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Objectives: A substantial proportion of patients with chronic noncancer pain (CNCP) are treated with tapentadol (TAP) or oxycodone/naloxone (OXN) to improve their perceived physical and mental health over time., Methods: A cross-sectional study was conducted in 135 CNCP outpatients with usual prescribing (TAP: n = 58, OXN: n = 77) at a tertiary-care Spanish Hospital to compare health-related quality-of-life (HRQoL) records. Health utility was derived from the EQ-5D-3L. Regression models were performed to search for other HRQoL determinants. Pain intensity, relief, analgesic prescription, adverse events, inpatient stays, emergency department visits, and change to painkiller prescriptions were registered from electronic records., Results: Health utility (0.43 ± 0.24 scores, from -0.654 to 1) was similar for both opioids, although TAP showed a significantly low daily opioid dose requirement, neuromodulators use, and constipation side effect compared with OXN. After multivariable adjustment, the significant predictors of impaired HRQoL were pain intensity (β = -0.227, 95% CI -0-035 to -0.005), number of adverse events (β = -0.201, 95% CI -0.024 to -0.004), and opioid daily dose (β = -0.175, 95% CI -0.097 to -0.012). Male sex (β = -0.044) and pain relief (β = 0.158) should be taken into account for future studies., Conclusions: HRQoL was similar for TAP and OXN in real-world patients with CNCP, albeit with a TAP opioid-sparing effect. More work is needed to explore HRQoL determinants in relation to long-term opioid use in CNCP., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Tapentadol is a unique opioid analgesic due to its dual mechanism of action. Compared to other opioids with a classical mechanism of action, its analgesic potential is not far behind them, and its advantages are: a better safety profile in terms of a lower potential for drug-drug interactions and a lower potential for causing adverse events, and it is safe to use in sensitive populations. Tapentadol in the form of a immediate release formulation is an adequate drug of choice for achieving a pharmacotherapeutic analgesic response in acute pain conditions, while in the form of a extended release formulation it is an adequate pharmacotherapeutic analgesic solution for chronic pain syndromes of various etiology. Due to the specificity of the mechanism of action, tapentadol adequately relieves both pain components - nociceptive and neuropathic, and has an indication area for mixed pain syndrome as well. Based on this, the need for the use of co-analgesics is reduced, and thus the incidence of possible interactions and adverse events is reduced.

Objective: We aimed to compare the analgesic effectiveness of intranasal tapentadol nasal spray 44.5 mg and intravenous (IV) paracetamol 1 gm during the postoperative period in patients undergoing lower limb orthopedic surgeries under spinal anesthesia., Methods: This prospective, randomized, single-blind clinical trial was carried out in a tertiary care teaching hospital. Patients aged between 18 and 60 years of physical status ASA grade 1-3 were included in the study. Postoperative pain scores were measured using the visual analog scale (VAS) in centimeters (cm) every 12 hours in 37 patients per group. The patients were administered either intranasal tapentadol or IV paracetamol every 6 hours for 72 hours, beginning 3 hours after surgery., Results: There was a significant group by intervention effect favoring intranasal tapentadol, suggesting a greater reduction in VAS pain scores after the intervention at 72 hours (estimate: -1.58 cm; SE:0.2; P<0.001). Group by time effect for all the measured time frames, except for 36 hours, favored intranasal tapentadol with estimated values for greater reduction in VAS pain scores ranging from -0.8 cm to -1.6 cm., Discussion: The results of the present study suggests that intranasal tapentadol results in a greater reduction of postoperative pain compared with IV paracetamol in lower limb orthopedic surgeries. The ease of administration of tapentadol may make it a preferred option over IV paracetamol in such surgeries., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Tapentadol is a drug of choice for neuropathic cancer pain. DN4 questionnaire quickly determines neuropathic pain component. The aim of this study is to determine the correlation between neuropathic malignant pain component by applying tapentadol antidolorose pharmacotherapy in combination with palliative radiotherapy of osseous neuropathic metastatic changes in breast cancer patients before and after palliative radiotherapy. Methods: The first patients group comprised 30 patients with primary breast cancer and proved painful bone secondary deposits with neuropathy for which tapentadol was prescribed, and they underwent palliative radiotherapy. The second group comprised 30 patients with primary breast cancer and proved painful bone metastases with neuropathy treated only with palliative antidolorose radiotherapy. Key findings : After two-months-follow up, tapentadol group patients had lower DN4 score values (Z=2,021; p=0.043). Significantly lower number of tapentadol group patients was without neuropathic pain after a three-month-follow up (χ ²=5,711; p=0.017). Significantly greater number of tapentadol group patients had best ECOG score 0 ( χ² =7,486; p=0.023). There was statistically significant positive correlation between tapentadol dose and DN4 score in patients after a month (ρ=0,471; p=0.009) and three months after the radiotherapy completion (ρ=0,610; p<0.001). Tapentadol is an opioid analgesic efficient for neuropathy relief in these patients and DN4 questionnaire is an efficient pharmacotherapy tool.

