Tapentadol immediate release is associated with improved gastrointestinal tolerability compared with oxycodone immediate release over 90 days in patients with lower back or osteoarthritis pain

Tapentadol is a novel, single-molecule analgesic with a dual mode of action: mu-opioid receptor agonism and norepinephrine reuptake inhibition. A randomized, double-blind, active-control, parallel group, multicenter trial of patients with low back pain or pain from osteoarthritis of the knee or hip studied the tolerability of long-term exposure (90 days) to tapentadol immediate release (IR). Patients (N = 878) were randomly assigned in a 4:1 ratio to a flexible dose of either tapentadol IR (50 or 100 mg/dose; maximum 600 mg/day) or oxycodone IR (10 or 15 mg/dose; maximum 90 mg/day) every 4 to 6 hours. Study drug was not taken by 29 patients who were excluded from all analyses. The Cochran-Mantel-Haenszel test was used to estimate odds ratios for treatment-emergent nausea, vomiting, constipation, somnolence, and dizziness. Both treatment groups showed similar pain scores throughout the study. Treatment-emergent adverse events (TEAEs) in the tapentadol IR group (76%) were lower than in the oxycodone IR group (83%). The most common TEAEs for both groups were nausea, vomiting, dizziness, constipation, headache, and somnolence. The incidences of nausea, vomiting, constipation, and the composite of nausea/vomiting were significantly lower in the tapentadol IR group than in the oxycodone IR group (P <0.001 for all treatment comparisons). The odds ratios and corresponding confidence intervals for nausea, vomiting, constipation, and composite of nausea/vomiting were 0.542 (0.37, 0.79), 0.476 (0.32, 0.70), 0.396 (0.26, 0.59), and 0.458 (0.33, 0.65), respectively; indicating more favorable incidence rates for the tapentadol IR group compared with the oxycodone IR group. The incidences of somnolence or dizziness were not significantly different between the treatment groups. These findings show tapentadol IR is associated with substantially improved gastrointestinal tolerability compared with oxycodone IR at doses providing similar pain relief. This study was supported by Johnson & Johnson Pharmaceutical Research and Development and Grünenthal GmbH.