate p.63is low but absorption has been reported;
encephalopathy (described with older high-dose bismuth preparations) has not been reported.
Sucralfate p.63may act by protecting the mucosa from acid-pepsin attack in gastric and duodenal ulcers. It is a complex of aluminium hydroxide and sulfated sucrose but has minimal antacid properties.
Recommended regimens for Helicobacter pylori eradication
Acid suppressant Antibacterial
Price for7-day course Amoxicillin Clarithromycin Metronidazole
Esomeprazole20mg
twice daily 1g twice daily
— 500mg twice daily
250mg twice daily —
400mg twice daily
£6.63
£4.30 Lansoprazole30mg
twice daily 1g twice daily
1g twice daily
—
500mg twice daily 250mg twice daily—
400mg twice daily— 400mg twice daily
£5.52
£3.70
£3.19 Omeprazole20mg twice
daily 1g twice daily
500mg3times a day
—
500mg twice daily 250mg twice daily—
400mg3—times a day 400mg twice daily
£5.36
£3.40
£3.03 Pantoprazole40mg
twice daily
1g twice daily
— 500mg twice daily
250mg twice daily
400mg twice daily—
£5.48
£3.15 Rabeprazole sodium
20mg twice daily
1g twice daily
— 500mg twice daily
250mg twice daily
400mg twice daily—
£6.04
£3.71
62 Disorders of gastric acid and ulceration BNF70
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Sucralfate
INDICATIONS AND DOSE
Benign gastric ulceration|Benign duodenal ulceration BY MOUTH
▶Child 15–17 years:2g twice daily, dose to be taken on rising and at bedtime, alternatively1g4times a day for4–6weeks, or in resistant cases up to12weeks, dose to be taken1hour before meals and at bedtime;
maximum8g per day
▶Adult:2g twice daily, dose to be taken on rising and at bedtime, alternatively1g4times a day for4–6weeks, or in resistant cases up to12weeks, dose to be taken1 hour before meals and at bedtime; maximum8g per day
Chronic gastritis BY MOUTH
▶Child 15–17 years:2g twice daily, dose to be taken on rising and at bedtime, alternatively1g4times a day for4–6weeks or in resistant cases up to12weeks, dose to be taken1hour before meals and at bedtime;
maximum8g per day
▶Adult:2g twice daily, dose to be taken on rising and at bedtime, alternatively1g4times a day for4–6weeks or in resistant cases up to12weeks, dose to be taken1 hour before meals and at bedtime; maximum8g per day
Prophylaxis of stress ulceration in child under intensive care
BY MOUTH
▶Child 15–17 years:1g6times a day; maximum8g per day
Prophylaxis of stress ulceration BY MOUTH
▶Adult:1g6times a day; maximum8g per day
lUNLICENSED USE
▶In childrenNot licensed for use in children under15years.
Tablets not licensed for prophylaxis of stress ulceration.
lCAUTIONSPatients under intensive care (Important:
reports of bezoar formation) CAUTIONS, FURTHER INFORMATION
Bezoar formationFollowing reports of bezoar formation associated with sucralfate, caution is advised in seriously ill patients, especially those receiving concomitant enteral feeds or those with predisposing conditions such as delayed gastric emptying.
lINTERACTIONS→Appendix1(sucralfate).
lSIDE-EFFECTS
▶Common or very commonConstipation
▶UncommonBack pain.bezoar formation.diarrhoea.
dizziness.drowsiness.dry mouth.eadache.flatulence.
gastric discomfort.indigestion.nausea.rash
lPREGNANCYNo evidence of harm; absorption from gastro-intestinal tract negligible.
lBREAST FEEDINGAmount probably too small to be harmful.
lRENAL IMPAIRMENTUse with caution; aluminium is absorbed and may accumulate.
lDIRECTIONS FOR ADMINISTRATION Administration of sucralfate and enteral feeds should be separated by1hour and for administration bymouth, sucralfate should be given1hour before meals.Oral suspensionblocks fine- bore feeding tubes. Crushedtabletsmay be dispersed in water.
lPRESCRIBING AND DISPENSING INFORMATIONFlavours of oral liquid formulations may include aniseed and caramel.
