NSAIDs, analgesia and gastroprotection

01Purpose and principlesWhat the treatment does and how it fits into care.

Analgesia begins with a pain formulation. Inflammatory synovitis may respond to disease control and a short anti-inflammatory bridge; osteoarthritis needs exercise, weight support when relevant and local measures; neuropathic pain needs a separate pathway. Escalating tablets without revisiting diagnosis can mask septic arthritis, fracture, malignancy, cord compression or an inflammatory flare requiring disease-modifying treatment.

NSAIDs inhibit cyclo-oxygenase and reduce prostaglandin production. The same mechanism that reduces inflammatory pain removes gastric mucosal protection, constricts the renal afferent arteriole and alters sodium balance and platelet or vascular biology. Harm is therefore predictable from physiology: ulcer and bleeding, acute kidney injury, hypertension, oedema, heart failure and thrombotic cardiovascular risk. Selective COX-2 inhibition lowers some upper-gut harm but does not remove renal or cardiovascular toxicity.

Route matters. Topical NSAIDs deliver useful local exposure with lower systemic concentrations and are preferred before an oral agent for knee osteoarthritis. They still have contraindications, interactions and systemic adverse effects, particularly when used over large areas, on damaged skin or alongside an oral NSAID. A topical response also does not establish the diagnosis.

Gastroprotection is risk reduction, not permission for indefinite treatment. A proton-pump inhibitor should accompany an oral NSAID in osteoarthritis, and is particularly important with older age, previous ulcer, anticoagulant, antiplatelet or corticosteroid exposure. Previous complicated ulcer or active bleeding usually makes avoidance the safer plan; when an anti-inflammatory is indispensable, involve gastroenterology or the responsible specialist and address Helicobacter pylori where relevant.

Renal risk rises during vomiting, diarrhoea, fever, fasting or poor intake and with chronic kidney disease, heart failure, cirrhosis or diuretics. The combination of an NSAID, renin-angiotensin-system blocker and diuretic can markedly reduce filtration. Baseline creatinine alone is not reassurance: give a sick-day stop instruction and arrange repeat renal function after initiation or dose change in people at risk.

Cardiovascular selection is individual. All systemic NSAIDs can raise blood pressure and cause fluid retention; diclofenac and high-dose ibuprofen have less favourable thrombotic profiles, while naproxen is often chosen when an NSAID is unavoidable in someone with cardiovascular risk, but it remains a gastrointestinal and renal toxin. Active heart failure, recent vascular events or uncontrolled hypertension should usually prompt avoidance and alternative pain management.

Pregnancy requires a separate discussion. MHRA advises avoiding systemic NSAIDs from 20 weeks unless clinically necessary because prolonged exposure can reduce fetal urine and amniotic fluid and can constrict the ductus arteriosus; use the lowest dose for the shortest time with monitoring when exposure continues beyond several days. The low-dose aspirin used for obstetric indications is not interchangeable with analgesic-dose NSAID advice and should not be stopped without the maternity team.

Key points

Treat the cause and function, not the pain score alone: define whether pain is inflammatory, mechanical, neuropathic, referred or an emergency before choosing an analgesic.
First-line for knee osteoarthritis is a topical NSAID alongside therapeutic exercise; consider topical treatment for other joints before exposing the whole body to an oral NSAID.
When oral NSAID treatment is necessary, use the lowest effective dose for the shortest possible time and co-prescribe a proton-pump inhibitor while the NSAID is taken.
Do not combine oral NSAIDs, and count over-the-counter ibuprofen, cold remedies and topical products during medicine reconciliation.
A proton-pump inhibitor reduces upper gastrointestinal ulcer risk but does not prevent NSAID-associated acute kidney injury, fluid retention, cardiovascular events or lower-gastrointestinal injury.
Check previous ulcer or bleed, age and frailty, anticoagulants or antiplatelets, corticosteroids, kidney disease, dehydration, hypertension, heart failure, cardiovascular disease, asthma and pregnancy before prescribing.
Paracetamol has limited benefit for osteoarthritis and should not be a routine long-term substitute; NICE reserves it or a weak opioid for infrequent short-term use when other pharmacological options are ineffective or contraindicated.
Avoid strong opioids for osteoarthritis; if an opioid is exceptionally used, state the goal, duration, driving advice, constipation plan, review date and stop rule.
From 20 weeks of pregnancy, systemic NSAIDs should be avoided unless clinically necessary and then used briefly with obstetric advice; they are contraindicated in the final trimester under product information.
Reassess benefit within days to weeks: if pain and function have not meaningfully improved, stop the medicine rather than accumulating toxicity.

