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Topical or Oral NSAIDs - Which Is Preferred?

Adverse Events Associated with Topical or Oral NSAIDs May Help You Decide


Updated August 18, 2008

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most popular and most commonly prescribed medications for arthritis. NSAIDs can be taken orally in the form of tablets or capsules. NSAIDs are also available in a topical formulation.

How Do Topical NSAIDs Work?

Topical NSAIDs, such as topical ibuprofen or Voltaren gel, are applied to the skin over a painful joint. There are certain advantages linked to topical NSAIDs including:

  • enhanced drug delivery to affected tissues
  • reduced incidence of systemic adverse effects (e.g., peptic ulcer disease and gastrointestinal bleeding)

Topical NSAIDs penetrate slowly, delivering small amounts in to the systemic circulation. Topical application leads to relatively high NSAID concentrations in the dermis (the layer of skin beneath the epidermis that consists of connective tissue) compared with oral NSAIDs. Concentrations achieved in the muscle tissue below the site of application vary, but it's at least equivalent to what's achieved with oral administration of NSAIDs.

Topical NSAIDs do reach the synovial fluid, but how much and the exact mechanism have yet to be determined. Actually, with regard to the absorption of topical NSAIDs, individual differences in skin may account for certain differences.

Generally speaking, it's difficult to determine which is better — topical or oral NSAIDs — because it has been demonstrated that in clinical trials there is a very high placebo rate.

How Do Oral NSAIDs Work?

Oral (taken by mouth) NSAIDs work by inhibiting cyclooxygenase (COX), an enzyme which catalyzes arachidonic acid to prostaglandins and leukotrienes. Arachidonic acid is released from membrane phospholipids in response to inflammatory stimuli. Prostaglandins establish the inflammatory response. NSAIDs interfere with the production of prostaglandins by inhibiting cyclooxygenase.

The Differences in Adverse Events Between Oral and Topical NSAIDs

Topical NSAIDs have a better safety profile than oral NSAIDs. Adverse effects secondary to topical NSAID use occurs in about 10 to 15% of patients and are primarily cutaneous (rash and pruritus where the topical NSAID was applied). Gastrointestinal adverse drug reactions are rare with topical NSAIDs, compared with a 15% incidence reported for oral NSAIDs.

How Patients Choose Between Oral and Topical NSAIDs

From two reports published in the British Medical Journal (BMJ), it became clear that the decision over which NSAID formulation, oral or topical, to use is typically based on:

  • patient perception of the risk of adverse effects
  • the presence of another illness
  • pain level
  • advice received
  • practicality (cost and ease of use)

In the BMJ, researchers concluded that "topical NSAIDs are a viable, safe alternative to oral NSAIDs for the treatment of knee osteoarthritis, even if a placebo effect explains most of the value of these topical agents." As always, discuss your options with your doctor.


Oral versus topical NSAIDs in rheumatic diseases: a comparison. Drugs. 2000 Sep;60(3):555-74. Heyneman CA et al.

Oral vs. topical NSAID for OA pain - how and why people choose treatments. December 5, 2007. UKMiCentral. NHS.

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