NPS Prescribing Practice Review 34: Proton pump inhibitors in primary care
Published in MedicineWise News
Date published: About this date
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- Prescribe a 4-week course when initiating a proton pump inhibitor (PPI)
- Step down to intermittent, symptom-driven PPI therapy or to a lower dose if maintenance is required
- Communicate the goal and duration of PPI therapy to the patient and on referral or hospital discharge
- Review the underlying need for an NSAID before considering co-prescribing a PPI
PPIs are now the standard treatment for gastro-oesophageal reflux disease (GORD)
Proton pump inhibitors (PPIs) provide rapid and effective control of the symptoms of gastro-oesophageal reflux disease (GORD) and dyspepsia, with few adverse effects. These are now prescribed in most new cases of GORD.A Continuous use at a standard dose is common practice, but may represent more intensive therapy than many patients require.A. Source: BEACH data, Australian General Practice Statistics and Classification Centre, a collaborating unit of the Family Medicine Research Centre, University of Sydney and the Australian Institute of Health and Welfare.
Initiating treatment with a proton pump inhibitor
Are there alarm symptoms?
Refer patients with one or more alarm symptoms (gastrointestinal bleeding, upper abdominal mass, difficulty/pain on swallowing, unexplained weight loss or persistent vomiting) for endoscopy — on the same day in cases of significant acute bleeding.1,2
In the absence of alarm symptoms, empirical PPI therapy is suitable for patients with dyspeptic symptoms.1,2
Prescribe a single 4-week course in uninvestigated dyspepsia or newly diagnosed GORD
A single initial course of standard-dose PPI (see Table 1) will control symptoms and heal gastro-oesophageal lesions3; oesophagitis healing rates average about 75% after 4 weeks of therapy.3 Patients with persistent or recurring symptoms should return for review.
More than 1 patient in 5 has at most mild symptoms for at least the next 6 months after a short course of a PPI.3–5 If symptoms do require ongoing management, step down to low-dose or intermittent, symptom-driven therapy (see How to step down PPI therapy). Continuous standard-dose maintenance therapy is indicated if severe or complicated oesophagitis has been established by endoscopy.
Consider test-and-treat for Helicobacter pylori infection in uninvestigated dyspepsia without predominant GORD symptoms
Patients with predominant symptoms of heartburn or acid regurgitation are likely to have GORD and should be treated as above. For others, testing for H. pylori infection and treating with triple therapy is an alternative to empirical PPI treatment. This controls symptoms for 12 months in about 60% of those testing positive for H. pylori.3
Review maintenance therapy once or twice yearly
In patients taking maintenance PPIs, review to determine ongoing need. Step down to intermittent or low-dose therapy if symptoms are well controlled, or discuss stopping therapy (unless there is a diagnosis of severe oesophagitis, strictures, scleroderma or Barrett's oesophagus).1,2
A small proportion of patients with an inadequate response to standard-dose PPI may require a high-dose PPI or referral to a specialist.
Discuss intermittent, symptom-driven maintenance therapy
Evidence from randomised controlled trials in non-erosive and mild erosive GORD shows that intermittent, symptom-driven maintenance therapy results in rates of patient satisfaction similar to those for continuous therapy, even though patients experience some symptoms.3,6–8 Survey data suggest that patients take their treatment as required, regardless of the prescribed instructions.9
Advise patients to take a PPI on days when symptoms occur and to return for review if this becomes a continuous requirement. The maximum effect of PPIs may only be reached after repeated doses.10
Prescribe low-dose maintenance therapy
Continuous low-dose PPI maintenance therapy (Table 1) controls symptoms in most people who have completed a 4-week course of standard-dose therapy.3 Avoid supplying standard-strength PPI samples for continuous maintenance therapy unless specifically required.
Communicate the goal and duration of therapy
Tell the patient the goal of initial or ongoing therapy with a PPI
Reassure patients that dyspeptic symptoms are usually benign, respond well to PPI therapy and may resolve after an initial 4-week course that allows healing.
If maintenance therapy is needed in the absence of severe or complicated oesophagitis, explain that the primary purpose is to control symptoms and that the need for therapy will be reviewed every 6–12 months. In severe diagnoses, explain that PPIs are needed continuously to prevent serious complications.
Ask about the duration of therapy when referring for investigation
When referring for endoscopy, request specific details about the need for ongoing therapy. Milder grades of oesophagitis may heal with few residual symptoms after a 4–8-week course of a PPI, while the role of PPIs in non-ulcer dyspepsiaB is limited.
If the indication for ongoing therapy is uncertain, stop the PPI and review
The indication for PPIs prescribed in hospital may be unclear at discharge. If a need for ongoing therapy cannot be established, review before prescribing a further course. If there is a need for maintenance therapy, try stepping down to intermittent, symptom-driven dosing or a low dose (see How to step down PPI therapy, above).B. When reflux, ulcer, and malignancy are absent on endoscopy.
Self-management is effective for mild or intermittent symptoms
Symptoms of dyspepsia are very common, but only about 1 in 6 Australians has consulted a GP about them.11 Mild or intermittent symptoms that do not interfere with daily activities are typically self-managed — strategies include avoiding triggers (which may relate to certain foods or behaviours) and using over-the-counter products such as antacids/alginate or H2 antagonists.
The threshold for clinical management may vary from patient to patient, but consider it:
- if symptoms are of recent onset and do not resolve spontaneously
- if symptoms are severe
- if symptoms occur more than twice a week
- if symptoms recur within 5 days of spontaneous recovery or stopping treatment with antacids/alginate or non-prescription H2 antagonists.
