Letter: effects of oxycodone and tapentadol dosage on gastrointestinal function

We are writing to comment on the doses selected in the study by Jeong and colleagues comparing tapentadol with oxycodone.1 In their study evaluating differential effects of tapentadol and oxycodone on gastrointestinal and colonic transit, the authors compared side effects of the two compounds based upon doses that have not been shown to be equally efficacious. Any comparison of gastrointestinal transit time for analgesics, or other effects of different treatments, should utilise doses that are expected to provide similar analgesic efficacy. The authors referenced published studies that show comparable efficacy of tapentadol IR 100 mg to oxycodone IR 15 mg (postbunionectomy model; i.e. a dose ratio of ~6.6:1),2 and of tapentadol IR 50 mg to oxycodone IR 10 mg (end-stage osteoarthritis model; i.e. a dose ratio of 5:1).3 Published studies have also shown that a 5:1 dose ratio of tapentadol extended release to oxycodone controlled release provides similar analgesic efficacy.4-6 In their study,1 however, Jeong and colleagues chose to compare the effects of tapentadol IR 75 mg t.d.s. with oxycodone IR 5 mg t.d.s. in healthy volunteers treated for 48 h. This represents a dose ratio of 15:1, which is a significant departure from the ratios in the referenced studies demonstrating comparable efficacy.2, 3 The authors did not provide a rationale for the doses studied. Using the doses selected, the authors compared oxycodone IR 5 mg to a dose of tapentadol IR 75 mg, which has been shown to have efficacy comparable to oxycodone IR 10–15 mg. Considering existing evidence on the relationship between doses and the incidence of observed side effects,7-9 the study as designed does not support the authors’ conclusion that ‘tapentadol may not have significant advantages over standard mu-opioids in terms of the potential to avoid upper gastrointestinal motor dysfunction’. Declaration of personal interests: M. Kim and G. Vorsanger are employees of and own stock in Janssen Pharmaceuticals, Inc. Declaration of funding interests: Writing support was provided by Cherie Koch, PhD of MedErgy and funded by Janssen Scientific Affairs, LLC.