How Pennsaid Topical Solution Helps Knee Osteoarthritis

Pennsaid is a topical NSAID solution that is FDA approved for treatment of pain and symptoms associated with knee osteoarthritis. The generic name for Pennsaid is diclofenac sodium. Diclofenac is also available by other brand names as a pill, a patch, and a cream.

A woman putting ointment on her knee

Astrid860 / Getty Images

How Does Pennsaid Work?

All non-steroidal anti-inflammatory drugs (NSAIDs) work by a similar mechanism. They inhibit cyclooxygenase, an enzyme responsible for the production of prostaglandins, which are chemical messengers key to the inflammatory cascade. By inhibiting that enzyme, NSAIDs lead to decreased levels of prostaglandins and thus less inflammation.

With topical NSAIDs, the local application of the drug will lead to a decrease in inflammation, and an associated decrease in pain at the site of application. Localized treatment may be safer and more tolerable compared to oral NSAIDs.

Because it is applied topically, the drug will not reach high blood concentrations, so systemic side effects, such as stomach ulcers, are less likely and less severe than they are with oral NSAIDs. In fact, studies have shown that with topical application of NSAIDs, the systemic levels of the drug are substantially lower than they are with oral forms.

Adverse Effects

The most common side effect associated with Pennsaid is mild dryness or irritation where it is applied.

Besides mediating inflammation, prostaglandins are also instrumental in other functions of the body, and thus NSAIDs can have side effects. Notably, prostaglandins are key in the production of the mucous membrane of the stomach, which is important in protecting the stomach lining from acid. Taking NSAIDs can result In impairment of this protective barrier and can lead to stomach irritation and ulcers.

The use of topical NSAIDs in the treatment of knee osteoarthritis offers potential significant gastrointestinal safety benefits for certain patients. The potential for adverse events such as ulcers, gastrointestinal bleeding, and cardiovascular risks still exist, but are lower compared to the pill form of these drugs.

Does It Work?

A randomized clinical placebo-controlled trial examined the side effects of this treatment after the efficacy of diclofenac sodium topical solution was established as superior to placebo and comparable with oral NSAIDs in the management of OA. The researchers concluded that the side effects of the gel were tolerable and less severe than the side effects of the oral treatments.

According to the American College of Rheumatology (ACR) guidelines, topical NSAIDs are recommended as first-line treatment for hand and knee OA.

4 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Jones CA, Hoehler FK, Frangione V, Ledesma G, Wisman PP Jr, Jones C. Safety and efficacy of the FLECTOR (Diclofenac Epolamine) topical system in children with minor soft tissue injuries: A phase IV non-randomized clinical trial. Clin Drug Investig. 2022 Jan;42(1):43-51. doi:10.1007/s40261-021-01101-x

  2. Food and Drug Administration. Pennsaid label.

  3. Roth SH, Fuller P. Diclofenac sodium topical solution 1.5% w/w with dimethyl sulfoxide compared with placebo for the treatment of osteoarthritis: pooled safety results. Postgrad Med. 2011 Nov;123(6):180-8. doi:10.3810/pgm.2011.11.2507

  4. Kolasinski SL, Neogi T, Hochberg MC, Oatis C, Guyatt G, Block J, Callahan L, Copenhaver C, Dodge C, Felson D, Gellar K, Harvey WF, Hawker G, Herzig E, Kwoh CK, Nelson AE, Samuels J, Scanzello C, White D, Wise B, Altman RD, DiRenzo D, Fontanarosa J, Giradi G, Ishimori M, Misra D, Shah AA, Shmagel AK, Thoma LM, Turgunbaev M, Turner AS, Reston J. 2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Rheumatol. 2020 Feb;72(2):220-233. doi:10.1002/art.41142

Additional Reading
  • Cochrane Review of Topical NSAIDs.

  • FDA Approves Pennsaid.

  • Pennsaid. NUVO.

By Carol Eustice
Carol Eustice is a writer who covers arthritis and chronic illness. She is the author of "The Everything Health Guide to Arthritis."