After initial healing, many patients can self-manage even if minor symptoms remain
Studies in uninvestigated dyspepsia have found that 6–12 months after a short course of PPIs for initial symptom control, 20–40% of patients experienced at most mild symptoms and did not require another prescription.4,5
Advise patients to return for review rather than self-manage if they experience alarm symptoms or recurrent troublesome dyspepsia or reflux.
Managing the gastrointestinal adverse effects of NSAIDs
Minimise NSAID use, especially in high-risk patients
Patients aged 65 or more, using anti-coagulants or oral corticosteroids, with serious illness or a history of peptic ulcer are at increased risk of NSAID-related gastrointestinal ulcer complications.12 Consider stopping or reducing the dose of NSAIDs in these patients. Use NSAIDs short term, or intermittently as needed. Paracetamol is first-line for musculoskeletal pain, and may also be used in combination to reduce the required NSAID dose. 13
PPIs reduce NSAID-related dyspepsia but their effectiveness in preventing ulcer complications is uncertain
PPIs and double-dose H2 antagonists reduce the dyspepsia common when using both conventional and COX-2 selective NSAIDs, and reduce the incidence of NSAID-related endoscopically detectable ulcers.14–16 However, it is unknown how well they prevent clinical ulcer complications. Recurrence rates of complicated ulcer are high (5% in 6 months) in patients with a recently healed ulcer who receive an NSAID combined with a PPI.17,18
Consider gastroprotection for high-risk patients only
The benefit of gastroprotection is small in patients without risk factors for ulcer and may not outweigh the costs and harms.2
The recommended gastroprotective strategies are co-prescribing a PPI, double-dose H2 antagonist, or misoprostol with a conventional NSAID, or substituting a COX-2 selective NSAID.2,3 Misoprostolc 800 micrograms daily prevents serious ulcer complications, but may cause diarrhoea and nausea.19 All NSAIDs should be used with caution in patients with cardiovascular risk factors (see NPS RADAR, Aug 05: Elevated cardiovascular risk with NSAIDs?). Concomitant low-dose aspirin eliminates any gastrointestinal safety advantage of COX-2 selective NSAIDs.13
Low-dose aspirin for cardiovascular prevention must be continuous
Low-dose aspirin must be taken continuously to prevent cardiovascular events. To minimise the risk of serious ulcer complications in patients with gastrointestinal risk factors, avoid combining low-dose aspirin with an NSAID. Prescribe aspirin for secondary prevention of ischaemic events or primary prevention when the benefit outweighs the harms (see NPS Prescribing Practice Review 24 — Using antithrombotics: maximising benefits; minimising risks). As with NSAIDs, consider co-prescribing a gastroprotective agent in patients at high risk of ulcer complications.2
Stop NSAIDs in diagnosed peptic ulcer. Prescribe 4–8 weeks' PPI therapy for ulcer healing
Guidelines recommend 4–8 weeks of a standard-dose PPI or double-dose H2 antagonist for ulcer healing.2,3,13 Do not switch to a COX-2 selective NSAID in active peptic ulcer.2 For gastric ulcer, endoscopy is advisable at 6–8 weeks after treatment to confirm healing and exclude malignancy.2
There is some evidence in patients with a history of dyspepsia or ulcer that H. pylori elimination before starting an NSAID can reduce the risk of complicated ulcer.20C. Misoprostol must not be used in pregnancy.
Table 1: Standard and low doses of PPIs2
|PPI||Standard doseD||Low doseD|
20 mg dailyE
20 mg daily
30 mg daily
15 mg daily
omeprazole Acimax, Losec, Meprazol, Omepral, Probitor
20 mg daily
10 mg dailyF
40 mg daily
20 mg daily
20 mg daily
10 mg daily
Dr Peter Wilson, Senior Visiting Specialist, Gastroenterology, Flinders Medical Centre and Repatriation General Hospital, Adelaide, SA
- Gastroenterological Society of Australia. Gastro-oesophageal reflux disease in adults: guidelines for clinicians. 2001. (accessed 24 April 2006).
- Therapeutic Guidelines: Gastrointestinal. Version 3, 2002.
- National Institute for Clinical Excellence. Dyspepsia: management of dyspepsia in adults in primary care. Clinical Guideline No. 17. 2004. (accessed 31 March 2006).
- Armstrong D, et al. Aliment Pharmacol Ther 2005;21:1189–202.
- Meineche-Schmidt V. Am J Gastroenterol 2004;99:1050–8.
- Bour B, et al. Aliment Pharmacol Ther 2005;21:805–12.
- Pace F, et al. Aliment Pharmacol Ther 2005;22:349–56.
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- Hungin AP, et al. Br J Gen Pract 1999;49:451–3.
- McQuaid KR ,Laine L. Clin Gastroenterol Hepatol 2005;3:553–63.
- Westbrook JI ,Talley NJ. Aliment Pharmacol Ther 2003;17:1171–8.
- Wolfe MM, et al. N Engl J Med 1999;340:1888–99.
- Australian Medicines Handbook, 2006.
- Hawkey C, et al. Am J Gastroenterol 2005;100:1028–36.
- Scheiman JM, et al. Am J Gastroenterol 2006;101:701–10.
- Rostom A, et al. Cochrane Database Syst Rev 2002:CD002296.
- Chan FK, et al. Gastroenterology 2004;127:1038–43.
- Lai KC, et al. Am J Med 2005;118:1271–8.
- Silverstein FE, et al. Ann Intern Med 1995;123:241–9.
- Drug Ther Bull 2005;43:37–40.