Diclofenac (Voltaren®) versus Naproxen (Aleve®)

Based on "Essential Pain Pharmacology"
written by Howard S. Smith, MD; Marco Pappagallo, MD

Difference between Diclofenac and Naproxen

Brand names Voltaren®, Cataflam® Aleve®, Naprosyn®
Formulations • Tablets
• Capsules
• Topical gel
• Transdermal patch
• Ophthalmic solution
• Powder for oral solution
• Injection
• Tablets
• Gelcaps
• Oral suspension
Drug class Non-steroidal anti-inflammatory drugs (NSAIDs)
Phenylacetic acid derivative Propionic acid derivative
Legal status Non-controlled substance
Prescription Prescription,
Abuse potential No
FDA-approved Indications • Rheumatoid arthritis
• Osteoarthritis
• Ankylosing spondylitis
• Primary dysmenorrhea
• Mild to moderate pain
• Migraine attacks • Tendonitis
• Bursitis
• Gout
Off-label uses • Multimodal analgesic regimen
• Dental surgical procedures
• Acute pain in children10
• Biliary colic12
Mechanism of action • Inhibit prostaglandin synthesis via non-selective inhibition of COX-1 and 2 COX-2 resulting in reduced formation of prostaglandins, thromboxane, and prostacyclin.
• Diclofenac has more selectivity for COX-2 than naproxen.
• Diclofenac appears to inhibit the lipoxygenase pathways, reducing inflammation by decreasing production of leukotrienes.
• Diclofenac also inhibits arachidonic acid release and stimulates its reuptake
• Naproxen
inhibits platelet aggregation and its antiplatelet effect is equal to that of low-dose aspirin11
Therapeutic effects • Analgesic
• Antipyretic (anti-fever)
• Anti-inflammatory
Half-life 1-4 hours
Diclofenac accumulates in synovial fluid, which may explain why
its duration of therapeutic effect is considerably longer than its half-life1
14 hours
Half-life is longer but variable, and may increase about 2-fold in the elderly because of decline in renal function.
Oral bioavailability 50-60% 95%
Metabolism, Elimination Diclofenac undergoes first-pass or presystemic elimination. Diclofenac is metabolized in the liver by CYP2C9 to 4-hydroxydiclofenac, the main metabolite, and other hydroxylated forms. After glucuronidation and sulfation, the conjugates are elimination in the urine (65%) and bile (35%). Less than 1% of the drug is excreted unchanged. Naproxen undergoes hepatic metabolism (95%) with 30% of the drug being metabolized to 6-demethylation. Unchanged naproxen and most of its metabolites are excreted as the glucuronide or other conjugate. After liver conjugation, 95% of the drug is eliminated by the kidneys.
Contraindications • Hypersensitivity to naproxen, diclofenac, or other NSAIDs
• Use during the peri-operative period in the setting of coronary artery bypass graft (CABG) surgery
• Third trimester of pregnancy
• Active gastric/duodenal/peptic ulcer, active GI bleeding or perforation, regional ulcer, gastritis or ulcerative colitis
• Severe hepatic impairment or active liver disease
Side effects • Gastric discomfort, nausea, vomiting, diarrhea, abdominal pain, gastric mucosal damage, flatulence, peptic ulceration
• Dizziness, tinnitus, headache
• Bleeding
• Pruritus, rashes
• Modest elevation of hepatic transaminases occurs in 5-15% of patients.
• Diclofenac elevates risk of cardiovascular adverse effects even at low doses2. Diclofenac is associated with the highest cardiovascular risk among non-selective NSAIDs.
• Diclofenac has a lower risk of GI side effects compared to naproxen.
• Naproxen appears to be risk-neutral with regard to cardiovascular adverse events, even at higher doses2.
Pregnancy category C prior to 30 week s gestation
D starting at 30 weeks gestation
Drug interactions • Concomitant use with potassium-sparing diuretics, ACE inhibitors, angiotensin-II receptor antagonists, or other medications that may cause hyperkalemia may result in increased serum potassium levels.  
Tolerability Diclofenac appears to be better tolerated than naproxen6, 7.
Advantages • Important advantage of diclofenac is that it has an about 10-fold preference to block the COX-2 isoenzyme, which results in lower rate of upset stomach, peptic ulcers, and gastrointestinal bleeding compared with other NSAIDs.
• Diclofenac is a better choice for patients with ulcers.
• Over-the-counter formulations
• Naproxen toxicity is relatively uncommon compared to other NSAIDs.
• Naproxen is a better choice for patients with high cardiovascular risk.


