The efficacy and tolerability of multiple-dose tapentadol immediate release for the relief of acute pain following orthopedic (bunionectomy) surgery

Abstract

C o p y r i g h t I n f o r m a U K L i m i t e d 2 0 0 8 N o t f o r S a l e o r C o m e r c i a l D i s t r i b u t i o n U n a u t h o r i z e d u s e p r o h i b i t e d . A u t h o r i s e d u s e r s c a n d o w n l o a d , A B S T R A C TObjective: Tapentadol is a new, centrally acting analgesic with two mechanisms of action, combining m-opioid agonism and norepinephrine reuptake inhibition in a single molecule. This study assessed tapentadol immediate release (IR) in patients with postsurgical orthopedic pain.Methods: This randomized, double-blind, phase II study involved patients with moderate-to-severe pain after bunionectomy surgery (first metatarsal with osteotomy). Patients (N ¼ 269) were randomly assigned to receive tapentadol IR 50 or 100 mg, oxycodone HCl IR 10 mg, or placebo; the study drug was taken every 4-6 h, over a 72-h period starting 1 day after surgery (Evaluation Day 2). The primary endpoint was the sum of pain intensity over 24 h (SPI-24) on the second day after randomization (Evaluation Day 3). Potential limitations of this study included the use of rescue medication and the fact that it was not powered to statistically compare between-group differences in tolerability measures. Results: Mean (standard deviation [SD]) SPI-24 values on Evaluation Day 3 were significantly lower for tapentadol IR (50 mg: 33.6 [19.7], p ¼ 0.0133; 100 mg: 29.2 [15.2], p ¼ 0.0001) and oxycodone HCl IR 10 mg (35.7 [17.2]; nominal p ¼ 0.0365) compared with placebo (41.9 [17.7]). The most common treatment-emergent adverse events for all treatment groups were characteristic of drugs with m-opioid agonist activity. While providing similar analgesic efficacy, tapentadol IR 50 mg was associated with lower rates of nausea (46.3% vs. 71.6% for oxycodone HCl IR 10 mg), dizziness (32.8% vs. 56.7%), vomiting (16.4% vs. 38.8%), and constipation (6.0% vs. 17.9%), and a similar rate of somnolence (28.4% vs. 26.9%) compared with oxycodone HCl IR 10 mg.Conclusions: Tapentadol IR 50 and 100 mg and oxycodone HCl IR 10 mg were effective in this study for the relief of acute postoperative pain following bunionectomy. The study results suggest improved gastrointestinal tolerability of tapentadol IR 50 mg compared with oxycodone at a dose showing comparable efficacy.

Acute postoperative pain relief with immediate-release tapentadol: randomized, double-blind, placebo-controlled study conducted in South Korea

“…The results of pain intensity and pain relief assessments were supported by the study's other measurements of analgesia efficacy, including time to first use of rescue medication and PGIC, underscoring the robust nature of the study findings. Our results are in line with those of studies of tapentadol IR for treating acute pain in primarily nonAsian patients, showing statistically significant separation from placebo 18,19,22 p 0.001 for each tapentadol dose group vs. placebo) in a study population of primarily white, black, and Hispanic patients 19 . The investigators also reported statistically significant between-group differences for pain relief, as assessed by TOTPAR score at time points between 12 and 72 hours 19 , that were comparable to those observed in our Asian patients.…”

“…Tapentadol is also approved as an oral solution (OS) for the relief of acute pain in adults (US and EU). Clinical trials of patients with various types of moderate to severe acute pain have shown that tapentadol IR provides analgesia comparable to that of the pure m-opioid agonist, oxycodone IR, with improved gastrointestinal tolerability (lower incidence of nausea, vomiting, constipation) [18][19][20][21][22] . Inter-ethnic differences in the pain experience and its treatment have been reported.…”

Comparable efficacy and superior gastrointestinal tolerability (nausea, vomiting, constipation) of tapentadol compared with oxycodone hydrochloride

“…(17) 9 (5) 11 (7) 93 (34) 29 (18) 26 (17) 127 (46) 35 (21) 31 (20) 160 (57) 70 (41) 57 (40) Constip -ation 1 (1) 4 (2) 22 (15) 22 (8) 7 (4) 21 (14) 15 (5) 11 (7) 28 (18) 31 (11) 45 (26) 42 (29) Vomiting 0 7 (4) 1 (1) 34 (12) 11 (7) 7 (5) 77 (28) 23 (14) 13 (8) 72 (26) 59 (34) 34 (24) during the ER-treatment phase were also higher in the oxycodone HCl CR group than in the tapentadol ER group.…”

Management of opioid-induced constipation

“…Morphine is associated with a higher incidence of GI side effects than many other opioids (Cook et al, 2008;Ishihara et al, 2012). Tapentadol, which is a μ opioid agonist that also inhibits norepinephrine reuptake, was as effective as oxycodone for managing chronic moderate to severe skeletal pain (Lange et al, 2010), but has fewer side effects (Stegmann et al, 2008). The incidence of constipation is lower for transdermal fentanyl than an equianalgesic dose of oral morphine (Tassinari et al, 2008).…”

“…For example, although codeine, oxycodone and tapentadol all cause constipation, only codeine delays colonic transit (Gonenne et al, 2005;Jeong et al, 2012). When compared to oxycodone, tapentadol appears to cause less constipation, nausea and vomiting (Stegmann et al, 2008).…”