Better Options for Patients: Compounding a Safer Topical NSAID Allows for Less Risky Pain Relief

Better Options for Patients: Compounding a Safer Topical NSAID Allows for Less Risky Pain Relief

i-briefcaseMolly is 54, a Type 2 diabetic and suffers from debilitating peripheral diabetic neuropathy and sciatic nerve pain. She also experiences ulcers from time to time due to a stressful job and home life. Most pharmacists wouldn’t hesitate before recommending a non-steroidal anti-inflammatory (NSAID) for treatment of her PDN and nerve pain, without realizing that while an NSAID would likely give Molly relief from her neuropathy, it could also put her at severe risk of severe bleeding and other complications.

What’s a pharmacist to do when one of the most common pain drugs begins to show signs of being more and more risky for her patients? NSAIDs are one of the most common drugs prescribed for pain related to a number of different conditions, but growing concern over the safety of oral NSAIDs means it might be time for the pharmaceutical industry to find a safer alternative delivery method that can still provide strong pain relief for suffering patients.

Compounding pharmacists can lead the way with topical NSAID solutions. Oral NSAIDs are responsible for roughly one-fourth of all worldwide adverse drug reaction reports. As pharmacists know well, traditional delivery oral NSAIDs put patients at risk of systemic adverse effects including gastroduodenal damage and ulceration.1

A topical NSAID, by contrast, is not absorbed in the same manner and thus significantly reduces the risk of damage to the stomach and gastrointestinal area. This “targeted peripheral therapy” has proven effective in multiple clinical settings, and topical NSAIDs have been found to be equal to oral treatment in efficacy in controlled trials as well.2

Why Traditional NSAIDs Can Create a Dangerous Situation for Patients

The pathophysiology of oral NSAID-related gastrointestinal complications has been mostly attributed to the way the drug inhibits cyclooxygenase (COX). Most NSAIDs inhibit both COX-1 and COX-2 equally, resulting in a deficiency of the active lipid prostaglandin, a compound with a key role to play in protecting and renewing the stomach lining.3

Oral NSAID-induced prostaglandin deficiency can result in a host of secondary effects related to the stomach, such as ulcers and other erosions. At its most severe, however, a deficit of prostaglandin can result in severe adverse effects,  including:

  • acute renal insufficiency
  • NSAID gastropathy,
  • severe bleeding
  • fluid retention
  • nephrotic syndrome4

How a Compounded Topical NSAID Provides Pain Relief with Fewer Risks

Conventional wisdom connects most of the adverse effects of NSAIDs to the inhibition of COX-1, meaning that most research focuses on improving NSAIDs by reducing or eliminating this inhibition and allowing the production of prostaglandin, while simultaneously inhibiting COX-2 to actual accomplish pain relief in the body. There is some experimental data from animal trials that shows that simultaneous COX-1 and COX-2 inhibition is required for gastric ulceration, potentially challenging the conclusion that only COX-1 must be uninhibited. For most pharmacists’ purposes and for human patients, however, finding a way to only inhibit COX-2 reduces patient risk of GI damage.

A topical NSAID application functions in exactly this way, inhibiting only COX-2 and not COX-1, allowing the uninterrupted production of prostaglandin to protect the stomach lining and reduce instances of NSAID-induced ruptures and other serious issues. Using a topical NSAID can reduce the risk of overall systemic adverse effects for a number of conditions, including musculoskeletal diseases, rheumatic diseases, and even plantar fascia or other podiatry-related pain.

For musculoskeletal diseases, a review of clinical studies found that use of a topical NSAID provided “good levels of pain relief in acute conditions,” which the study categorized as sprains, strains and overuse injuries. Although that study did not find enough data to compare topical NSAIDs with their direct oral counterparts, the instances of withdrawals from the trials due to adverse effects were low.5

A review of trials related to the use of a topical NSAID for treating rheumatic diseases came to similar conclusions about suggested equivalent efficacy and lower rates of adverse absorption. The diseases examined included bursitis, tendinitis, osteoarthritis and epicondylitis, and reported an approximately 10 percent rate of secondary adverse effects versus a 15 percent incidence reported for oral NSAIDs.

Podiatrists have also reported qualitative success with the use of topical NSAIDs for conditions such as plantar fascia pain and Achilles tendonitis. Topical NSAIDs compounded for these applications typically had 5 percent or less of the serum levels of equivalent systemic deliveries for the same treatment, lowering incidences of adverse reactions and also of adverse drug interactions for patients taking multiple medications. Podiatrists reported that the compounded topical medications allowed for combining multiple agents with multiple action mechanisms, greatly increasing the options for providing patient pain relief.6

The Role of the Compounding Pharmacist in the Growth of Topical NSAIDs

As the pharmacist becomes more integrated into a patient’s health care team and takes on more treatment responsibilities, they can ensure that patients or prescribing physicians are fully aware of all the options for pain relief, including using a topical NSAID where topical medication might be more appropriate.

Targeted peripheral therapies have gained acceptance more quickly in Europe than in the U.S., where the use of oral medications still far outpaces topicals, despite the increased stomach and gastrointestinal risks from traditional NSAID delivery methods. It is possible to see some progress in the U.S., however, especially the way many major health associations like the American Heart Association have recommended that oral NSAIDs be prescribed more sparingly within the last five years.7

Compounding pharmacists can make sure that topical NSAIDs enter the discussion as alternatives to risky oral NSAIDs. As with any drug class, it’s important to explore whether compounding can play a role in not only relieving patient pain, but promoting patient well-being.

Pharmaceutica North America is a leading provider of high-quality compounding kits and active pharmaceutical ingredients for compounding pharmacies and other health care organizations, including compounds such as diclofenac and ketoprofen for use in topical NSAIDs. Contact us to learn more about our products.

Show 7 footnotes

  1. “The pathophysiology of non-steroidal anti-inflammatory drug (NSAID)-induced mucosal injuries in stomach and small intestine,” March 2011,
  2. “Topical NSAIDs for acute pain: a meta-analysis,” May 17, 2004,
  3. “Prostaglandins and Inflammation,” May 1, 2012,
  4. “Oral versus Topical NSAIDs in Rheumatic Diseases,” Sept. 2000,
  5. “Topical non-steroidal anti-inflammatory drugs for acute musculoskeletal pain in adults,” Feb. 4, 2015,
  6. “How Topical Compounding Has Worked for My Patients,” Jan. 15, 2013,
  7. “Topical NSAIDs: Is the Skin the New Stomach?” July 2008,

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