Comparative Efficacy

Osteo-arthrosis of hip or knee
Diclofenac is more effective in relieving pain and stiffness and improving range of joint movements3.

Rheumatoid arthritis
Both naproxen and diclofenac exert similar positive effects on the duration of morning stiffness, bilateral grip strength, and pain4.

Soft-tissue rheumatism
Both medications provide similar therapeutic effect in relieving symptoms of soft-tissue rheumatism, including pain at rest and on movement, swelling, tenderness, limitation of movement5. However, in patients with diseases affecting the shoulder region diclofenac is more effective.

Diclofenac provides more strong analgesic effect in arthritis6.

Sports injuries
Diclofenac produces faster and better analgesia compared to naproxen for acute pain following minor sports injuries8.

Third molar surgery
Diclofenac is better than naproxen for reducing pain and swelling following extraction of mandibular third molars9.

Further reading


  • 1. Altman R, Bosch B, Brune K, Patrignani P, Young C. Advances in NSAID development: evolution of diclofenac products using pharmaceutical technology. Drugs. 2015 May;75(8):859-77. PubMed
  • 2. McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med. 2011 Sep;8(9):e1001098. PubMed
  • 3. Siraux P. Diclofenac for the treatment of osteo-arthrosis: a double-blind comparison with naproxen. J Int Med Res. 1977;5(3):169-74. PubMed
  • 4. Kajander A, Martio J. Diclofenac sodium (Voltaren) and naproxen in the treatment of rheumatoid arthritis: a comparative double-blind study. Scand J Rheumatol Suppl. 1978;(22):57-62. PubMed
  • 5. Valtonen EJ. A comparative short-term trial with Voltaren and naproxen in soft-tissue rheumatism. Scand J Rheumatol Suppl. 1978;(22):69-73. PubMed
  • 6. Siegmeth W, Placheta P. Long-term comparative study: diclofenac (voltaren) and naproxen (proxen) in arthritis. Schweiz Med Wochenschr. 1978 Mar 4;108(9):349-53. PubMed
  • 7. Bach GL. Comparative clinical trials with diclofenac sodium and naproxen in rheumatic conditions. Rheumatol Rehabil. 1979;Suppl 2:69-74.
  • 8. Colombo G, Giombini A, Pamich T, Peruzzi E, Pisati R. Diclofenac dispersible provides superior analgesia with faster onset of action compared to naproxen granular in patients with acute, painful, minor sports injuries.
  • 9. Akbulut N, Ustuner E, Atakan C, Colok G. Comparison of the effect of naproxen, etodolac and diclofenac on postoperative sequels following third molar surgery: a randomised, double-blind, crossover study. Med Oral Patol Oral Cir Bucal. 2014 Mar 1;19(2):e149-56. PubMed
  • 10. Standing JF, Savage I, Pritchard D, Waddington M. Diclofenac for acute pain in children. Cochrane Database Syst Rev. 2009 Oct 7 PubMed
  • 11. Schiff M, Hochberg MC, Oldenhof J, Brune K. Platelet inhibitory effects of OTC doses of naproxen compared with prescription dose naproxen and low-dose aspirin. Curr Med Res Opin. 2009 Oct;25(10):2471-7. PubMed
  • 12. Akriviadis EA, Hatzigavriel M, Kapnias D, et al. Treatment of biliary colic with diclofenac: a randomized, double-blind, placebo-controlled study. Gastroenterology. 1997 Jul;113(1):225-31.

Published: February 14, 2017
Last updated: April 04, 2017


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