Safety and tolerability of tapentadol extended release (ER) versus oxycodone controlled release (CR) in elderly patients with chronic low back or osteoarthritis pain

Abstract

In a phase 3, randomized, open-label, 1-year safety study in adults with moderate-to-severe chronic low back or osteoarthritis pain, tapentadol ER (100-250mg bid) provided similar pain relief to oxycodone HCl CR (20-50mg bid), with improved gastrointestinal tolerability (ClinicalTrials.gov Identifier:NCT00361504). This post-hoc analysis evaluated incidences of and study discontinuations due to overall and gastrointestinal treatment-emergent adverse events (TEAEs) among patients ≥65 years of age. Times to onset of and discontinuations due to constipation, nausea, or vomiting were estimated using Kaplan-Meier plots (treatment differences compared using the log-rank test); the percentage of treatment days with these TEAEs was calculated (treatment differences compared using the Wilcoxon test). Of 1,117 patients analyzed for safety, 312 were ≥65 years (tapentadol ER, n=245; oxycodone CR, n=67). Among patients ≥65 years in the tapentadol ER and oxycodone CR groups, respectively, 87.8% and 94.0% of patients reported ≥1 TEAE and 57.6% and 76.1% of patients reported gastrointestinal TEAEs (most were mild or moderate). Patients ≥65 years who received tapentadol ER versus oxycodone CR experienced significantly lower percentages of treatment days with nausea (5.39% vs 14.0%), vomiting (2.4% vs 7.2%), or constipation (14.9% vs 31.6%); all nominal P≤0.0021. Times to first onset of these TEAEs were significantly longer with tapentadol ER versus oxycodone CR (all nominal P≤0.0002 [log-rank test]). In the tapentadol ER and oxycodone CR groups, respectively, any TEAE led to study discontinuation in 33.1% and 49.3% and gastrointestinal TEAEs led to study discontinuation in 14.3% and 31.3% of patients ≥65 years. Times to withdrawal due to nausea, vomiting, or constipation were significantly longer with tapentadol ER versus oxycodone CR (all nominal P≤0.0099). Tapentadol ER was associated with better gastrointestinal tolerability and a lower rate of study discontinuations due to TEAEs than oxycodone CR in patients ≥65 with moderate-to-severe chronic pain. (OMJSA and Grünenthal GmbH supported this study.)