01Core principlesThe concepts and mechanisms needed to understand the subject.
NSAIDs impair gastroduodenal defence by inhibiting prostaglandin synthesis and can cause topical epithelial injury. Risk is not uniform. Previous complicated ulcer is highly consequential; advancing age, high dose, multiple NSAIDs, aspirin, anticoagulants, corticosteroids, smoking and H pylori add further risk. Dyspepsia is a poor safety monitor because a dangerous ulcer can bleed without warning pain.
Prevention has three layers. Avoid an unnecessary NSAID or use intermittent topical and non-pharmacological alternatives where appropriate. If an oral NSAID is needed, minimise dose and duration. In a patient at upper-GI risk, add an evidence-based PPI such as omeprazole 20 mg once daily. A COX-2-selective NSAID may reduce ulcer risk but can be unsuitable when cardiovascular risk is high.
Gastroprotection does not neutralise systemic toxicity. NSAIDs constrict the afferent arteriole, worsen sodium retention and interact with diuretics, renin-angiotensin blockers, anticoagulants and methotrexate. Review the person after initiation and whenever illness causes dehydration. When an ulcer occurs, stop the NSAID if possible, test for H pylori and heal the lesion before deciding whether any anti-inflammatory drug should return.
Key points
- Start with the pain diagnosis and non-drug measures; an NSAID without meaningful functional benefit creates risk without therapeutic justification.
- Use the lowest effective NSAID dose for the shortest necessary time and avoid simultaneous prescribed and over-the-counter products.
- NICE advises stopping the NSAID where possible when a peptic ulcer is diagnosed and treating with full-dose PPI or H2-receptor antagonist for eight weeks.
- If anti-inflammatory therapy must continue after healing, reconsider a COX-2-selective agent and add gastroprotection, while assessing cardiovascular contraindications separately.
- For an at-risk adult using an NSAID, the current omeprazole SmPC specifies 20 mg orally once daily for prevention of gastric and duodenal ulcer.
- Review renal function, blood pressure, oedema, haemoglobin and ongoing analgesic benefit; protection is an active plan rather than a permanent repeat-prescription default.
02Mechanisms and patternsImportant relationships and how to distinguish them.
Previous ulcer haemorrhage or perforation predicts substantially greater harm from renewed NSAID exposure.
A patient can develop occult blood loss or sudden haemorrhage without preceding dyspepsia.
Rising creatinine, oliguria, oedema or hypertension may occur despite complete absence of gastric symptoms.
Melaena, haematemesis, postural symptoms or shock requires immediate upper-GI bleeding assessment.
A prescribed NSAID plus an over-the-counter cold or pain product can unintentionally raise total dose and toxicity.
03Interpreting evidenceInformation, measurements and their limitations.
Consider the information, its meaning and its limitations before deciding what follows.
- 01
Medicine reconciliation - Why
- Identify all NSAIDs, aspirin, antithrombotics, corticosteroids and interacting drugs.
- Interpretation and limitations
- Ask explicitly about ibuprofen and combination products because electronic prescriptions omit non-prescribed exposure.
- 02
Full blood count and ferritin - Why
- Detect overt or occult NSAID-related blood loss.
- Interpretation and limitations
- A falling haemoglobin or depleted ferritin requires source investigation rather than empiric iron alone.
- 03
Renal function and electrolytes - Why
- Measure baseline and treatment-emergent renal toxicity.
- Interpretation and limitations
- Changes after dehydration or addition of a diuretic or renin-angiotensin blocker can require NSAID cessation.
- 04
H pylori testing - Why
- Find a cofactor that can be eradicated in ulcer disease.
- Interpretation and limitations
- Use valid PPI and antibiotic washouts; eradication does not make high-dose chronic NSAID exposure harmless.
- 05
Upper-GI endoscopy - Why
- Diagnose ulcer, bleeding stigma or another lesion when symptoms or anaemia warrant it.
- Interpretation and limitations
- Biopsy a gastric ulcer and confirm healing because NSAID attribution can conceal cancer.
04Applied reasoningWorked examples connecting principles to decisions.
