The ER tapentadol preparation was specifically developed for the management of moderate-to-severe chronic pain. The controlled release formulation provides a 12-hour duration of activity, as well as the convenience and analgesic uniformity associated with twice per day dosing. The analgesic efficacy of tapentadol is comparable with that of the classic ER opioids, such as controlled-release oxycodone. Opioids have efficacy in inflammatory, somatic, and neuropathic pain conditions, as well as cancer pain. Based on several large-scale clinical trials, described later in this paper, tapentadol ER is associated with better gastrointestinal tolerability, than the typical extended-duration opioids.
Mu receptor activation is a secondary mechanism responsible for the analgesic effect of tapentadol. Therefore, with chronic use, there is a relatively low degree of mu receptor activation as compared with potent mu opioids and, correspondingly, a slower onset of tolerance. One study demonstrated that the onset of tolerance with chronic use of tapentadol was significantly delayed as compared with morphine. With morphine treatment, the onset of tolerance was almost immediate, with complete tolerance by day 21. With tapentadol use, a progressive decline in efficiency was observed until day 18, followed by a plateau of moderate antinociception and complete tolerance on day 51. It is unclear whether benefits of reduced tolerance and dose escalation will be observed with long-term clinical use.