Cardiovascular and gastrointestinal safety of topical diclofenac gels

Abstract

This analysis assessed the rates of cardiac, vascular, and gastrointestinal (GI) adverse events (AEs) in osteoarthritis (OA) trials of topical diclofenac sodium 1% gel (DSG) and diclofenac diethylamine 1.16% gel (DEG). DSG trials included 5 placebo–controlled trials (3 knee [12 wk] and 2 hand [8 wk] OA) and 1 long-term (≤1 y), open-label study. DEG trials included a 3-week, placebo-controlled trial in knee OA, and a 3-week trial comparing DEG with oral ibuprofen in hand OA. In controlled trials, DSG (n=1121) and placebo (n=1088) had low rates of treatment-emergent cardiac (0.45% vs 0.28%, respectively), vascular (1.3% vs 1.2%), and GI AEs (5.2% vs. 4.4%). In the uncontrolled trial, rates of treatment-emergent cardiac, vascular, and GI AEs, respectively, were low in 719 patients applying DSG to 1 knee (1.4%, 2.2%, and 7.4%) and 228 patients treating both knees (0.4%, 2.2%, and 11.8%). In the DEG knee OA trial, 1 of 117 (0.85%) patients applying DEG and 1 of 120 (0.83%) applying placebo experienced a cardiac AE. No vascular AEs were reported. No DEG-treated patient and 2 (1.7%) placebo-treated patients reported GI AEs. In the hand OA trial, DEG (n=165) and ibuprofen (n=156) were associated with similar and low rates of cardiac (1.8% vs. 1.3%, respectively) and vascular (0.6% for each treatment) AEs. GI AEs were less frequent with DEG (9.2% vs. 14.1%). These results suggest that CV and GI AEs with topical diclofenac gels (DSG and DEG) occur at a rate similar to placebo in randomized controlled trials lasting 3−12 weeks. Cardiovascular and GI safety were maintained for up to 1 year. Supported by Endo Pharmaceuticals Inc.