lMEDICINAL FORMS
There can be variation in the licensing of different medicines containing the same drug. Forms available from special-order manufacturers include: oral suspension, cream, powder, enema
Tablet
CAUTIONARY AND ADVISORY LABELS5
▶Antepsin(Chugai Pharma UK Ltd)
Sucralfate 1 gramAntepsin1g tablets|50tabletP£6.36DT price = £6.36
Oral suspension
CAUTIONARY AND ADVISORY LABELS5
▶Antepsin(Chugai Pharma UK Ltd)
Sucralfate 200 mg per 1 mlAntepsin1g/5ml oral suspension (sugar-free)|250mlP£6.36DT price = £6.36
Tripotassium dicitratobismuthate
INDICATIONS AND DOSE
Eradication failure ofHelicobacter pylori infection (in combination with omeprazole, tetracycline and metronidazole)
BY MOUTH
▶Adult:120mg4times a day for2weeks Benign gastric and duodenal ulceration BY MOUTH
▶Adult:240mg twice daily, alternatively120mg4times a day both dosage regimens taken for28days followed by a further28days if necessary, maintenance dose not indicated but course may be repeated after interval of1month
lINTERACTIONS→Appendix1(tripotassium dicitratobismuthate).
lSIDE-EFFECTS
▶Common or very commonMay blacken faeces.may darken tongue
▶UncommonConstipation.diarrhoea.nausea.pruritus.
rash.vomiting
lPREGNANCYManufacturer advises avoid on theoretical grounds.
lBREAST FEEDINGNo information available.
lRENAL IMPAIRMENTAvoid in severe impairment.
lDIRECTIONS FOR ADMINISTRATIONTo be swallowed with half a glass of water. Twice-daily dosage to be taken30 minutes before breakfast and main evening meal. Four- times-daily dosage to be taken as follows: one dose30 minutes before breakfast, midday meal and main evening meal, and one dose2hours after main evening meal.
lPATIENT AND CARER ADVICEMilk should not be drunk by itself during treatment but small quantities may be taken in tea or coffee or on cereal. Antacids, fruit, or fruit juice should not be taken half an hour before or after a dose.
Patients and carers should be aware that the patient may develop darkened tongue and blackened faeces.
lMEDICINAL FORMS
There can be variation in the licensing of different medicines containing the same drug.
Tablet
ELECTROLYTES:May contain Potassium
▶De-Noltab(Astellas Pharma Ltd)
Tripotassium dicitratobismuthate 120 mgDe-Noltab120mg tablets|112tabletp£5.09
BNF70 Gastric and duodenal ulceration 63
Gastro-intestinalsystem
1
H2-RECEPTOR ANTAGONISTS
H2-receptor antagonists
Histamine H2-receptor antagonistshealgastric and duodenal ulcersby reducing gastric acid output as a result of histamine H2-receptor blockade; they are also used to relieve symptoms ofgastro-oesophageal reflux disease. H2- receptor antagonists should not normally be used for Zollinger-Ellison syndromebecause proton pump inhibitors are more effective.
Maintenance treatment with low doses for the prevention of peptic ulcer disease has largely been replaced in Helicobacter pyloripositive patients by eradication regimens.
In adults, H2-receptor antagonists are used for the treatment offunctional dyspepsiaand may be used for the treatment ofuninvestigated dyspepsiawithout alarm features.
H2-receptor antagonist therapy can promote healing of NSAID-associated ulcers (particularly duodenal).
Treatment with a H2-receptor antagonist has not been shown to be beneficial in haematemesis and melaena, but prophylactic use reduces the frequency of bleeding from gastroduodenal erosions in hepatic coma, and possibly in other conditions requiring intensive care. H2- receptor antagonists also reduce the risk ofacid aspirationin obstetric patients at delivery (Mendelson’s syndrome).
H2-receptor antagonists f lCAUTIONSSigns and symptoms of gastric cancer
CAUTIONS, FURTHER INFORMATION
Gastric cancerH2-receptor antagonists might mask symptoms of gastric cancer; particular care is required in patients presenting with‘alarm features’in such cases gastric malignancy should be ruled out before treatment.
lSIDE-EFFECTS
▶Common or very commonDiarrhoea.dizziness.headache
▶UncommonErythema multiforme.rash.toxic epidermal necrolysis
▶RareArthralgia.blood disorders.bradycardia.
cholestatic jaundice.confusion.depression.
hallucinations.hepatitis.leucopenia.myalgia.
pancytopenia.psychiatric reactions.thrombocytopenia
▶Frequency not knownGynaecomastia.impotence SIDE-EFFECTS, FURTHER INFORMATION
Psychiatric reactionsPsychiatric reactions, including confusion, depression, and hallucinations occur particularly in the elderly or the very ill.
