10.1.1. NSAIDs

Click here for gastro protection

ChoiceDrugDosage
1st choiceIbuprofen tablets 200mg, 400mg, 600mg; suspension 100mg/5mLDose:
Initially 200-400mg 3-4 times daily; increased if necessary to max 2.4g daily; maintenance dose of 0.6-1.2g daily may be adequate if symptoms permit
Or
Naproxen tablets 250mg, 500mgDose:
Rheumatic disease, 0.5-1g daily in 1-2 divided doses

Acute musculoskeletal disorders, 500mg initially, then 250mg every 6-8 hours as required; max dose after first day 1.25g

Acute gout, 750mg initially, then 250mg every 8 hours until attack has passed

2nd choice
(if naproxen not tolerated or treatment failure)

2nd line choice is not definitive and will depend on individual patient factors and safety factors of individual NSAIDs. Please see Prescribing Notes below for further information

Prescribing Notes

  • Differences in anti-inflammatory activity between NSAIDs are small, but there is considerable variation in individual response and tolerance to these drugs. About 60% of patients will respond to any NSAID; of the others, those who do not respond to one may well respond to another.
  • When considering a 2nd line choice for patients with a high risk of cardiovascular complications, diclofenac, etoricoxib and high dose ibuprofen (>1200mg/day) should be avoided.
  • When considering a 2nd line choice for patients at risk of gastrointestinal complications, all non-selective NSAIDs should be avoided. Celecoxib is a cost-effective option if a Cox-2 inhibitor is required.
  • All NSAIDs should generally be used at the lowest effective dose and for the shortest period of time necessary to control symptoms.
  • Low-dose ibuprofen (≤1200mg per day) is an appropriate first choice NSAID in view of its low risk of gastrointestinal (GI) and cardiovascular (CV) side effects.
  • Consider prescribing a PPI with any NSAID to reduce the risk of adverse GI effects, particularly in those who are at high GI risk (includes anybody aged 65 years or older) and long-term NSAID users.
  • Ibuprofen may interfere with the cardioprotective effects of low dose aspirin when taken concomitantly. Aspirin should be taken 1 to 2 hours before ibuprofen. Risk may be greater in those taking regular, rather than intermittent, ibuprofen. Naproxen may be a suitable alternative .

Side Effects

  • All NSAIDs carry the risk of side effects, which can be serious and life-threatening. Although the risks may vary between individual NSAIDs, important side effects include GI complications (e.g. perforation, ulcer, bleeding) , CV (e.g. stroke, myocardial infarction) and renal (e.g. deterioration of renal function, renal failure).

General Cautions

  • Relative contra-indications to NSAIDs include cerebrovascular disease, cardiovascular disease, heart failure, hypertension, renal impairment, peptic ulceration; absolute contra-indications include proven hypersensitivity to aspirin or any NSAID. Cautions and contra-indications vary between drugs so please refer to BNF and/or product literature.
  • NSAIDs may worsen asthma in patients who are susceptible; they are contra-indicated if aspirin or any other NSAID has precipitated attacks of asthma.
  • NSAIDs should be used with caution in the elderly (risk of serious side-effects and fatalities).

Renal/Hepatic Risk

  • NSAIDs should be avoided if possible or used with caution in patients with renal impairment; the lowest effective dose should be used for the shortest possible duration, and renal function should be monitored. Avoid in severe renal impairment.
  • Caution in elderly patients in whom impaired renal function may be expected, particularly when they are ill or dehydrated.
  • Caution in patients taking diuretics.
  • During an acute illness, consider temporarily stopping NSAID in order to reduce the risk of acute kidney injury (‘sick day guidance’). For further info visit Think Kidneys website.
  • NSAIDs should be used with caution in patients with hepatic impairment and avoided in severe liver disease. 

CV Risk

  • All NSAID use can, to varying degrees, be associated with a small increased risk of thrombotic events (e.g. myocardial infarction and stroke) independent of baseline cardiovascular risk factors or duration of NSAID use; however, the greatest risk may be in those receiving high doses long term.
  • Cox-2 inhibitors, diclofenac (150 mg daily) and ibuprofen (2.4 g daily) are associated with an increased risk of thrombotic events.
  • The increased risk for diclofenac is similar to that of licensed doses of etoricoxib. Naproxen (1 g daily) is associated with a lower thrombotic risk, and low doses of ibuprofen (1.2 g daily or less) have not been associated with an increased risk of myocardial infarction.
  • Etoricoxib may be associated with more frequent and severe effects on blood pressure than some other cox-2 inhibitors and traditional NSAIDs. Etoricoxib is contraindicated in patients with BP persistently >140/90mmHg. Hypertension should be controlled before treatment with etoricoxib is started, and BP should be monitored within two weeks after initiation, after six weeks and periodically thereafter.
  • Prescribing information has been updated to introduce a lower recommended dose of etoricoxib 60mg daily for patients with rheumatoid arthritis or ankylosing spondylitis (see MHRA).
  • All NSAIDs are contra-indicated in severe heart failure.

GI Risk

  •  Cox-2 inhibitors are associated with a lower GI risk than traditional NSAIDs. However, their GI-safety advantage is diminished when co-administered with aspirin.
  • Of the traditional NSAIDs, diclofenac and naproxen are associated with moderate GI risk and ibuprofen (may be related to dose) with the lowest risk.
  • There is no robust evidence that prescribing a cox-2 inhibitor plus a PPI offers any significant advantage over prescribing a traditional NSAID plus a PPI in preventing GI complications.
  • Where a cox-2 inhibitor is indicated, celecoxib is a cost-effective option.
  • While it is preferable to avoid NSAIDs in patients with active or previous GI ulceration or bleeding, and to withdraw them if GI lesions develop, nevertheless patients with serious rheumatic diseases (e.g. rheumatoid arthritis) are usually dependent on NSAIDs for effective relief of pain and stiffness. Patients at risk of GI adverse effects (including the elderly), who need NSAID treatment should receive gastroprotective treatment. Refer to boxes below:

Which patients are at high risk of GI adverse effects?
One or more of the following risk factors:

· Aged 65 years or older.

· History of gastroduodenal ulcer, GI bleeding, or gastroduodenal perforation.

· Serious comorbidity, such as cardiovascular disease, hepatic or renal impairment (including dehydration), diabetes, or hypertension.

· Presence of Helicobacter pylori infection.

· Concomitant use of medications that are known to increase the risk of GI bleeds, e.g. aspirin (even 75mg/day), warfarin, NOACs, corticosteroids, SSRIs.

·   A requirement for prolonged NSAID use, including people with:

o    Osteoarthritis or Rheumatoid Arthritis of any age

o    45 years of age or older with chronic low back pain

 
What dose of PPI should I prescribe for gastroprotection* for a NSAID?
Lansoprazole**15–30 mg once daily
Omeprazole**20 mg once daily
Esomeprazole20 mg once daily
Pantoprazole20 mg once daily
RabeprazoleNot licensed for this indication

*Prescription directions to include the instruction “ while taking [named NSAID]”
** NI Formulary Choices