Abstract: We included three studies with 1853 participants who had undergone surgical removal of impacted wisdom teeth, hip replacement, or hysterectomy. The overall risk of bias across the three included studies was low, with unclear risk of bias in relation to the size of the three studies. Two studies did not report all our prespecified outcomes, which limited the analyses we could do. The proportion of participants achieving at least 50% pain relief over six hours with dexketoprofen 25 mg plus tramadol 75 mg was 66%, compared to 32% with placebo, giving an NNT of 3.0 (95% CI 2.5 to 3.7) (RR 2.1 (95% CI 1.7 to 2.4); 748 participants; 3 studies) (moderate quality evidence). The response rate with dexketoprofen 25 mg alone was 53% (RR 1.3 (95% CI 1.1 to 1.4); 744 participants; 3 studies) and with tramadol alone was 45% (RR 1.5 (95% CI 1.3 to 1.7); 741 participants; 3 studies) (moderate quality evidence). We downgraded the evidence because of some inconsistency in the results. The median time to use of rescue medication could not be estimated exactly, but was probably eight hours or more, indicating a long duration of effect (moderate quality evidence). We downgraded the evidence because it was not possible to estimate the effect exactly in the two multiple dose studies, resulting in imprecision. Fewer participants used rescue medication with higher doses of active treatment (summary statistic not calculated; 123 participants; 1 study) (very low quality evidence). We downgraded the evidence because the data came from a single study with few participants and events. Adverse events and serious adverse events were not reported consistently for the single dose phase of the studies. In the single dose study, 11% of participants experienced adverse events with dexketoprofen 25 mg plus tramadol 75 mg, which were mostly mild or moderate nausea, vomiting, or dizziness, and typical with these medicines. Rates were lower with placebo and lower doses (very low quality evidence). We downgraded the evidence because the data came from a single study with few participants and events. Information on multiple dosing over three and five days supported a low event rate with the combination. Overall, rates were generally low in all treatment arms, as they were for withdrawals for adverse events or other reasons. A single oral dose of dexketoprofen 25 mg plus tramadol 75 mg provided good levels of pain relief with long duration of action to more people than placebo or the same dose of dexketoprofen or tramadol alone. The magnitude of the effect was similar to other good analgesics. Adverse event rates were low. There is modest uncertainty about the precision of the point estimate for efficacy, but the NNT of 3 is consistent with other analgesics considered effective and commonly used.

Plain-language summary: In May 2016, we found three studies involving 1853 people. The main comparison was between the fixed-dose of dexketoprofen 25 mg plus tramadol 75 mg and placebo (a dummy treatment). The studies tested single doses after wisdom tooth extraction, hip replacement operations, and gynaecological (female reproductive system) operations. Studies included adults over a range of ages, and 7 out of 10 participants were women. The main outcome was the number of participants having at least half of the maximum possible pain relief over the first six hours after taking the tablets. All three studies reported the main outcome for dexketoprofen 25 mg plus tramadol 75 mg. There were 748 participants in the comparison with placebo. About 7 in 10 people achieved this outcome with dexketoprofen 25 mg plus tramadol 75 mg, compared with 3 in 10 with placebo. The combination was significantly better than placebo, and better than either dexketoprofen or tramadol alone. The pain relief lasted a long time, probably eight hours or more, but the exact duration could not be determined. Fewer people needed to take additional painkillers with the combination treatment than with placebo. About 1 in 10 people had side effects with dexketoprofen 25 mg plus tramadol 75 mg. These were mostly mild or moderate nausea (feeling sick), vomiting (being sick), and dizziness, which are typical with these medicines. Serious side effects were uncommon. Few people dropped out of the studies. We judged the quality of the evidence as moderate for the painkilling effect of dexketoprofen 25 mg plus tramadol 75 mg. For side effects we judged the quality of the evidence about a single dose as very low because there were so few participants and events, but we judged it as moderate when we included evidence from the three- and five-day studies. Moderate quality evidence means that more information might change our estimate of the effect. Very low quality evidence means that we are very uncertain about the results.