Effectivity And Safety Of Two Analgesic With Dual Mechanism(Oxycodone/ Acetaminophen And Tapentadol Immediate Release) For Postoperative Acute Moderate To Severe Pain Relief: A Systematic Review And Meta-analysis

Objective: To assess the efficacy and safety of the analgesic with dual mechanism?oxycodone/acetaminophen and tapentadol immediate release, IR? for postoperative acute moderate to severe pain relief and providing evidence for clinical practice. Methods: Randomized controlled trials?RCTs? on combination of oxycodone plus acetaminophen and tapentadol IR treating pain relief after surgery were searched from the following data-bases as Pub Med, EMbase, MEDLINE?Ovid?, the Cochrane Library, CNKI, and WANFANG from the date of their establishment to January 2016. The data of RCTs meeting the inclusive criteria were extracted according to Cochrane methods by two reviewers independently, and after the quality was evaluated and cross-checked, meta-analyses were conducted by using Rev Man 5.2 software. Search terms are oxycodone, acetaminophen, pain, postoperative, randomized controlled trial and Meta-analysis in systematic review of oxycodone/ acetaminophen; tapentadol, IR, immediate, pain, postoperative, randomised controlled trial and Meta-analysis in systematic review of tapentadol IR. Results:?1? A total of 19 studies involving 2213 patients were included. For the efficacy, compared with the placebo group, doses of 5mg/325 mg, 10mg/650 mg and 10mg/1000 mg of oxycodone/acetaminophen showed a significantly higher efficacy in the postoperative acute moderate to severe pain relief?all P<0.00001?; and doses of 5mg/500 mg, 5mg/1000 mg and 10mg/350 mg of oxycodone/acetaminophen were significantly higher than the equal dose oxycodone alone?5mg, 10mg? in the pain relief?RR=1.79, 95%CI [1.36, 2.36], P<0.00001, I2=0%?. Doses of 10mg/350 mg and 10mg/1000 mg of oxycodone/acetaminophen had not a significant difference compared with the higher dose oxycodone alone?20mg, 30mg? in the pain relief?RR=1.26, 95%CI [0.96, 1.64], P=0.09, I2=29%?; doses of 5mg/325 mg, 10mg/650 mg and 10mg/1000 mg of oxycodone/acetaminophen were significant lower than placebo in the participants using rescue medication?all P<0.01?, however, the oxycodone/acetaminophen group had not a significant difference compared with the oxycodone alone group or the acetaminophen alone group in the participants using rescue medication?P>0.05?. As for the oral surgery, doses of 5mg/325 mg, 10mg/650 mg and 10mg/1000 mg of oxycodone/acetaminophen groups were significantly higher than placebo group for the pain relief?all P<0.01?. In addition, the RR of oxycodone 10mg/acetaminophen 650 mg and placebo for pain relief was higher than the other 2 doses of combination, moreover, there were more articles were enrolled and the low heterogeneity of which lead to a high reliability among the three kinds of doses of oxycodone/ acetaminophen. As for the participants using rescue medication, the combinations of oxycodone/acetaminophen was significantly less than placebo?all P<0.01?, In additional, the RR of participants using rescue medication of oxycodone 10mg/acetaminophen 650 mg and placebo was less than the other 2 doses of combination. Adverse events occurred more frequently with combination therapy than placebo or acetaminophen alone group, but were generally described as mild to moderate in severity and rarely led to withdrawal. In addition, there was no significant difference in the adverse events between the oxycodone/acetaminophen group and the oxycodone alone group.?2? Nine trials including 3961 patients were analyzed. In this meta-analysis, for moderate to severe pain relief, compared with placebo, a significant improvements in moderate to severe pain relief on sum of pain intensity difference over 48 hours(SPID₄₈) scores were observed with 50, 75, and 100 mg doses of tapentadol IR?all P<0.005?. Compared with oxycodone hydrochloride?HCL? IR 10 mg, the tapentadol IR 50 mg showed numerically lower pain relief on both SPID₄₈ and total pain relief over 48 hours?TOTPAR48? scores, however, there was no statistically significant difference?all p>0.05?. Also, there was no statistically significant difference between tapentadol IR 75 mg and oxycodone HCL IR 10 mg on both SPID₄₈ and TOTPAR48 scores?all p>0.05?. There was also no statistically significant difference between tapentadol IR 100 mg and oxycodone HCL IR 10 mg on SPID₄₈?WMD-8.30, 95% CI-72.22 to 55.62, p=0.80?, while tapentadol IR 100 mg provided significantly higher scores on TOTPAR48?WMD 9.40, 95% CI 2.56 to 16.24, p=0.007?. In addition, compared with the tapentadol IR 50 mg, tapentadol IR 75 mg demonstrated significant improvement in moderate to severe pain relief based on both SPID₄₈ and TOTPAR48 scores?all P<0.05?. For total AEs incidence, the tapentadol IR 50 and 75 mg were significantly lower than oxycodone HCL IR 10 mg. Especially, the incidence of nausea and constipation were significantly lower in patients treated with either tapentadol IR 50 or 75 mg compared with patients treated with oxycodone HCL IR 10 mg?all P<0.05?. However, tapentadol 100 mg led to a similar incidence of gastrointestinal AEs?all P<0.05? and increased an incidence of nervous systematic AEs than oxycodone HCI IR 10 mg?all P<0.05?. Conclusions:?1? The present study showed that all doses of combinations of oxycodone/acetaminophen were effective and high safe in postoperative acute pain relief. In addition, we suggest that the combination of oxycodone 10 mg plus acetaminophen 650 mg might be better suited for the dental postoperative acute pain relief.?2? This study suggested that the tapentadol IR 75 mg might be an optimal medication for moderate to severe pain control with fewer side effects in three doses of tapentadol IR and the tapentadol IR could provide comparable efficacy than the oxycodone HCI IR 10 mg.?3? Finally, the oxycodone/acetaminophen could provided a better acute pain relief than the tapentadol IR. However, the tapentadol IR was suited for using with longer time because of its advantage in adverse effects.