Topical diclofenac beats oral formulation in safety, tolerability

April 22, 2011

Topical diclofenac is safer and better tolerated by patients with osteoarthritis of the knee compared with the oral formulation, according to data presented here at annual meeting of the American Academy of Pain Medicine, in National Harbor, Md.

Topical diclofenac (TDiclo) is safer and better tolerated by patients with osteoarthritis (OA) of the knee compared with the oral formulation (ODiclo), according to data presented here at annual meeting of the American Academy of Pain Medicine, in National Harbor, Md. In addition, it is associated with significantly fewer GI-related adverse events.

Data from two 12-week, double-blind, randomized, controlled, multicenter trials comparing the safety and efficacy of TDiclo and ODiclo in 927 patients with knee OA were pooled and analyzed. Only patients who received either TDiclo alone (40 to 50 drops, 3 to 4 times daily) or ODiclo alone (50 mg to 100 mg, 1 to 3 times daily) were included in the analysis.

Significantly more patients treated with ODiclo discontinued the study due to GI-related adverse events (14.5% vs 5.8%, respectively; P<.0001). Overall, serious adverse events occurred in more patients treated with ODiclo compared with TDiclo (8 vs 1, respectively), but there were no statistically significant differences in the overall incidence of serious adverse events. One gastric ulcer hemorrhage was reported in a patient receiving ODiclo. No patient receiving TDiclo experienced a GI-related serious adverse event.

Acute myocardial infarction and coronary artery disease occurred in 3 patients; myocardial infarction in 2 patients treated with ODiclo, and arteriosclerosis in 1 patient treated with TDiclo.

Clinically significant elevations in alanine aminotransferase were reported in more patients receiving ODiclo compared with TDiclo (4.1% vs 1.2%, respectively; P<.01). Liver enzyme levels and creatinine were significantly increased in patients treated with ODiclo (P<.001), and creatinine clearance (P<.0001) and hemoglobin (P<.0001) were significantly increased.

“Overall, these results suggest that due to its increased localized diclofenac absorption with very low systemic levels, TDiclo may yield comparable efficacy to that of ODiclo with significantly less risk of serious GI-related adverse events,” said lead author Sanford H. Roth, MD, medical director, Arizona Research and Education, and adjunct professor, Arthritis Research Lab, Arizona State University, Phoenix, Az.

These studies were supported by Nuvo Research Inc., and Dimethaid Healthcare Ltd. Editorial, and funded by Covidien. Dr. Roth is a stockholder in Transdel Pharmaceuticals and a consultant and speaker for Covidien.