Cimetidine F
INDICATIONS AND DOSE Benign duodenal ulceration BY MOUTH
▶Adult:400mg twice daily for at least4weeks, to be taken with breakfast and at night, alternatively800mg once daily for at least4weeks, to be taken at night;
increased if necessary up to400mg4times a day;
maintenance400mg once daily, to be taken at night, alternatively maintenance400mg twice daily, to be taken in the morning and at night
Benign gastric ulceration BY MOUTH
▶Adult:400mg twice daily for6weeks, to be taken with breakfast and at night, alternatively800mg daily for6 weeks, to be taken at night; increased if necessary up
to400mg4times a day; maintenance400mg once daily, to be taken at night, alternatively maintenance 400mg twice daily, to be taken in the morning and at night
NSAID-associated ulceration BY MOUTH
▶Adult:400mg twice daily for8weeks, to be taken with breakfast and at night, alternatively800mg daily for8 weeks, to be taken at night; increased if necessary up to400mg4times a day; maintenance400mg daily, to be taken at night, alternatively maintenance400mg twice daily, to be taken in the morning and at night Reflux oesophagitis
BY MOUTH
▶Adult:400mg4times a day for4–8weeks Prophylaxis of stress ulceration
BY MOUTH
▶Adult:200–400mg every4–6hours Gastric acid reduction in obstetrics BY MOUTH
▶Adult:Initially400mg, to be administered at start of labour, then increased if necessary up to400mg every 4hours, do not use syrup in prophylaxis of acid aspiration; maximum2.4g per day
Gastric acid reduction during surgical procedures BY MOUTH
▶Adult:400mg, to be given90–120minutes before induction of general anaesthesia
Short-bowel syndrome BY MOUTH
▶Adult:400mg twice daily, adjusted according to response, to be taken with breakfast and at bedtime To reduce degradation of pancreatic enzyme supplements BY MOUTH
▶Adult:0.8–1.6g daily in4divided doses, dose to be taken1–1ẵ hours before meals
lINTERACTIONS→Appendix1(histamine H2-antagonists).
lSIDE-EFFECTS
▶Common or very commonMalaise
▶UncommonTachycardia
▶RareInterstitial nephritis
▶Very rarealopecia.galactorrhoea.pancreatitis.vasculitis
lPREGNANCYManufacturer advises avoid unless essential.
lBREAST FEEDINGSignificant amount present in milk—not known to be harmful but manufacturer advises avoid.
lHEPATIC IMPAIRMENTReduce dose. Increased risk of confusion.
lRENAL IMPAIRMENTOccasional risk of confusion.
Reduce dose to200mg4times daily if eGFR
30–50mL/minute/1.73m2. Reduce dose to200mg3times daily if eGFR15–30mL/minute/1.73m2. Reduce dose to 200mg twice daily if eGFR less than
15mL/minute/1.73m2.
lEXCEPTIONS TO LEGAL CATEGORYCimetidine can be sold to the public for adults and children over16years (provided packs do not contain more than2weeks’ supply) for the short-term symptomatic relief of heartburn, dyspepsia, and hyperacidity (max. single dose 200mg, max. daily dose800mg), and for the prophylactic management of nocturnal heartburn (single night-time dose100mg).
lMEDICINAL FORMS
There can be variation in the licensing of different medicines containing the same drug.
Tablet
▶CIMETIDINE (Non-proprietary)
Cimetidine 200 mgCimetidine200mg tablets|60tabletP
£40.00DT price = £5.04
64 Disorders of gastric acid and ulceration BNF70
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Cimetidine 400 mgCimetidine400mg tablets|60tabletP
£40.00DT price = £1.76
Cimetidine 800 mgCimetidine800mg tablets|30tabletP
£48.00DT price = £9.30
▶Tagamet(Chemidex Pharma Ltd)
Cimetidine 200 mgTagamet200mg tablets|120tabletP
£19.58
Cimetidine 400 mgTagamet400mg tablets|60tabletP
£22.62DT price = £1.76
Cimetidine 800 mgTagamet800mg tablets|30tabletP
£22.62DT price = £9.30 Oral solution
EXCIPIENTS:May contain Propylene glycol
▶CIMETIDINE (Non-proprietary)
Cimetidine 40 mg per 1 mlCimetidine200mg/5ml oral solution sugar free (sugar-free)|300mlP£14.24–£14.25DT price =
£14.25
▶Tagamet(Chemidex Pharma Ltd)
Cimetidine 40 mg per 1 mlTagamet200mg/5ml syrup| 600mlP£28.49DT price = £28.49
Famotidine F
INDICATIONS AND DOSE
Treatment of benign gastric and duodenal ulceration BY MOUTH
▶Adult:40mg once daily for4–8weeks, dose to be taken at night
Maintenance treatment of duodenal ulceration BY MOUTH
▶Adult:20mg once daily, dose to be taken at night Reflux oesophagitis
BY MOUTH
▶Adult:20–40mg twice daily for6–12weeks;
maintenance20mg twice daily
lINTERACTIONS→Appendix1(histamine H2-antagonists).
