Is topical Non-Steroidal Anti-Inflammatory Drug (NSAID) safe for patients with impaired renal function?

From the Guidelines

Topical NSAIDs are generally considered safe for patients with impaired renal function, as they result in minimal systemic absorption and limited risk of worsening renal function. Unlike oral NSAIDs, which should be avoided in patients with kidney disease, topical formulations typically have less than 5-10% of the equivalent oral dose absorbed systemically 1. This limited systemic exposure significantly reduces the risk of worsening renal function. Common topical NSAIDs include diclofenac (Voltaren, Pennsaid), ketoprofen, and ibuprofen gels or patches. These medications should be applied as directed on the package, usually 2-4 times daily to the affected area, using only the recommended amount. It's essential to avoid applying topical NSAIDs to broken or irritated skin, which could increase absorption. While generally safe, patients with severe renal impairment (GFR <30 ml/min) should still use these products with caution and under medical supervision, as recommended by the revised Beers criteria for potentially inappropriate medication use in older adults 1. Patients should monitor for any unusual symptoms and report them to their healthcare provider. The safety of topical NSAIDs in renal impairment stems from their localized action at the site of pain and inflammation without significantly affecting renal prostaglandin production, which is the mechanism by which oral NSAIDs can impair kidney function.

Some key considerations for patients with renal impairment include:

• Avoiding the use of other nephrotoxic agents, such as oral NSAIDs, trimethoprim, and certain diuretics 1
• Monitoring blood chemistry regularly, especially in patients with severe renal impairment 1
• Using topical NSAIDs with caution and under medical supervision in patients with GFR <30 ml/min 1
• Educating patients to report any unusual symptoms to their healthcare provider 1

Overall, the use of topical NSAIDs in patients with impaired renal function is considered safe, as long as they are used with caution and under medical supervision, especially in patients with severe renal impairment.

From the FDA Drug Label

Patients with significantly impaired renal function should be closely monitored, and a reduction of dosage should be anticipated to avoid accumulation of ketoprofen and/or its metabolites ACE Inhibitors and ARBs:Concomitant use with diclofenac sodium topical solution in elderly, volume depleted, or those with renal impairment may result in deterioration of renal function. In such high-risk patients, monitor for signs of worsening renal function

Topical NSAID Safety in Renal Failure:

• The use of topical NSAIDs in patients with impaired renal function requires caution.
• Monitoring of renal function is recommended when using topical NSAIDs in patients with renal impairment.
• Dose reduction may be necessary to avoid accumulation of the drug and/or its metabolites.
• Concomitant use of certain medications, such as ACE inhibitors and ARBs, may increase the risk of renal dysfunction in patients with impaired renal function 2 3. Key Considerations:
• Patients with renal impairment are at higher risk of renal toxicity when using NSAIDs.
• Topical NSAIDs may still be absorbed systemically and affect renal function.
• Close monitoring and dose adjustment are necessary to minimize the risk of adverse effects.

From the Research

Safety of Topical NSAIDs in Patients with Renal Failure

• The safety of topical Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in patients with renal failure is a topic of interest, with some studies suggesting that they may be a safer alternative to systemic NSAIDs 4.
• A study published in 2021 found that topical NSAIDs were associated with a reduced incidence of acute kidney injury and/or hyperkalemia in older adults with co-morbid conditions, compared to short-course systemic NSAIDs 4.
• However, another study published in 2020 noted that NSAID use has been associated with acute kidney injury, progressive loss of glomerular filtration rate in CKD, electrolyte derangements, and hypervolemia with worsening of heart failure and hypertension 5.
• A review of the current literature on the use of NSAIDs in end-stage kidney disease patients suggested that the evidence directly examining the impact of NSAIDs on long-term outcomes in ESKD is limited, and further study is warranted 6.

Comparison of Topical and Systemic NSAIDs

• A study published in 2021 found that both short-course systemic NSAIDs and topical NSAIDs were independently associated with an increased risk of acute adverse renal events in older adults, but topical NSAIDs had a reduced odds of 30-day incident acute kidney injury and/or hyperkalemia in patients with diabetes mellitus, chronic kidney disease, and cardiovascular disease 4.
• Another study published in 2007 found that NSAIDs caused a clinically unimportant transient reduction in renal function in the early postoperative period in patients with normal preoperative renal function, but did not find any significant difference in serum creatinine between patients receiving different types of NSAIDs 7.

Renal Safety of NSAIDs

• The renal safety of NSAIDs is a concern, particularly in patients with pre-existing renal disease 5, 6.
• A study published in 2025 found that NSAIDs may reduce pain in adult patients with renal colic compared to placebo, but the evidence is uncertain regarding the potential harms of NSAIDs 8.
• The use of NSAIDs in patients with renal failure should be cautious and individualized, taking into account the patient's underlying renal function and other comorbid conditions 5, 6.