Expert Consensus on Clinical Use of an Orally Administered Dexketoprofen Plus Tramadol Fixed-Dose Combination in Moderate-To-Severe Acute Pain: A Delphi Study.

INTRODUCTION: In 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. METHODS: With 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. RESULTS: Twenty-eight statements were developed. Of these, 19 reached the defined level of consensus. CONCLUSION: The 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. FUNDING: Menarini Group.

Correction to: Cue-Signal-Response Analysis in 3D Chondrocyte Scaffolds with Anabolic Stimuli.

This erratum is to add the following paragraph in the Acknowledgement section.

Cue-Signal-Response Analysis in 3D Chondrocyte Scaffolds with Anabolic Stimuli.

Articular cartilage is an avascular connective tissue responsible for bearing loads. Cell signaling plays a central role in cartilage homeostasis and tissue engineering by directing chondrocytes to synthesize/degrade the extracellular matrix or promote inflammatory responses. The aim of this paper was to investigate anabolic, catabolic and inflammatory pathways of well-known and underreported anabolic stimuli in 3D chondrocyte cultures and connect them to diverse cartilage responses including matrix regeneration and cell communication. A cue-signal-response experiment was performed in chondrocytes embedded in alginate scaffolds subjected to a 9-day treatment with 7 anabolic cues. At the signaling level diverse pathways were measured whereas at the response level glycosaminoglycan (GAG) synthesis and cytokine releases were monitored. A significant increase of GAG was observed for each stimulus and well known anabolic phosphoproteins were activated. In addition, WNK1, an underreported protein of chondrocyte signaling, was uncovered. At the extracellular level, inflammatory and regulating cytokines were measured and DEFB1 and CXCL10 were identified as novel contributors to chondrocyte responses, both closely linked to TLR signaling and inflammation. Finally, two new pro-growth factors with an inflammatory potential, Cadherin-11 and MGP were observed. Interestingly, well-known anabolic stimuli yielded inflammatory responses which pinpoints to the pleiotropic roles of individual stimuli.

Multimodal analgesia in moderate-to-severe pain: a role for a new fixed combination of dexketoprofen and tramadol.

BACKGROUND: Untreated and under-treated pain represent one of the most pervasive health problems, which is worsening as the population ages and accrues risk for pain. Multiple treatment options are available, most of which have one mechanism of action, and cannot be prescribed at unlimited doses due to the ceiling of efficacy and/or safety concerns. Another limitation of single-agent analgesia is that, in general, pain is due to multiple causes. Combining drugs from different classes, with different and complementary mechanism(s) of action, provides a better opportunity for effective analgesia at reduced doses of individual agents. Therefore, there is a potential reduction of adverse events, often dose-related. Analgesic combinations are recommended by several organizations and are used in clinical practice. Provided the two agents are combined in a fixed-dose ratio, the resulting medication may offer advantages over extemporaneous combinations. CONCLUSIONS: 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.