02Indications, selection and cautionsWho may benefit, who needs urgent treatment and important alternatives.

Inflammatory pain

Prolonged morning stiffness, swelling, warmth, rest pain and improvement with movement suggests inflammation that needs disease-specific assessment rather than analgesia alone.

Mechanical pain

Load-related pain, brief stiffness, crepitus and activity limitation without systemic features supports a rehabilitation-led plan in which medicine enables movement rather than replaces it.

Upper gastrointestinal toxicityRed flag

Dyspepsia is an unreliable warning; ulcer bleeding may first present with melaena, haematemesis, syncope or iron-deficiency anaemia, especially in older or anticoagulated patients.

Renal and fluid toxicityRed flag

Reduced urine, weight gain, oedema, worsening blood pressure, breathlessness or an intercurrent dehydrating illness should trigger NSAID cessation and renal or cardiac assessment.

Respiratory hypersensitivityRed flag

Bronchospasm, nasal symptoms, urticaria or angioedema after aspirin or another NSAID predicts cross-reactive risk and requires an allergy-aware alternative plan.

Analgesic dependence pattern

Increasing dose, early repeat requests, sedation, falls, constipation or use for distress rather than episodic pain signals opioid harm and need for structured review.

Red flags requiring action

Vomiting blood, black stools, collapse, unexplained anaemia or a rigid tender abdomen requires urgent assessment for gastrointestinal haemorrhage or perforation.
New oliguria, confusion, dehydration, rising creatinine or hyperkalaemia after an NSAID requires immediate withdrawal and acute kidney injury assessment.
Acute dyspnoea, orthopnoea, chest pain, marked oedema or uncontrolled blood pressure may reflect fluid retention, heart failure or a cardiovascular event.
Wheeze, facial swelling, urticaria or hypotension soon after dosing suggests NSAID hypersensitivity and must be treated as an airway emergency when severe.
Pain that is nocturnal, progressive, associated with fever, a hot swollen joint, neurological loss, trauma or cancer features needs diagnosis rather than repeated analgesic escalation.
Any NSAID exposure from 20 weeks of pregnancy warrants obstetric and prescribing review because prolonged use can cause oligohydramnios and fetal ductal effects.

03Assessment before treatmentTests and checks that guide safe selection.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line clinical and medicine reviewFirst stepFirst line
Why
Establish the pain mechanism, functional target and every prescription or non-prescription analgesic before adding treatment.
Interpretation and limitations
Document joint examination, red flags, previous response and harm, alcohol, driving, pregnancy possibility and concurrent anticoagulant, antiplatelet, steroid, ACE inhibitor, ARB, diuretic and serotonergic medicines.
02
Baseline renal function and electrolytes
Why
Estimate NSAID susceptibility and create a comparator before systemic treatment in anyone with renal, cardiovascular, frailty or dehydration risk.
Interpretation and limitations
A normal result does not prevent haemodynamic acute kidney injury during illness. Avoid or seek specialist advice with important chronic kidney disease and repeat after initiation when risk is material.
03
Blood pressure, weight and fluid status
Why
Detect hypertension or congestion that an NSAID may worsen.
Interpretation and limitations
Uncontrolled pressure, oedema or decompensated heart failure changes the risk-benefit decision; a later weight rise or breathlessness is a stop signal, not a reason to add diuretic automatically.
04
FBC and gastrointestinal risk assessment
Why
Identify baseline anaemia and decide whether oral NSAID exposure is acceptable.
Interpretation and limitations
Previous ulcer complication, current bleeding, falling haemoglobin or multiple antithrombotic drugs strongly favour avoidance; a PPI cannot neutralise all risk.
05
Pregnancy and reproductive assessment
Why
Prevent fetal exposure during the gestational periods in which NSAID risk changes.
Interpretation and limitations
Ask gestation and obstetric indication explicitly. From 20 weeks avoid systemic NSAIDs unless necessary; final-trimester use is contraindicated in the naproxen product information.
06
Cause-directed imaging or sampling
Why
Investigate pain whose pattern suggests infection, fracture, malignancy or inflammatory disease rather than simple symptomatic treatment.
Interpretation and limitations
A hot swollen joint generally needs urgent aspiration; focal trauma may need radiography, and neurological or malignant red flags need the corresponding emergency pathway.