01Worked case: prevention before prescribingProtect a patient who truly needs treatmentA 72-year-old with a previous uncomplicated gastric ulcer needs a short course of anti-inflammatory treatment for an acute crystal arthritis flare after other measures are considered unsuitable.+
- 1Confirm the inflammatory indication, reconcile aspirin and over-the-counter NSAIDs, check renal function and blood pressure, and recognise age plus previous ulcer as upper-GI risk.
- 2Select the lowest effective anti-inflammatory dose for the shortest planned course and prescribe omeprazole 20 mg orally once daily during exposure rather than waiting for dyspepsia.
- 3At the planned one-week review the flare has settled, renal function and haemoglobin are unchanged and no melaena or epigastric pain has occurred, so the NSAID is stopped rather than renewed automatically.
- 4Verify that omeprazole duration is reviewed after NSAID cessation and that the patient understands to avoid duplicate over-the-counter ibuprofen or naproxen.
02Ulcer despite treatmentStop injury and heal tissueEndoscopy finds a gastric ulcer after three months of naproxen in a patient who did not receive gastroprotection.+
- 1Stop naproxen where possible and obtain adequate gastric biopsies plus valid H pylori testing.
- 2Give eight weeks of full-dose acid suppression under NICE guidance and eradicate H pylori if present.
- 3Replace the analgesic strategy using non-NSAID and non-pharmacological options before considering renewed exposure.
- 4Repeat endoscopy to prove gastric-ulcer healing and reassess cardiovascular and renal risk before any future NSAID.
03Intercurrent dehydrationPrevent compounded renal harmA person taking an NSAID, ACE inhibitor and diuretic develops vomiting with reduced urine output.+
- 1Assess volume status, creatinine, potassium and the continuing indication for each medicine urgently.
- 2Withhold the NSAID and manage dehydration and acute kidney injury according to severity.
- 3Avoid assuming the PPI offers renal protection because its effect is confined mainly to upper-GI injury.
- 4Recheck renal recovery and use an alternative pain plan before discharge.
05Relevant medicines and safetySpecific regimens and precautions where medicines are relevant.
Omeprazole for NSAID-ulcer prevention
For an adult at risk of NSAID-associated gastric or duodenal ulcer, give omeprazole 20 mg orally once daily while the ulcerogenic exposure remains necessary, using the current 20 mg capsule SmPC. Review and stop unnecessary NSAID and PPI treatment rather than allowing either prescription to continue indefinitely. Administer the prevention capsule each morning with water and swallow it whole; chewing or crushing destroys the protected pellets.Exclude active ulcer or bleeding when symptoms, anaemia or melaena are present. In hepatic impairment the SmPC states 10–20 mg daily may be sufficient. Review the nelfinavir contraindication, clopidogrel interaction, acute interstitial nephritis, enteric infection and longer-term hypomagnesaemia, B12 deficiency and fracture risk. Protection is incomplete when multiple antithrombotic or ulcer risks coexist. No dose adjustment is required solely for renal impairment.
06Checking understandingVerify the reasoning, revisit uncertainties and apply feedback.
- Review pain and function soon after initiation so ineffective NSAID therapy is stopped.
- Check renal function and blood pressure after starting or dose escalation in patients at renal or cardiovascular risk.
- Ask directly about melaena, haematemesis, epigastric pain and over-the-counter duplicate exposure.
- Measure full blood count or ferritin when occult loss, fatigue or long-term exposure is plausible.
- Review the PPI indication after NSAID cessation and retain it only for a separate continuing reason.
07Special situationsVariants, exceptions and circumstances that change the usual approach.
Symptoms do not predict bleeding
NSAID ulcers can erode an artery before producing enough local inflammation to cause warning dyspepsia.
PPI protection is compartment-specific
Reduced gastric acidity cannot prevent afferent arteriolar constriction, sodium retention or platelet-related cardiovascular events.
COX-2 is a trade-off
Lower gastroduodenal injury for some patients must be weighed against cardiovascular disease, dose and duration.
The stop date prevents harm
A deliberately short course with a review date is safer than an open repeat prescription labelled as needed.
08Common pitfallsFrequent interpretation and management errors.
- 01
Adding a PPI but leaving two concurrent NSAIDs on the medicine list.
- 02
Using absence of dyspepsia as evidence that an ulcer has not formed.
- 03
Ignoring renal and cardiovascular toxicity after gastroprotection begins.
- 04
Continuing both NSAID and PPI after the painful inflammatory episode resolves.