Letter: effects of oxycodone and tapentadol dosage on gastrointestinal function – author's reply

Abstract

I thank Drs Kim and Vorsanger for their interest in our randomised placebo controlled trial of oxycodone and tapentadol on gastrointestinal transit.1, 2 Our interest in conducting this pharmacodynamic study was peaked by the intriguing differences in gastrointestinal side effects of tapentadol in clinical trials, to which we refer in the paper and in my recent review on the management or avoidance of opiate bowel dysfunction.3 Given the actions of tapentadol as μ opiate agonist and norepinephrine reuptake inhibitor, both of which may inhibit gastrointestinal motility, I had written: ‘Studies of the pharmacodynamic effects of tapentadol on gastric emptying and colonic transit would be of significant interest’.3 In this controlled study funded by Mayo Clinic, placebo served as negative control, and we selected the 5 mg oxycodone dose as a positive control, correctly predicting it would retard gastrointestinal transit. The approved doses of tapentadol IR for acute moderate to severe pain are 50 mg, 75 mg or 100 mg orally every 4–6 h. We chose a conservative middle dose administered three rather than four or six times in 24 h. The ratio of the doses of the two drugs is irrelevant, as each was tested at a clinically relevant dose and compared to placebo. Our statistical analysis statement prespecified the a priori contrasts: tapentadol and oxycodone vs. placebo. We stand by the objective conclusions of our study: at a dose that will be typically used in clinical practice (75 mg t.d.s.), tapentadol also retards gastric emptying and small bowel transit of solids. We encourage Janssen Scientific Affairs to commission dose-response studies with tapentadol to clarify whether there is a dose of tapentadol IR or ER that does not delay gastric emptying. The authors’ declarations of personal and financial interests are unchanged from those in the original article.2