Objective: This study aimed to evaluate pain control, functioning, and quality of life (QoL) recovery in patients with chronic low back pain (cLBP) or post-traumatic osteoarthritis (OA) pain in the ankle/foot area, treated with tapentadol prolonged release and unresponsive to other treatments., Patients and Methods: Two observational retrospective studies were conducted using clinical practice datasets of patients with chronic pain in cLBP and OA foot/ankle at different time points (total follow-up=60-90 days). The studies assessed pain intensity by the Numerical Rating Scale (NRS) pain scale (patients were classified as responder in case of ≥30% pain reduction), QoL by the 5-level EQ-5D (EQ-5D-5L) questionnaire, patient satisfaction by the 7-point Patients' Global Impression of Change (PGIC) scale; cLBP health status by the Roland Morris Disability Questionnaire (RMDQ); foot and ankle functional status by European Foot and Ankle Society (EFAS) score; and treatment-related AEs., Results: For the cLBP setting, 37 patients were enrolled, of which 86.50% were classified as responders (n=32; CI: 75.5% ÷ 97.5%). For the foot/ankle OA pain setting, 21 patients were enrolled. Pain assessment at final follow-up was available only for 11 patients, of which 72.73% (n=8; CI: 39.0% ÷ 94.0%) were classified as responders. Statistically significant improvements were seen in the RMDQ, EQ-5D-5L, and PGIC scores in cLBP. Improvements in the EFAS, EQ-5D-5L, and PGIC scores were seen in OA as well. The incidence of treatment-related adverse reactions was low in both studies., Conclusions: In the study population, tapentadol prolonged release was effective and well tolerated in treating cLBP and post-traumatic foot/ankle OA chronic pain when used in a multimodal manner. The reduction in pain was accompanied by clinically relevant improvements in patients' functionality and QoL.

Tapentadol is a synthetic opioid analgesic with a low risk of abuse and diversion. The rising trend of abuse of tapentadol is largely attributable to its intrinsic pharmacological profile and easy availability due to poor regulatory control. We report a case of intravenous injection of crushed tapentadol tablets that presented with cutaneous adverse drug reactions. Cutaneous adverse reactions are common in injection drug abuse, and clinical examination is a must to inspect the injection sites. Stringent regulatory measures are required to restrict the increasing abuse of tapentadol in India., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Tapentadol is a combined opioid agonist and norepinephrine reuptake inhibitor with fewer gastrointestinal side effects at equianalgesic doses compared with classical strong opioids. Previous studies on tapentadol have included multi-morbid patients in whom confounders exclude detailed assessment of the mechanistic effects and strict comparison with other opioids or placebo. This study aimed at investigating the effects of tapentadol and oxycodone on gastrointestinal motility and gastrointestinal side effects., Methods: 21 healthy males participated in a randomized, double-blind, placebo-controlled, crossover study. Tapentadol (50 mg twice daily), oxycodone (10 mg twice daily), or placebo tablets were administered for 14 days. Segmental gastrointestinal transit times and colonic motility parameters were measured with electromagnetic capsules. Gastrointestinal side effects were assessed using questionnaires., Key Results: During dosing with tapentadol, gastrointestinal side effects and motility parameters were on placebo level. Compared with tapentadol, oxycodone increased whole gut transit time by 17.9 hours (p = .015) and rectosigmoid transit time by 6.5 hours (p = .005). Compared with tapentadol, oxycodone also reduced long, fast antegrade colonic movements (p = .001). In comparison with placebo, oxycodone prolonged whole gut transit time by 31.6 hours, (p < .001). Moreover, less long, fast antegrade colonic movements (p = .002) were observed during oxycodone. For oxycodone only, slow colonic movements were associated with gastrointestinal side effects., Conclusions & Inferences: In this mechanistic study, tapentadol caused significantly less colonic dysmotility and gastrointestinal side effects as compared with oxycodone in equianalgesic doses., (© 2021 John Wiley & Sons Ltd.)

Objective: The present study investigated differences between opioids to experimental tonic pain in healthy men., Methods: Twenty-one males participated in this cross-over-trial. Interventions twice daily were oxycodone (10 mg), tapentadol (50 mg) and placebo for 14 days. Tonic pain was induced on day 1, 4 and 14 by immersing the hand in 2 °C water for 120 s. Electroencephalography was recorded during test pain at baseline and after 14 days. Spectral analysis and source localization were investigated in predefined frequency bands., Results: A decreased perception of pain on day 4 persisted throughout the 14 days compared to baseline (p < 0.006). Oxycodone decreased the electroencephalography spectral power in the delta and theta bands and increased power in the alpha1, alpha2 and beta1 bands (p < 0.03). Tapentadol increased spectral power in the alpha1 band (p < 0.001). Source localization revealed that oxycodone decreased activity of the temporal and limbic region in the delta band, and frontal lobe in the alpha2 and beta1 bands, whereas tapentadol decreased alpha1 band activity in the temporal lobe compared to placebo., Conclusion: Oxycodone and tapentadol reduced pain perception and changed the central processing of tonic pain., Significance: Different mechanisms of action were involved, where oxycodone affected cortical structures more than tapentadol., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

