Topical Nonsteroidal Anti-Inflammatory Drugs

  • Sarah Merriam MD
  • René Claxton MD MS

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Background     Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed drugs in the treatment of musculoskeletal pain. Two topical NSAID formulations are commercially available in the United States:  diclofenac sodium gel (Voltaren), diclofenac topical solution (PENNSAID) and diclofenac epolamine topical patch (Flector) (1).  This Fast Fact reviews the pharmacology, clinical efficacy and adverse effects of topical NSAIDs for the treatment of musculoskeletal pain.  

Pharmacology     High plasma concentrations of oral NSAIDs are required to achieve effective tissue concentrations at the site of pain and inflammation.  Topical NSAIDs are believed to deliver adequate local tissue concentrations with minimal systemic absorption.  Plasma concentrations following topical administration of diclofenac sodium gel and the diclofenac epolamine patch are far lower than levels found following oral administration of diclofenac (0.6%-2.2%, and less than 1%, of oral systemic levels, respectively). Time to peak serum concentration for both topical formulations is approximately 10-20 hours (2).

Clinical evidence     NSAIDs are often recommended as first-line treatment for mild-to-moderate musculoskeletal pain (3).  A Cochrane review of the efficacy of topical NSAIDS in the treatment of acute musculoskeletal pain (sprains, strains, contusions) found that compared to placebo, the number needed to treat (NNT) was 4.5 to achieve 50% pain relief over treatment periods of 6-14 days (4). The effectiveness of topical NSAIDs for the treatment of acute low back pain or chronic conditions including chronic back pain is unknown (5).  Several systematic reviews report trials of poor quality with most trial lengths lasting less than 4 weeks and demonstrating inconclusive results (6).  Head-to-head trials comparing oral NSAIDs and their topical equivalents show conflicting results with regards to efficacy and there are insufficient data to perform meta-analysis (4). There are virtually no data about topical NSAID use in patient populations commonly seen in palliative care settings. A literature review in June 2011 identified a single study which showed no benefit from a topical NSAID cream over placebo in the relief of pain related to pressure ulcers (7).

Adverse Effects    Patients taking oral NSAIDs for ≥5 days at least twice annually have a 4.21 relative risk of gastrointestinal events compared to those who do not (8). Conversely, topical NSAIDs have a high margin of safety and have not been associated with acute renal failure or upper GI adverse events. Mild local adverse effects occur at approximately the same rate (6%) in patients treated with topical NSAIDs or topical placebo (5).

Summary     In the treatment of acute musculoskeletal pain, excluding low back pain, topical NSAIDS are more effective than placebo and are associated with fewer adverse events than oral NSAIDs (although this has not been demonstrated in head-to-head trials with oral NSAIDs).  Current data suggest topical NSAIDs are appropriate for patients with a flare of single joint arthritis or acute musculoskeletal injury.  Given the expense of topical NSAIDS (approximately $36 for one 100 gm tube of diclofenac gel and $170 for thirty diclofenac epolamine patches), unclear clinical benefit over prolonged time periods, and unknown efficacy compared to oral preparations, they are not recommended for chronic musculoskeletal pain.  Their use for cancer-related pain syndromes and other indications is entirely empiric.


  1. McPherson ML, Cimino NM. Topical NSAID formulations. Pain Med. 2013; 14(Supp 1):S35-9
  2. Micromedex® Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Reuters (Healthcare) Inc. Updated periodically.
  3. Chou R, Qaseem A, Snow V, et al. Diagnosis and treatment of low back pain: a Joint Clinical Practice Guideline from the American College of Physicians and the American Pain Society. Ann Intern Med. 2007; 7:478-91.
  4. Massey T, Derry S, Moore RA, McQuay HJ. Topical NSAIDs for acute pain in adults. Cochrane Database Syst Rev. 2010; 6: CD007402.
  5. Roelofs PD, Deyo RA, Koes BW, Scholten RJ, van Tulder MW. Nonsteroidal anti-inflammatory drugs for low back pain: An updated Cochrane review. Spine.  2008; 33:1766-74.
  6. Gotzsche P. NSAIDs. Clinical Evidence. 2009; 6(1108).
  7. Prentice WM, Roth LJ, Kelly P. Topical benzydamine cream and the relief of pressure pain. Palliat Med. 2004; 18:520-4.
  8. Singh G, Triadafilopoulus G. Epidemiology of NSAID-induced GI complications. J Rheumatol. 1999; 26:18-24.

Authors’ Affiliation:University of Pittsburgh Medical Center, Pittsburgh, PA.

Version History: Originally published January 2012; Copy-re-edited August 2015 with reference #1 added and incorporated into the text.