Tapentadol extended-release for treatment of chronic pain: a review

Journal of Pain Research Dovepress open access to scientific and medical research Review Open Access Full Text Article Journal of Pain Research downloaded from https://www.dovepress.com/ by 213.32.59.119 on 12-Jul-2018 For personal use only. Tapentadol extended-release for treatment of chronic pain: a review This article was published in the following Dove Press journal: Journal of Pain Research 29 July 2011 Number of times this article has been viewed Nalini Vadivelu 1 Alexander Timchenko 1 Yili Huang 2 Raymond Sinatra 1 Department of Anesthesiology, Yale University School of Medicine, New Haven, CT; 2Internal Medicine, North Shore-LIJ Plainview Hospital, Plainview, NY, USA 1 Background Correspondence: Nalini Vadivelu Department of Anesthesiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA Tel +1 204 785 2802 Fax +1 203 785 8884 Email submit your manuscript | www.dovepress.com Dovepress http://dx.doi.org/10.2147/JPR.S14842 Powered by TCPDF (www.tcpdf.org) Abstract: Tapentadol is a centrally acting analgesic with a dual mechanism of action of mu receptor agonism and norepinephrine reuptake inhibition. Tapentadol immediate-release is approved by the US Food and Drug Administration for the management of moderate-to-severe acute pain. It was developed to decrease the intolerability issue associated with opioids. Tapentadol extended-release has a 12-hour duration of effect, and has recently been evaluated for pain in patients with chronic osteoarthritis, low back pain, and pain associated with diabetic peripheral neuropathy. Tapentadol extended-release was found to provide safe and highly effective analgesia for the treatment of chronic pain conditions, including moderate-to-severe chronic osteoarthritis pain and low back pain. Initial trials demonstrating efficacy in neuropathic pain suggest that tapentadol has comparable analgesic effectiveness and better gastrointestinal tolerability than opioid comparators, and demonstrates effectiveness in settings of inflammatory, somatic, and neuropathic pain. Gastrointestinal intolerance and central nervous system effects were the major adverse events noted. Tapentadol will need to be rigorously tested in chronic neuropathic pain, cancer-related pain, and cancer-related neuropathic pain. Keywords: osteoarthritis, neuropathic pain, analgesic, opioids, norepinephrine Centrally acting analgesics with a dual mechanism of action have recently been developed in an attempt to reduce the tolerability issues associated with opioids while providing equivalent analgesia, and are being evaluated for the treatment of chronic pain. Tapentadol is a novel centrally acting analgesic, initially formulated as an immediate-release preparation. It is a potent Schedule II analgesic approved for use by the US Food and Drug Administration (FDA) in 2009, and is the first pain reliever developed in over 25 years for the management of moderate-to-severe acute pain. Tapentadol immediate-release is available as 50, 75, and 100 mg tablets and provides 4–6 hours of analgesia. Tapentadol immediate-release was shown to provide analgesia comparable with that of 10–15 mg of immediate-release oxycodone1,2 in patients recovering from dental extraction pain3 and pain following bunionectomy.4–6 It was also as effective as oxycodone in patients presenting with chronic osteoarthritis pain and chronic low back pain.7,8 Of importance in the comparator trials was the finding that patients treated with tapentadol had a lower incidence of adverse gastrointestinal events, including nausea, vomiting, and constipation, than those treated with oxycodone. In a bunionectomy trial, the composite incidence of nausea and vomiting in patients treated with tapentadol 50 mg every 6 hours was significantly lower than in patients treated with oxycodone 10 mg. Based on the safety and efficacy profile of the immediate-release Journal of Pain Research 2011:4 211–218 211 © 2011 Vadivelu et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. Journal of Pain Research downloaded from https://www.dovepress.com/ by 213.32.59.119 on 12-Jul-2018 For personal use only. Vadivelu et al preparation, the Pricara division of Johnson and Johnson Pharmaceuticals made the decision to develop a preparation that provided a more prolonged duration of effect in an indication of chronic pain. The new preparation, tapentadol extended-release (ER), is a sustained-release tablet with a 12-hour duration of effect for patients 18 years of age and older with moderate-to-severe chronic pain who require around the clock analgesic therapy. At the time of writing, clinical development of tapentadol ER has been completed, submitted, and reviewed by the FDA. The submission included a number of large-scale, randomized, active comparator-controlled and placebo-controlled Phase III studies that evaluated the safety and efficacy of tapentadol in patients with chronic osteoarthritis, low back pain, or pain associated with diabetic peripheral neuropathy. Tapentadol ER has also been evaluated in a 1-year, activecontrolled, open-label Phase III safety trial. The FDA has not requested additional efficacy trials, but in a complete response letter provided on November 2010, the agency seeks additional information regarding modifications to the ER tablet that increase mechanical resistance to breaking or crushing prior to granting approval for use. In a series of largescale, controlled clinical trials, tapentadol ER was found to provide safe and highly effective analgesia for the treatment of chronic pain conditions, including moderate-to severe chronic osteoarthritis pain and lower back pain.1,2,4 Like the immediate-release preparation, it provides potent analgesia equivalent or superior to that of sustained-release opioids with an unexpected reduction in adverse gastrointestinal events. It also appears to have analgesic effectiveness comparable with that of opioid comparators, demonstrating effectiveness in settings of inflammatory, somatic, and neuropathic pain. Pharmacology Tapentadol produces potent analgesic effects via its dual mechanism of action, ie, mu receptor agonism and norepinephrine reuptake inhibition.9–12 In animal models, tapentadol behaves as a weak opioid agonist, with 50 times less affinity than morphine for the mu receptor. Despite this low binding affinity, tapentadol provides powerful analgesic effects, equivalent to one third that observed with equianalgesic doses of morphine.2,13 This finding and observations noted in Phase I human trials suggested that mu receptor activation provides a measurable but limited contribution to the analgesic effect of tapentadol. Norepinephrine inhibits transmission of noxious impulses by activating alpha adrenergic receptors located 212 Powered by TCPDF (www.tcpdf.org) submit your manuscript | www.dovep (...truncated)