Are topical Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) safer and more effective than oral NSAIDs?

From the Guidelines

Topical NSAIDs are generally safer than oral NSAIDs, while oral NSAIDs tend to be more effective for widespread or severe pain. The most recent and highest quality study, published in 2021 1, found that topical diclofenac was superior to placebo and equivalent to oral diclofenac at reducing pain associated with OA of the knee. This study also reported that treatment with topical NSAIDs was associated with markedly fewer gastrointestinal adverse events but had substantially more local adverse events than with oral NSAIDs.

Key Considerations

• Topical NSAIDs like diclofenac gel (Voltaren, 1% applied 4 times daily) deliver medication directly to the affected area with minimal systemic absorption, resulting in fewer gastrointestinal, cardiovascular, and renal side effects compared to oral options 2.
• Oral NSAIDs such as ibuprofen (400-800mg three times daily), naproxen (500mg twice daily), or celecoxib (200mg daily) provide more widespread pain relief and are better for conditions affecting multiple joints or when inflammation is a major component.
• The choice between topical and oral NSAIDs should consider the location and severity of pain, patient's age, medical history, and risk factors for NSAID-related complications.

Patient-Specific Factors

• For localized pain in a single joint or area, especially in high-risk patients, topical NSAIDs offer a favorable safety profile 1.
• For more severe, widespread, or deep-seated pain, oral NSAIDs may be necessary despite their higher risk of systemic side effects.

Safety Profile

• Topical NSAIDs have a lower risk of gastrointestinal, cardiovascular, and renal side effects compared to oral NSAIDs 2, 1.
• However, topical NSAIDs may have more local adverse events, such as skin irritation or allergic reactions.

From the FDA Drug Label

5.17 Oral Nonsteroidal Anti-Inflammatory Drugs Concomitant use of oral NSAIDs with diclofenac sodium topical solution 1. 5% resulted in a higher rate of rectal hemorrhage, more frequent abnormal creatinine, urea and hemoglobin. The concomitant use of diclofenac with other NSAIDs or salicylates (e.g., diflunisal, salsalate) increases the risk of GI toxicity, with little or no increase in efficacy [ seeWarnings and Precautions ( 5. 2) ].

5. 1 Cardiovascular Thrombotic Events Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, including myocardial infarction (MI), and stroke, which can be fatal

Topical NSAIDs may be safer than oral NSAIDs in terms of gastrointestinal toxicity and cardiovascular risk, as the topical formulation has a lower systemic absorption. However, the effectiveness of topical NSAIDs compared to oral NSAIDs is not directly addressed in the provided drug labels.

• The labels do mention that concomitant use of oral NSAIDs with topical diclofenac increases the risk of GI toxicity and cardiovascular events.
• The labels also warn about the risks of cardiovascular thrombotic events associated with NSAID use, but do not provide a direct comparison between topical and oral formulations.
• It is recommended to use the lowest effective dose for the shortest duration possible to minimize the potential risk of adverse events 3.
• The decision to use topical or oral NSAIDs should be based on individual patient needs and medical history, and patients should be monitored for signs of adverse events.

From the Research

Comparison of Topical and Oral NSAIDs

• Topical NSAIDs have been shown to be a safer alternative to oral NSAIDs, with minimal systemic absorption and risk of related adverse events 4, 5.
• The efficacy of topical NSAIDs is similar to that of oral NSAIDs, making them a viable option for treating acute, localized, soft tissue injuries or painful conditions 5.
• Topical NSAIDs have a more favorable safety profile than oral NSAIDs due to the low serum concentrations achieved with topical NSAID formulations 5.

Safety and Efficacy of Topical NSAIDs

• Topical NSAIDs have been used for many years in Europe, with extensive post-marketing data available for some of the agents 4.
• Three topical NSAID formulations have recently been approved for use in the United States: the diclofenac epolamine topical patch 1.3%, diclofenac sodium 1% gel, and diclofenac sodium topical solution 1.5% 4.
• Recent studies suggest that topical diclofenac preparations are effective for osteoarthritis pain, with similar efficacy to oral NSAID formulations 5.

Risks and Benefits of Oral NSAIDs

• Oral NSAIDs have been associated with rare serious gastrointestinal side effects, as well as adverse cardiovascular effects 6, 7.
• Proton pump inhibitors (PPIs) can be used to reduce the risk of NSAID-induced gastrointestinal adverse events, but may also potentiate the GI risks associated with NSAIDs 7, 8.
• The concomitant prescription of PPIs and NSAIDs, such as diclofenac, can decrease the hospitalization risk due to peptic ulcer significantly 8.