lSIDE-EFFECTS
▶Common or very commonConstipation
▶Uncommonfatigue.vomiting.anorexia.dry mouth.
flatulence.nausea.taste disorders
▶Very rareChest tightness.interstitial pneumonia.
paraesthesia.seizures
lPREGNANCYManufacturer advises avoid unless potential benefit outweighs risk.
lBREAST FEEDINGPresent in milk—not known to be harmful but manufacturer advises avoid.
lRENAL IMPAIRMENTUse normal dose every36–48hours or use half normal dose if eGFR less than
50mL/minute/1.73m2. Seizures reported very rarely.
lEXCEPTIONS TO LEGAL CATEGORYFamotidine can be sold to the public for adults and children over16years (provided packs do not contain more than2weeks’ supply) for the short-term symptomatic relief of heartburn, dyspepsia, and hyperacidity, and for the prevention of these symptoms when associated with consumption of food or drink including when they cause sleep disturbance (max. single dose10mg, max. daily dose20mg).
lMEDICINAL FORMS
There can be variation in the licensing of different medicines containing the same drug.
Tablet
▶FAMOTIDINE (Non-proprietary)
Famotidine 20 mgFamotidine20mg tablets|28tabletP
£22.00DT price = £17.58
Famotidine 40 mgFamotidine40mg tablets|28tabletP
£39.00DT price = £38.72
Nizatidine F
INDICATIONS AND DOSE
Benign gastric, duodenal or NSAID-associated ulceration BY MOUTH
▶Adult:300mg once daily for4–8weeks, dose to be taken in the evening, alternatively150mg twice daily for4–8weeks; maintenance150mg once daily, dose to be taken at night
Gastro-oesophageal reflux disease BY MOUTH
▶Adult:150–300mg twice daily for up to12weeks
lINTERACTIONS→Appendix1(histamine H2-antagonists).
lSIDE-EFFECTS
▶Common or very commonSweating
▶RareFever.hyperuricaemia.nausea.vasculitis
lPREGNANCYManufacturer advises avoid unless essential.
lBREAST FEEDINGAmount too small to be harmful.
lHEPATIC IMPAIRMENTManufacturer advises caution.
lRENAL IMPAIRMENTUse half normal dose if eGFR 20–50mL/minute/1.73m2. Use one-quarter normal dose if eGFR less than20mL/minute/1.73m2.
lEXCEPTIONS TO LEGAL CATEGORYNizatidine can be sold to the public for the prevention and treatment of symptoms of food-related heartburn and meal-induced indigestion in adults and children over16years; max.
single dose75mg, max. daily dose150mg for max.14 days.
lMEDICINAL FORMS
There can be variation in the licensing of different medicines containing the same drug. Forms available from special-order manufacturers include: oral solution, oral suspension Capsule
▶NIZATIDINE (Non-proprietary)
Nizatidine 150 mgNizatidine150mg capsules|30capsuleP
£12.20DT price = £5.40
Nizatidine 300 mgNizatidine300mg capsules|30capsuleP
£17.40DT price = £15.43
Ranitidine F
INDICATIONS AND DOSE
Benign gastric ulceration|Duodenal ulceration BY MOUTH
▶Child 1–5 months:1mg/kg3times a day (max. per dose 3mg/kg3times a day)
▶Child 6 months–2 years:2–4mg/kg twice daily
▶Child 3–11 years:2–4mg/kg twice daily (max. per dose 150mg) for4–8weeks
▶Child 12–17 years:150mg twice daily for4–8weeks, alternatively300mg once daily for4–8weeks, dose to be taken at night
▶Adult:150mg twice daily for4–8weeks, alternatively 300mg once daily for4–8weeks, dose to be taken at night
Chronic episodic dyspesia BY MOUTH
▶Child 12–17 years:150mg twice daily for6weeks, alternatively300mg once daily for6weeks, dose to be taken at night
▶Adult:150mg twice daily for6weeks, alternatively 300mg once daily for6weeks, dose to be taken at
night continued→
BNF70 Gastric and duodenal ulceration 65
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