Dexketoprofen/tramadol (25 mg/75 mg) is a new oral fixed-dose combination offering a comprehensive multimodal approach to moderate-to-severe acute pain that encompasses central analgesic action, peripheral analgesic effect and anti-inflammatory activity, together with a good tolerability profile. The analgesic efficacy of dexketoprofen/tramadol combination is complemented by a favorable pharmacokinetic and pharmacodynamic profile, characterized by rapid onset and long duration of action. This has been well documented in both somatic- and visceral-pain human models. This review discusses the available clinical evidence and the future possible applications of dexketoprofen/tramadol fixed-dose combination that may play an important role in the management of moderate-to-severe acute pain.

ObjectivesTo compare efficacy/safety of oral tramadol 75 mg/dexketoprofen 25 mg (TRAM/DKP) and TRAM 75 mg/paracetamol 650 mg (TRAM/paracetamol) in moderate to severe pain following surgical removal of impacted lower third molar.DesignMulticentre, randomised, double-blind, placebo-controlled, phase IIIb study.ParticipantsHealthy adult patients scheduled for surgical extraction of at least one fully/partially impacted lower third molar requiring bone manipulation. 654 patients were randomised and 653 were eligible for analysis.InterventionsSurgery was performed under local anaesthetic. No sedation was permitted. Patients rated pain intensity (PI) using an 11-Numerical Rating Scale (NRS) (0 no pain; 10 worst pain). Participants experiencing moderate/severe pain (≥4) within 4 hours of surgery were randomised (2:2:1 ratio) to a single oral dose of TRAM/DKP 75/25 mg, TRAM/paracetamol 75/650 mg or placebo.Main outcome measuresEfficacy was based patients’ electronic diaries. Analgesia and pain were recorded as follows: pain relief (PAR) on a 5-point Verbal Rating Scale (0=‘no relief’, 1=‘a little (perceptible) relief’, 2=‘some (meaningful) relief’, 3=‘lot of relief’, 4=‘complete relief’) at the predefined postdose time points t15 min, t30 min, t1 hour, t1.5 hour, t2 hour, t4 hour, t6 hour and t8 hour and PI on the 11-point NRS at t0 and at the same predefined postdose time points. Onset of analgesia documented using double stopwatch method over a 2-hour period. Primary endpoint was total pain relief over 6 hours (TOTPAR6). Rescue medication was available during the treatment period.ResultsTRAM/DKP was superior to TRAM/paracetamol and placebo at the primary endpoint TOTPAR6 (p<0.0001). Mean (SD) TOTPAR6 in the TRAM/DKP group was 13 (6.97), while those in the active control and placebo groups were 9.1 (7.65) and 1.9 (3.89), respectively. Superiority of TRAM/DKP over active comparator and placebo was observed at all secondary endpoints. Incidence of adverse events was comparable between active groups.ConclusionsTRAM/DKP (75/25 mg) is effective and superior to TRAM/paracetamol (75/650 mg) in relieving moderate to severe acute pain following surgical removal of impacted lower third molar, with a faster onset of action, greater and durable analgesia, together with a favourable safety profile.Trial registration numberEudraCT 2015-004152-22 and NCT02777970.

IntroductionIn 2016, the orally administered fixed-dose combination of dexketoprofen 25 mg and tramadol 75 mg (DKP/TRAM FDC) was approved in Europe for short-term treatment of moderate-to-severe acute pain, an indication that encompasses a wide range of post-operative and non-surgical painful conditions. This has suggested the necessity to have a clearer indication on its clinical use, with the support of expert pain clinicians, working in different medical specialities, and reinforced by the data present in the literature.MethodsWith the aim of assisting clinicians in the use of DKP/TRAM FDC in daily practice, two rounds of a modified Delphi process were conducted. In the first round, a board of nine experts developed a series of consensus statements based on available evidence, and their clinical experience, with DKP/TRAM FDC. In the second round, 75 clinicians with extensive experience in pain management expressed individually their agreement with the statements, using a dedicated online platform. Consensus was defined as at least 70% agreement.ResultsTwenty-eight statements were developed. Of these, 19 reached the defined level of consensus.ConclusionThe agreed consensus statements may assist clinicians in applying the results of clinical studies and clinical experience to routine care settings, providing guidance for use of this new analgesic combination in moderate-to-severe post-operative and non-surgical acute pain.FundingMenarini Group.Electronic supplementary materialThe online version of this article (10.1007/s12325-019-01096-0) contains supplementary material, which is available to authorized users.

The authors aimed to test potential relations between osteoarthritis (OA) features, disability and health-related quality of life (HR-QoL) at different body locations. Outpatients consulting for pain associated to self-reported OA at varied healthcare settings were evaluated in a 3-month observational non-controlled follow-up study. Socio-demographic/anthropometric and medical data were collected at three time points. Lequesne's indices, quick-disabilities of arm, shoulder and hand (DASH) and Oswestry questionnaires provided measures of physical function and disability. HR-QoL measures were obtained with EuroQol-5 Dimensions. Multivariate analyses were used to evaluate the differences of pain severity across body regions and the correlates of disability and HR-QoL. Six thousand patients were evaluated. Pain lasted 2 years or more in 3995 patients. The mean pain severity at baseline was moderate (6.4 points). On average, patients had pain in 1.9 joints/areas. The pain was more severe when OA involved the spine or all body regions. Pain severity explained much of the variance in disability and HR-QoL; this association was less relevant in patients with OA in the upper limbs. There were considerable improvements at follow up. Pain severity improved as did disability, which showed particularly strong associations with HR-QoL improvements. Pain severity is associated with functional limitations, disability and poor HR-QoL in patients with self-reported OA. Functional limitations might have particular relevance when OA affects the upper limbs. Improvements are feasible in many patients who consult because of their pain.

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