NSAID Therapy

“Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of pain associated with a variety of indications, including arthritic conditions, but their usefulness is often limited by dose-dependent adverse events such as gastrointestinal disturbances, cardiovascular events, and renal toxicity. The risk of such effects could be reduced by the use of topical formulations, which offer the potential to deliver analgesic concentrations locally, at the site of inflammation, while minimizing systemic concentrations… Meta-analyses have confirmed the efficacy and safety of these [TOPICAL] preparations. However, it is important to recognize that pharmacokinetics [and] absorption from topical formulations can vary markedly, even between different formulations of the same drug, depending on the agent, the underlying disorder, and the site of application. It is therefore essential to consider the patient, the drug, and the drug delivery mechanism when selecting a topical NSAID preparation.”

Am J Ther. 2015 Sep-Oct;22(5):388-407
Topical Nonsteroidal Anti-Inflammatory Drugs: The Importance of Drug, Delivery, and Therapeutic Outcome.

Click here to access the PubMed abstract of this article.

Topical Therapies in the Management of Chronic Pain

Chronic pain, whether localized or generalized, is a widespread, often debilitating condition affecting > 25% of adults. Topical therapies offer advantages over systemically administered medications, including the requirement of a lower total systemic daily dose for patients to achieve pain relief, site-specific drug delivery, and avoidance of first-pass metabolism, major drug interactions, and systemic side effects. Topical NSAIDs have been shown to have a lower incidence of gastrointestinal complaints than oral formulations. In patients with neuropathic pain, topical formulations have been shown to be useful in the treatment of postherpetic neuralgia and diabetic peripheral neuropathic pain, and in relieving patient pain due to complex regional pain syndrome. Data suggest that topical therapies may offer a well-tolerated alternative to systemic therapies in the treatment of patients with chronic, localized musculoskeletal and neuropathic pain.

Postgrad Med. 2013 Jul;125(4 Suppl 1):25-33.
Topical therapies in the management of chronic pain.
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Comparison of Analgesic Activities of Compounded Topical Creams and Voltaren® Gel in Chronic Non-cancer Pain

Pharmacologic treatment of chronic pain is challenging. Oral therapy may require multiple medications; each has side effects, dose limitations, and limited efficacy. Compounded topical formulations have evolved as potential treatment options. The objective of a study was to evaluate the efficacy of 2 compounded topical creams, “Cream I” and “Cream II,” in patients with chronic extremity, joint, musculoskeletal, neuropathic, or other chronic pain conditions and compare their efficacy with Voltaren® gel. The primary efficacy outcome was the change in visual numeric pain intensity score from pretreatment to posttreatment. Cream I contained flurbiprofen 20%, tramadol 5%, clonidine 0.2%, cyclobenzaprine 4%, and bupivacaine 3%. Cream II contained flurbiprofen 20%, baclofen 2%, clonidine 0.2%, gabapentin 10%, and lidocaine 5%. The Voltaren® gel contained 1% diclofenac sodium. A total of 2177 patients were evaluated, 826 males and 1351 females. During their medical treatment, 1141 patients received Cream I, 527 patients received Cream II, and 509 patients received Voltaren® gel. After treatment, the pain intensity score decreased by 37% with Cream I, by 35% with Cream II, and by 19% with Voltaren® gel. Cream I and Cream II did not differ significantly in efficacy, and both were significantly more effective than Voltaren® gel.

Am J Ther. 2015 Sep-Oct;22(5):342-9.
Retrospective Evaluation on the Analgesic Activities of 2 Compounded Topical Creams and Voltaren® Gel in Chronic Noncancer Pain.
Click here to access the PubMed abstract of this article.

To avoid the risks of COX-2 inhibitors, our pharmacy can compound topically applied NSAIDs such as ibuprofen and ketoprofen. Topical NSAIDs have a safety profile which is superior to oral formulations. Topical NSAID administration offers the advantage of local, enhanced delivery to painful sites with a reduced incidence of systemic adverse effects.

Topical preparations can be customized to contain a combination of medications to meet the specific needs of each patient.

This study concluded that topical NSAIDs, when used for treatment of pain resulting from strains, sprains or sports or overuse-type injuries, can provide good levels of pain relief without the systemic adverse events associated with oral NSAIDs.

Cochrane Database Syst Rev. 2010 Jun 16; 6: CD007402.
Topical NSAIDs for acute pain in adults. .
Click here to access the PubMed abstract of this article.

“Topical non-steroidal anti-inflammatory drugs have a lower incidence of gastrointestinal adverse effects than the same drugs when they are taken orally. The low incidence of systemic adverse effects for topical NSAIDs probably results from the much lower plasma concentration from similar doses applied topically to those administered orally. Topical application of ibuprofen resulted in measurable tissue concentrations in deep tissue compartments, more than enough to inhibit inflammatory enzymes.”

BMJ. 1995 Jul 1;311(6996):22-6
Topical non-steroidal anti-inflammatory drugs and admission to hospital for upper gastrointestinal bleeding and perforation: a record linkage case-control study.
Free full text article available at bmj.com:

This study concludes that topical NSAIDs have not been associated with renal failure.

QJM. 1995 Aug;88(8):551-7
Non-steroidal anti-inflammatory drugs and hospitalization for acute renal failure.
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The following article concludes: “Topical non-steroidal anti-inflammatory drugs are effective in relieving pain in acute and chronic conditions.”

BMJ. 1998 Jan 31;316(7128):333-8
Quantitative systematic review of topically applied non-steroidal anti-inflammatory drugs.
Click here to access the PubMed abstract of this article.

The following article reports “The systemic concentrations of ketoprofen have also been found to be 100 fold lower compared to tissue concentrations below the application site in patients undergoing knee joint surgery. Topically applied ketoprofen thus provides high local concentration below the site of application but lower systemic exposure.”

Pharm Res. 1996 Jan;13(1):168-72
Percutaneous absorption of ketoprofen from different anatomical sites in man.


Sever disease is the most common cause of heel pain in pre-pubertal children. This inflammatory condition is a result of minor repetitive trauma and typically occurs during a growth spurt or at the beginning of a new sport season. A case report described the use of topical ketoprofen 10% gel to relieve pain and inflammation.

Phys Ther. 2006 Mar;86(3):424-33
Ketoprofen gel as an adjunct to physical therapist management of a child with Sever disease.
Click here to access the PubMed abstract of this article.