Non-steroidal anti-inflammatory drugs (NSAIDS)

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GENERAL CONSIDERATIONS

• Peri-operative period: refer to ‘Acid suppression therapy’ below.
• Prescribe only one NSAID at any one time (excluding low-dose aspirin). This includes topical preparations. 
• Upper gastro-intestinal bleeding and ulceration occurs irrespective of the route of administration. The first indication of damage may be life-threatening complications. The risk of bleeding markedly increases after 5 days of treatment, especially in older people.
• Consider other methods of management before resorting to NSAIDs, eg intra-articular corticosteroid for acute gout, lifestyle advice and simple analgesics for osteoarthritis.
• There is no league table of efficacy or strength of NSAID and response seems to vary between individuals. Toxicities however do vary between preparations:
  • ibuprofen in low dose (up to 1·2 grams/day) has the lowest risk of gastro-intestinal toxicity compared to naproxen, diclofenac and indomethacin.
  • celecoxib is associated with reduced gastro-intestinal risk relative to most NSAIDs at equivalent doses.
  • all NSAIDs, including cyclo-oxygenase-2-selective (COX-2) inhibitors, are relatively contra-indicated in those with previous peptic ulcer disease. 
  • diclofenac can cause alteration in liver function tests and even hepatic necrosis; periodic checks of liver function are therefore required. Diclofenac should be withdrawn in cases of elevation of hepatic enzymes even when thought to be due to other therapy, eg DMARDs.
• The use of modified-release preparations is not recommended as sustained high levels may be associated with increased gastro-intestinal toxicity, similar to the effect of NSAIDs with a long half-life. They are only recommended when compliance is in doubt and could be improved by once-daily dosing.
• Review the continued use of NSAIDs on a regular basis – when inflammatory arthritis is in remission or a state of low disease activity then a trial of withdrawal of NSAID should always be attempted. 
• Withdraw NSAIDs if patients develop worsening renal impairment. When NSAIDs are commenced in patients with pre-existing renal impairment check U&Es 1 to 2 weeks after initiation and periodically thereafter.
• Where possible avoid the concomitant use of NSAID and ACE inhibitor or angiotensin-II receptor antagonist. In this scenario U&Es should be checked 1 to 2 weeks after initiation and periodically thereafter.
• NSAIDs may lead to hypertension and increase cardiovascular risk. All NSAIDs, both unselective and cyclo-oxygenase-2-selective (COX-2) inhibitors, have a similar risk although naproxen and low-dose ibuprofen (up to 1·2 grams/day) appear to have a lower thrombotic risk than other NSAIDs, or COX-2 inhibitors. Diclofenac is associated with an increased risk of thrombotic events.
• There is a two-fold risk of hospitalisation for congestive cardiac failure when using NSAIDs in older people or those with existing heart failure.

CONTRA-INDICATIONS

USE WITH CAUTION*

known sensitivity to aspirin or other NSAID recent history of peptic ulcer disease patients with poorly-controlled asthma (including patients requiring oral steroids)  moderate to severe renal impairment (eGFR less than 30) severe congestive cardiac failure requiring high-dose diuretics poorly-controlled hypertension bleeding problems, eg low platelets, known coagulopathy, on heparin infusion or high-dose enoxaparin severe liver dysfunction poorly-controlled diabetes  pregnancy severe pregnancy-induced hypertension with proteinuria avoid in patients taking certain drugs, eg mifepristone.

mild to moderate renal impairment (eGFR less than 60) if eGFR less than 45 seek senior medical advice before use renal transplant patients with good function older patients (over 65 years) diabetes patients with inflammatory bowel disease (flare can be induced) peripheral vascular disease or treated cardiac failure after hepatobiliary, renal or major vascular surgery patients taking: diuretics, especially potassium-sparing ACE inhibitors, angiotensin-II receptor antagonists ciclosporin lithium – lithium toxicity may occur see BNF for other drug interactions. see ‘Sick day rule’ card correct dehydration, hypovolaemia and large blood losses prior to starting NSAIDs.

*In all of these patients where caution is advised, consider reducing the frequency of the NSAID and monitor renal function regularly.  Any increasing trend in plasma urea, creatinine or potassium is an indication for stopping the NSAID.

Gastroprotection

The following patients are at increased risk of GI complications. If an NSAID is considered absolutely necessary they should be co-prescribed lansoprazole or omeprazole (section 1.3):

• age over 75 years
• concomitant use of medicines known to increase risk of GI bleeds (ie anticoagulants, aspirin, corticosteroids, SSRIs, venlafaxine, duloxetine)
• history of GI ulcer/bleeding
• excessive alcohol/smoking.