(214) Symptoms of opioid withdrawal after discontinuation of tapentadol immediate release, an analgesic with mu-opioid receptor agonism

Tapentadol is a single molecule with a dual mode of action: mu-opioid receptor agonism and norepinephrine reuptake inhibition. The contribution of mu-opioid receptor agonism to opioid withdrawal symptoms following 90-days treatment with tapentadol immediate release (IR) was compared with oxycodone IR in a randomized, double-blind, multicenter trial of patients with low back pain or pain from osteoarthritis. Patients (878 randomized, 849 received study drug) 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. Withdrawal symptoms after abrupt study medication discontinuation were examined using the Clinical Opioid Withdrawal Scale (COWS) and the Subjective Opioid Withdrawal Scale (SOWS) questionnaires. Most patients completed these questionnaires within 2 to 4 days after study medication was discontinued and without replacement opioid therapy. Treatment with daily doses (mean ± SD) of tapentadol IR (284 ± 156 mg) and oxycodone IR (42 ± 25 mg) showed similar pain scores throughout the study. Based on the COWS assessment (n=306 tapentadol IR, 66 oxycodone IR), significantly fewer patients reported mild-to-moderate withdrawal symptoms in the tapentadol IR group (17%) than in the oxycodone IR group (29%; nominal P <0.05). The mean SOWS score was lower for the tapentadol IR group (6.9) than the oxycodone IR group (8.7, no significant difference). For patients assessed ≥5 days after study drug was discontinued (n=183 tapentadol IR, 43 oxycodone IR), the mean SOWS score was 6.3 and 7.0 for the tapentadol IR and oxycodone IR groups, respectively (no significant difference). These findings suggest in this patient population, opioid withdrawal was infrequent and of limited intensity after abrupt discontinuation of 90-day therapy. This study was supported by Johnson & Johnson Pharmaceutical Research and Development and Gruünenthal GmbH.