NSAIDS Comparison : Diclofenac, Ibuprofen & Mefenamic Acid

General Principle

• Effective for treatment of acute and chronic painful and inflammatory conditions. 
• Short-to-moderate-acting NSAIDs (eg, naproxen, ibuprofen) are preferred for most patients. Dose- and age-related risk of gastropathy. May cause or worsen renal impairment. 
• Avoid NSAIDs in patients with renal insufficiency (CrCl<60 mL/minute), GI bleeding, platelet dysfunction, reduced cardiac output, difficult-to-control hypertension, hypovolemia, hyponatremia, aspirin-sensitive asthma, or cirrhosis.
• Use with caution or avoid in patients receiving comedication with anticoagulants, systemic glucocorticoids, lithium, loop diuretics, and other interacting drugs.
• Though some older adults may benefit from a brief course of NSAIDs at the lowest effective dose, use in most older adults should be avoided. 

Efficacy 

• Based on Dean, 2011 For short term pain relief (less than 6 months), all NSAIDs have a similar effect on reducing pain in adults with chronic pain from either osteoarthritis, rheumatoid arthritis, soft-tissue pain, back pain, or ankylosing spondylitis. There is little difference in the analgesic efficacy between the different types of NSAIDs.
• In a review by Ong 2007, recent evidence has shown that individual NSAIDs do differ in their analgesic efficacy and the Oxford League Table has been suggested as a good tool for assessing the relative efficacy of analgesics.

Analgesic	Number of patients in comparison	Patient with at least 50% pain relief	NNT	Lower confidence interval	Higher confidence interval
Ibuprofen 800mg	76	100	1.6	1.3	2.2
Diclofenac 100mg	411	67	1.9	1.6	2.2
Diclofenac 50mg	738	63	2.3	1.7	2.7
Ibuprofen 600mg	203	79	2.4	1.5	4.9
Ibuprofen 400mg	4703	56	2.4	2.3	2.6
Diclofenac 25mg	204	54	2.8	2.1	4.3
Paracetamol 500mg	561	61	3.5	2.2	13.3
Paracetamol 1500mg	138	65	3.7	2.3	9.5
Paracetamol 1000mg	2759	46	3.8	3.4	4.4
Placebo	>10000	18	N/A	N/A	N/A

Adapted from Oxford League Table 

• The Oxford pain group has constructed the Oxford League Table for analgesics in acute pain by giving each analgesic a number to grade its efficacy The efficacy of analgesics is expressed as the number-needed-to-treat (NNT), the number of patients who need to receive the active drug for one to achieve at least 50% relief of pain compared with placebo over a 4 to 6 hour treatment period. The most effective drugs would have a low NNT of approximately 2.
• Limitation of Oxford League

1. An assumption of the Oxford League Table is that different pain models are comparable, and that the benefit and harm can be extrapolated from one model to another.
2. Small size of some trials used to combine the data.For instance, trials involving 2800 patients were used to combine the data on the league table concerning acetaminophen with an NNT of 3.8.  However, for ibuprofen 800 mg, which is at the top of the league table with an impressive NNT of 1.6 and with 100% of patients achieving at least 50% pain relief, only 76 patients were ever involved in the comparative trials.

• Such disparity in study size necessitates careful interpretation of results.

Safety Comparison 

Dosing & Other Properties 

Pharmacokinetic Parameters Comparison 

	Onset of Action	Duration	Half Life	Time to Peak	Metabolism	Excretion
Diclofenac Sodium	10 mins	8 hours	~2 hours	~1 hour	Hepatic	Urine (~65%), feces (~35%)
Ibuprofen	30-60 mins	6-8 hours	~2 hours	1-2 hours	Hepatic	Urine & some feces
Mefenamic Acid	Within 2 hours	Up to 8 hours	~2 hours	2-4 hours	Hepatic	Urine (~52%), feces (~20%)

Reference : 

1. http://www.who.int/occupational_health/activities/5injvsora.pdf
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1855338/
3. http://thescipub.com/PDF/amjsp.2012.115.123.pdf
4. http://www.ti.ubc.ca/wordpress/wp-content/uploads/2010/08/39.pdf
5. Overview review: Comparative efficacy of oral ibuprofen and paracetamol (acetaminophen) across acute and chronic pain conditions R.A. Moore1 , S. Derry1 , P.J. Wiffen1 , S. Straube2 , D.J. Aldington3 http://onlinelibrary.wiley.com/doi/10.1002/ejp.649/pdf
6. http://helioscomp.com/docs/default-source/White-Paper/phm14-15241_nsaids-white-paper-final.pdf?sfvrsn=
7. https://www.ncbi.nlm.nih.gov/books/NBK45590/
8. http://www.icm.tn.gov.in/drug%20formulary/ANALGESICS,%20ANTIPYRETICS%20&%20ANTI%20INFLAMMATORY%20DRUGS.htm
9. Lexicomp
10. Uptodate