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.

Addition of 100 mg of Tramadol to 40 mL of 0.5% Ropivacaine for Interscalene Brachial Plexus Block Improves Postoperative Analgesia in Patients Undergoing Shoulder Surgeries as Compared to Ropivacaine Alone-A Randomized Controlled Study.

Background and objectives: Brachial plexus block is commonly used in shoulder surgery, as it provides satisfactory surgical conditions and adequate postoperative pain control. However, there are contradictory reports regarding the addition of tramadol to the injected regional anesthetic solution. We performed a prospective randomized study to evaluate the effectiveness of tramadol as an adjuvant to ropivacaine during interscalene brachial plexus block and assess its impact on the opioid consumption and the early postoperative pain in patients that underwent shoulder surgery. Materials and Methods: Eighty patients scheduled for elective shoulder surgery and anesthesia via interscalene brachial plexus block were randomly divided into two groups. In group A (n = 40), a solution of 40 mL of ropivacaine 0.5% and 2 mL (100 mg) of tramadol was administered during the brachial plexus block, while in group B (n = 40), a solution of 40 mL of ropivacaine 0.5% and 2 mL NaCl 0.9% (placebo) was administered. The effectiveness and duration of sensory and motor blocks were recorded in both groups. The sensory block was assessed recording the loss of sensation to pin prick test over the skin distribution of the axillary, radial, and musculocutaneous nerves. The motor block was assessed using the modified 3-point Bromage score (0-2 points). Cumulative morphine consumption and pain, using the Visual Analog Scale (VAS), were evaluated in both groups at 2, 4, 8, and 24 h after surgery. Results: Sensory block onset was achieved earlier in group A than in group B (5.21 ± 3.15 minutes (min) vs. 7.1 ± 4.51 min, p = 0.029). The motor block onset was similar between the two groups (13.08 ± 6.23 min vs. 13.28 ± 6.59 min; p = 0.932). The duration of the sensory block was longer in group A as compared to group B (13 ± 2.3 h vs. 12 ± 2.8 h; p = 0.013). The duration of the motor block did not present any difference between the groups (10 ± 2.2 h vs. 10 ± 2.8 h; p = 0.308). Differences in morphine administration were not significant at 2, 4, and 8 h, however, morphine consumption was found to be decreased in group A 24 h postoperatively A (p = 0.04). The values of VAS were similar at 2, 4, and 8 h, however, they were lower in group A at 24 h (p < 0.013). Conclusions: Combined regional administration of tramadol and ropivacaine during interscalene brachial plexus block improves the time of onset and the duration of the sensory block, while it is associated with reduced morphine consumption during the first 24 h after shoulder surgery.

Development of a novel LC-MS/MS method for detection and quantification of tramadol hydrochloride in presence of some mislabeled drugs: Application to counterfeit study.

Counterfeiting of pharmaceuticals has become a serious problem all over the world, particularly in developing countries. In the present work, a highly sensitive LC-MS/MS method was developed for simultaneous determination of tramadol hydrochloride in the presence of some suspected mislabeled drugs such as alprazolam, diazepam, chlorpheniramine maleate, diphenylhydramine and paracetamol. The prepared samples were analyzed on an API 4000 mass spectrometer using an Eclipse C18 column (3.5 µm, 4.6 × 100 mm). The mobile phase consisting of 0.01% formic acid, acetonitrile and methanol (60:20:20 v/v/v) was pumped with an isocratic elution at a flow rate of 0.7 mL min-1 . The detection was achieved on a triple quadruple tandem mass spectrometer in multiple reaction monitoring mode. The proposed method was successfully validated according to International Conference on Harmonization guidelines with respect to accuracy, precision, linearity, limit of detection and limit of quantitation. The calibration linear range for tramadol hydrochloride, alprazolam, diazepam, chlorpheniramine maleate, diphenylhydramine and paracetamol was 5-500 ng mL-1 . The results revealed that the applied method is promising for the differentiation of genuine tramadol tablets from counterfeit ones without prior separation.

Analgesics in ophthalmic practice: a review of the oral non-narcotic agent tramadol.

This report reviews the causes of ocular pain and discusses the pharmacology, pharmacokinetics, efficacy, adverse effects, and dosage of tramadol, a novel non-narcotic oral analgesic. Tramadol is a synthetic analog of codeine with a dual mechanism of action that involves agonist activity at the mu opioid receptor, as well as inhibition of monoaminergic (norepinephrine and serotonin) re-uptake. Unlike opiate analgesics, tramadol has very low propensity toward physical dependence. Common dose-related adverse effects of tramadol include dizziness, nausea, vomiting, dry mouth, and/or drowsiness. Clinically, tramadol has been shown to be equivalent to acetaminophen (325 mg)-codeine (30 mg) combinations for the treatment of moderate or severe nonocular pain. Tramadol appears to be an effective analgesic agent for pain control due to postoperative surgical trauma, as well as in various chronic malignant and nonmalignant disease states. Tramadol has shown variable effectiveness in the control of pain related to dental procedures. The usefulness of tramadol in pain states from ophthalmic origin has yet to be clinically established.