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10.1.1 Non-steroidal anti-inflammatory drugs

10.1.1 Non-steroidal anti-inflammatory drugs

10.1.1 Non-steroidal anti-inflammatory drugs (NSAIDs)

First line treatment
GREEN      Ibuprofen [Consider OTC/Self care] 
                   tablets 200mg, 400mg, 600mg
                     syrup 100mg/5mL  
GREEN      Naproxen [Consider OTC/Self care]              
                  tablets  250mg, 500mg      
 
Gastrointestinal toxicity and cardiovascular toxicity are the two most important safety concerns for non-steroidal anti-
inflammatory drugs (NSAIDs) and COX-2 inhibitors (coxibs). Clinical trial and epidemiological data have given important
information on the level of risk with individual medicines. However, these data are complex and there are no robust 
comparisons for many NSAIDs. Most evidence relates to the coxibs, naproxen, ibuprofen, and diclofenac.  The National
Prescribing Centre (NPC) has summarised up-to-date prescribing advice and information in relation to NSAIDs, which is 
available through their website (www.npc.nhs.uk).
 
Thrombotic risks
In October 2006, the Commission on Human Medicines (CHM) gave advice on the latest evidence for cardiovascular thrombotic
risks: 
          >     Diclofenac 150 mg daily has a thrombotic risk profile similar to that of at least one coxib (etoricoxib) and possibly others
          >     Naproxen 1000 mg daily has a lower thrombotic risk than coxibs and, overall, epidemiological data do not suggest an 
                 increased risk of myocardial infarction
          >     For ibuprofen at high doses (eg, 2400 mg daily) there may be a small thrombotic risk, but at lower doses (eg, 1200 mg 
                 daily 
          >     For less) epidemiological data do not suggest an increased risk of myocardial infarction
 
Less evidence is available for other NSAIDs, but they may be associated with a small risk of thrombotic events, especially with long 
duration of treatment and high doses.
 
Cardiovascular risks
Results of two recently published epidemiological studies lend support to the view that some increase in thrombotic cardiovascular
risk may apply to all NSAID users, irrespective of their baseline risk, and not only to chronic users. The absolute increase in risk for 
'healthy' users is very low. Current advice remains that patients should use the lowest effective dose and the shortest duration of 
treatment necessary to control symptoms. Overall evidence continues to indicate that naproxen is associated with a lower 
thrombotic risk than coxibs. For ibuprofen, no significant increase in risk has been identified for doses of up to 1200mg daily.
Reference: Drug Safety Update, Volume 2 Issue 7, February 2009.
 
Gastrointestinal risks
The Committee on Safety of Medicines (now the Commission on Human Medicines) has reviewed the relative gastrointestinal risks 
of NSAIDs on several occasions.  Recently, we have highlighted the high gastrointestinal risks with piroxicam, ketoprofen, and 
ketorolac.  Of the traditional NSAIDs, low-dose ibuprofen offers the lowest risk. Coxibs are associated with reduced gastrointestinal
risk relative to most NSAIDs at equivalent doses. However, coxibs (like NSAIDs) may vary in their effects, and evidence for a 
reduction in the most clinically important gastrointestinal risks for etoricoxib is weak.  Proton pump inhibitors reduce the
gastrointestinal risks associated with NSAIDs, and may reduce the risks to a similar level as use of a coxib alone.
 
Other NSAIDs 
GREEN      Diclofenac 
                   injection 25mg/mL
                   suppositories 12.5mg, 25mg, 50mg, 100mg
GREEN      Mefenamic acid 
                   capsules 250mg
                   tablets 500mg   
 
Indometacin is usually recommended only for ankylosing spondylitis and gout.
GREEN      Indometacin 
                   capsules 25mg, 50mg    
                   suppositories 100mg
 
Patients over 65 years who are in high risk groups for developing ulcers (history of peptic ulcer or bleeding, cardiovascular 
disease) should be given protection for the stomach when prescribed NSAIDs. NSAIDs and PPIs (Section 1.3.5) are often used 
together for these at risk patients.
 
Cox IIs (cyclo-oxygenase II selective inhibitors)
 
The MHRA has issued the following general advice concerning all selective COX-2 inhibitors (Feb-05):
          >     Patients with established ischaemic heart disease, cerebrovascular disease or peripheral arterial disease should be
                 switched to alternative treatment 
          >     For all patients the balance of gastrointestinal and cardiovascular risk should be considered before prescribing a 
                 COX-2 inhibitor, particularly for those with risk factors for heart disease and those taking low dose aspirin, for whom
                 gastrointestinal benefit has not been clearly demonstrated.
          >     The lowest effective dose of COX-2 inhibitor should be used for the shortest necessary period.  Periodic re-evaluation 
                 is recommended, especially for osteoarthritis patients who may only require intermittent treatment.
          >     Gastro-protective agents should be considered for patients switched to non-selective NSAIDs.
 
GREEN         Celecoxib  
                    capsules 100mg, 200mg  
GREEN        Meloxicam 
                    tablets 7.5mg, 15mg         
AMBER      Etoricoxib (Rheumatology initiation only) 
                   tablets 60mg, 90mg, 120mg    
 
Osteoarthritis - NICE Clinical Guideline 177 February 2014 
Treatment and management 
 
Core treatment: 
There are three core interventions which should be considered for every person with osteoarthritis:  
          >     access to appropriate patient information sources,
          >     activity and exercise,
          >     interventions to achieve weight loss if person is overweight or obese. 
 
If further treatment is required then adjunctive treatments should be considered; 
 
          >     Paracetamol (regular dosing may be required). AND/OR
          >     topical non steroidal anti-inflammatory drugs (NSAIDs) or topical capsaicin for knee or hand osteoarthritis
 
If above agent/s are ineffective or insufficient then consider;
          >     Substitution or addition of an oral NSAID or COX-2 inhibitor (but NOT eterocoxib) OR
          >     Opioid analgesics  
 
Consider intra-articular corticosteroid injections if pain is moderate to severe.
 
Treatment with oral NSAIDs/COX-2 inhibitors:
All oral NSAIDs/COX-2 inhibitors have similar analgesic effects but vary in their gastrointestinal, liver and cardio-renal toxicity. This 
should be taken into account when choosing the drug and dose for an individual patient.
 
Treatment with oral NSAIDs/COX-2 inhibitors:
          >     Prescribe the lowest effective dose for the shortest possible period of time,
          >     ALWAYS co-prescribe a proton pump inhibitor (PPI) - choose one with the lowest cost.
          >     Assess patient risk factors for gastrointestinal, liver and cardio-renal toxicity,
          >     Consider ongoing monitoring of patient risk factors,
          >     Use an alternative analgesic if patient is taking low-dose aspirin.
 
Treatment with opioids: 
          >     Consider the risks and benefits particularly in elderly people.
          >     Adverse effects: constipation, nausea, itchiness, drowsiness and confusion
 
Non-pharmacological: 
          >     Application of heat or cold to the site of pain.
          >     Transcutaneous electrical nerve stimulation (TENS).
          >     Manipulation and stretching, particularly for hip osteoarthritis.
          >     Assessment for bracing/joint supports/insoles for people with biomechanical joint pain or instability.
          >     Assistive devices (for example, walking sticks and tap turners) for people with specific problems with daily activities. 
                 Expert advice may be required.
 
Treatments not recommended 
          >     Rubefacients
          >     intra-articular hyaluronan injections
          >     electro-acupuncture
          >     chondroitin or glucosamine products