04Treatment approachPreparation, options, escalation and aftercare.

01First-line local strategyStart with diagnosis, movement and topical treatmentFirst stepFirst lineLocalised peripheral joint pain has no emergency feature and topical treatment is suitable.

1Agree a measurable function such as walking, sleep or hand use and begin exercise, load modification, physiotherapy or disease-specific therapy.
2For knee osteoarthritis offer a topical NSAID first; apply the licensed amount to intact skin and avoid simultaneous oral NSAID exposure.
3Review local skin reaction, actual use and functional benefit; stop if benefit is absent rather than adding systemic exposure automatically.

02Oral escalationUse the shortest protected NSAID trialEscalationTopical treatment is ineffective or unsuitable and inflammation or pain justifies systemic anti-inflammatory exposure.

1Reconcile contraindications and interactions, record renal function and blood pressure where risk warrants, and discuss pregnancy, bleeding and sick-day interruption.
2Choose one oral NSAID at the lowest effective dose for the shortest duration and co-prescribe a PPI for the period of NSAID use.
3Set an early benefit-and-harm review with a stop date; recheck renal function and pressure after initiation or illness in susceptible patients.

03High-risk alternativeAvoid systemic NSAIDs and reformulate painAlternativePrevious ulcer bleed, advanced kidney disease, decompensated heart failure, major cardiovascular risk, anticoagulation, NSAID hypersensitivity or later pregnancy makes harm disproportionate.

1Treat active inflammatory disease, infection or structural pathology and maximise physical, topical and non-pharmacological options.
2Consider a short, explicitly bounded paracetamol rescue only when appropriate; adjust the maximum for weight, liver, nutrition and alcohol factors.
3Use weak opioid treatment only exceptionally after shared goals and safety planning, and avoid strong opioids for osteoarthritis.

04Toxicity responseStop exposure and treat the syndromeBleeding, renal decline, fluid overload, hypersensitivity or significant fetal exposure occurs.

1Stop all oral and over-the-counter NSAIDs, assess severity and arrange urgent hospital care for haemorrhage, perforation, anaphylaxis, severe kidney injury or heart failure.
2Correct volume, interacting medicines and organ complications under the relevant acute-care pathway; document the reaction clearly across records.
3AlternativeAfter recovery, choose an alternative mechanism and preventive plan rather than simply switching to another NSAID in the same risk context.

05Regimens, contraindications and interactionsTreatment details and the circumstances that modify them.

A first-line local NSAID option for knee osteoarthritis and a short trial for concordant superficial musculoskeletal pain.

Diclofenac 1.16% gel

For adults and adolescents aged 14 years or over, apply 2–4 g to the painful area three or four times daily, according to area size, for no more than seven days without medical advice under this product licence.

Do not use on broken skin, in NSAID hypersensitivity, or with occlusion; wash hands, avoid eyes and excessive sunlight, and count systemic exposure if another NSAID is prescribed.

An oral NSAID example when a systemic anti-inflammatory is justified after individual gastrointestinal, renal and cardiovascular assessment.

Naproxen

A common adult inflammatory-pain regimen is 250–500 mg orally twice daily with or after food; use the lowest effective dose for the shortest course and stay within the indication-specific product maximum.

Avoid active ulcer or bleeding, severe kidney, liver or heart failure, aspirin-sensitive asthma and the final trimester of pregnancy; review anticoagulants, antiplatelets, ACE inhibitors, ARBs, diuretics and lithium.

Proton-pump-inhibitor gastroprotection accompanying oral NSAID treatment, including the NICE osteoarthritis pathway.

Omeprazole

Give 20 mg orally once daily while an oral NSAID is being taken for NSAID-associated ulcer prevention in an at-risk adult; duration should follow the NSAID exposure and clinical indication.

