Diclofenac sodium topical solution (Pennsaid): Nonsteroidal anti-inflammatory topical solution approved for chronic management of knee osteoarthritis

New formulation: Diclofenac sodium topical solution (Pennsaid) was approved on November 5, 2009, to treat the signs and symptoms of osteoarthritis of the knee.

Diclofenac sodium 1.5% w/w topical solution was approved by FDA on November 5, 2009, to treat the signs and symptoms of osteoarthritis of the knee. The active ingredient, diclofenac sodium, is a nonsteroidal anti-inflammatory drug (NSAID). NSAIDs inhibit the enzyme cyclooxygenase, an early component of the arachiodonic acid cascade, causing reduced formation of prostaglandins, thromboxanes, and prostacyclin. This formulation is a solution containing dimethyl sulfoxide, popularly known as DMSO, which acts as a transdermal carrier, delivering the active drug through the skin directly to the painful site.

Efficacy. The efficacy of this topical solution was assessed in 2 double-blind, controlled trials. In Study 1, 154 patients received diclofenac at 40 drops 4 times daily, 155 received topical placebo, and 161 patients received topical vehicle solution directly to the study knee for 12 weeks. Statistically significant clinical improvement from baseline was seen with diclofenac sodium versus placebo and vehicle solutions in the efficacy variables of Western Ontario and McMaster Universities (WOMAC) pain score (-6.0 vs -4.7, -4.7), WOMAC physical function (-15.7 vs -12.3, -12.1), and Patient Overall Health Assessment (-1.0 vs -0.4, -0.6). In Study 2, 164 patients received diclofenac sodium and 162 patients received topical vehicle solution. Similarly strong clinical improvement was seen with use of diclofenac sodium: WOMAC pain score was -5.9 vs -4.4, WOMAC physical function was -15.3 vs -10.3, and Patient Global Assessment was -1.3 vs -1.0.

Safety. Published clinical trials suggest that some systemic side effects seen with oral NSAIDs such as gastrointestinal (GI) bleeding and cardiovascular problems occur less frequently with the topically applied diclofenac sodium solution. However, serious and potentially fatal cardiovascular thrombotic events, myocardial infarction, and stroke may occur with all NSAIDs. GI adverse events include bleeding, ulceration, and perforation of the stomach or intestines. Since these risks may increase with duration of use; the lowest effective dose should be used for the shortest possible duration. For 911 patients in 7 phase 3 controlled trials and 793 patients studied in an open-label study treated with diclofenac topical solution, the most common adverse events were application site skin reactions.