It does not protect kidneys or the cardiovascular system; review long courses for indication, interaction, magnesium or B12 deficiency, enteric infection and rebound symptoms when stopping.

A short rescue option when anti-inflammatory treatment is unsuitable, recognising limited routine benefit in osteoarthritis.

Paracetamol

Adults usually take 500–1000 mg orally every 4–6 hours as required, leaving at least four hours between doses and not exceeding 4 g in 24 hours; use a lower maximum when weight, nutrition, liver disease or alcohol increases risk.

Count all combination products; overdose can be initially asymptomatic and needs urgent toxicology assessment. Frail adults under 50 kg or those with hepatic risk require an individual lower ceiling.

A weak opioid rescue only when safer options are ineffective or contraindicated and a specific functional goal justifies exposure.

Codeine

If exceptionally selected, a licensed adult dose is 30–60 mg orally every four hours as needed, not exceeding 240 mg in 24 hours; use the smallest quantity for the shortest planned interval.

Avoid in respiratory depression and breastfeeding, and review sedation, driving, alcohol, constipation, falls, dependence, CYP2D6 variability and concurrent sedatives; do not use as routine long-term osteoarthritis treatment.

06Complications, monitoring and follow-upAdverse effects, response and longer-term review.

Within the planned trial, compare the agreed functional target and pain pattern with baseline; discontinue an NSAID or opioid that has not produced a worthwhile benefit.
For systemic NSAID use in a susceptible person, repeat creatinine, eGFR, potassium and blood pressure soon after initiation or dose change and after any dehydrating illness, using local timing matched to risk.
Ask specifically about melaena, haematemesis, dyspepsia, oedema, breathlessness, reduced urine, wheeze, rash, dizziness, falls and non-prescription analgesics rather than relying on a generic side-effect question.
Reassess the need for both NSAID and PPI at every repeat; avoid leaving gastroprotection on indefinitely after the causal NSAID has stopped unless another indication remains.
Track opioid quantity, early requests, alertness, driving, bowel function and dependence indicators; taper a prolonged course collaboratively rather than abruptly unless immediate toxicity requires withdrawal.
If pregnancy occurs or gestation reaches 20 weeks, reconcile every prescribed and over-the-counter NSAID promptly and involve maternity care when exposure was prolonged or clinically necessary.

07Special situationsVariants, exceptions and circumstances that change the usual approach.

PPI protection is compartment-specific

It lowers upper-gastrointestinal acid-related injury but cannot reverse renal prostaglandin loss, sodium retention or cardiovascular thrombosis.

Topical is lower exposure, not zero exposure

Large treatment areas, damaged skin, frequent application and concurrent oral dosing increase systemic absorption and adverse-effect risk.

Dyspepsia does not predict bleeding

A patient can have discomfort without an ulcer or a major silent ulcer that first presents with anaemia or haemorrhage.

The triple whammy is physiological

Diuretic-related volume reduction, efferent vasodilation from ACE inhibition or ARB treatment and NSAID-mediated afferent constriction can collapse filtration.

Low-dose aspirin is a different indication

Obstetric or vascular antiplatelet aspirin should not be stopped merely because analgesic-dose NSAID restrictions are discussed.

Analgesia should unlock rehabilitation

If medicine does not improve movement, sleep or participation enough to justify its harms, a lower pain number alone is not a durable treatment success.

08Common pitfallsFrequent interpretation and management errors.

01
Prescribing an oral NSAID before checking non-prescription ibuprofen, anticoagulants, kidney function, blood pressure, ulcer history and pregnancy.
02
Adding a proton-pump inhibitor and describing the NSAID as safe despite unresolved renal, cardiovascular, lower-gut and hypersensitivity risks.
03
Using two NSAIDs together or adding oral treatment to extensive topical use without recognising cumulative systemic exposure.
04
Allowing repeat naproxen, paracetamol or codeine indefinitely without a functional target, review interval and stop rule.
05
Treating severe or changing pain as a dose problem when sepsis, fracture, malignancy, neurological compression or active inflammatory disease has not been excluded.
06
Applying the final-trimester warning only and overlooking MHRA advice about oligohydramnios and ductal effects from prolonged systemic NSAID use after 20 weeks.