The purpose of this study was to evaluate the antinociceptive interaction between dexketoprofen and tapentadol in three different dose ratios, as well as the ulcerogenic activity of this combination. Dose-response curves were carried out for dexketoprofen, tapentadol, and dexketoprofen-tapentadol combinations in the acetic acid-induced writhing test in mice. On the other hand, the gastric damage of all treatments was assessed after the surgical extraction of the stomachs. Intraperitoneal administration of dexketoprofen and tapentadol induced a dose-dependent antinociceptive effect, reaching a maximal effect of about 58% and 99%, respectively. Isobolographic analysis and the interaction index showed that the three proportions produced an analgesic potentiation (synergistic interaction). Interestingly, the 1:1 and 1:3 ratios of the drugs combination produced minor gastric injury in comparison with the 3:1 proportion. Our data suggest that all proportions of the dexketoprofen-tapentadol combination produced a synergistic interaction in the acetic acid-induced visceral pain model in mice with a low incidence of gastric injury., (© 2020 Société Française de Pharmacologie et de Thérapeutique.)

Recent treatment approaches of osteoarthritis (OA) face a number of obstacles due to the progressive multitude of pain generators, nociceptive mechanisms, first pass mechanism, less efficacy and compromised safety. The present study was aimed to bring a novel approach for the effective management of OA, by developing sublingual targeted nanovesicles (NVs) bearing tapentadol HCl (TAP), surface modified with chondroitin sulfate (CS). Optimized nontargeted nanovesicle formulation (MB-NV) was developed by an ultrasound method, characterized as spherical in shape, nanometric in size (around 150 nm) with narrow size distribution (polydispersity index <0.5), and good entrapment efficiency (around 50%). MB-NV conjugated with CS which was confirmed by IR and 1 H NMR spectroscopy. C-MB-NV showed improved pharmacokinetics parameters i.e. increased t 1/2 (9.7 h), AUC (159.725 μg/mL*h), and MRT (14.99 h) of TAP than nontargeted formulation and plain drug soln. C-MB-NV in in vitro release studies proved sustained drug release pattern for more than 24 h following Higuchi model kinetics with Fickian diffusion ( n  ≤ 0.5).Targeted nanovesicles exhibited an improved bioavailability and enhanced analgesic activity in a disease-induced Wistar rat model which indicated the superior targeting potential of C-MB-NV exploiting CD44 receptors as mediators, overexpressed at the affected joints in the OA model. It could be a propitious approach to accustomed therapies for methodical and efficient management in advanced OA therapy.

Aims: To investigate quality of life (QOL) and functionality changes in chronic pain during tapentadol prolonged release (PR) treatment. Patients & methods: Post hoc analysis of data from three Phase III trials in patients with osteoarthritis knee pain or low back pain. QOL and functionality changes were assessed by SF-36 scores. Results: All SF-36 subdomain scores improved progressively to week 3 of tapentadol titration and were sustained during 12-week maintenance treatment. Improvements in SF-36 scores were similar between tapentadol dose groups (e.g., 200 to <300 mg vs ≥500 mg), with no greater effect from higher doses. QOL and functionality improvements were consistently greater with tapentadol PR than oxycodone controlled release. Conclusion: Tapentadol PR provides consistent, clinically relevant improvements in QOL and functionality in chronic pain.

Purpose of Review: The objective of this systematic review is to present the available evidence for the utilization of the atypical opioids tapentadol, buprenorphine, and levorphanol for the treatment of neuropathic pain., Recent Findings: In total, 1619 articles were retrieved of which 10 studies were included. Of 5 included studies pertaining to tapentadol, 4 studies show tapentadol monotherapy to be effective for the treatment of diabetic peripheral neuropathy or chronic, radiating low back pain. Of the 3 studies included for buprenorphine, only one was a randomized controlled trial found not to have a statistically significant reduction in pain with TD buprenorphine likely due to very high withdrawal rates during the trial. Only 2 case reports were included from the available literature for levorphanol providing low-quality anecdotal evidence. The role of tapentadol, buprenorphine, and levorphanol for neuropathic pain conditions requires robust research including randomized controlled trials to evaluate their efficacy and safety.

Tapentadol has μ-opioid receptor stimulating and noradrenaline reuptake inhibiting properties, and should be effective for neuropathic pain (NP). However, the efficacy of tapentadol for NP in cancer patients is unclear. Ashiya Municipal Hospital (Hyogo, Japan) enrolled five groups of Japanese cancer patients between January 1, 2013, and December 31, 2019. Patients with NP were administered tapentadol (n = 29), methadone (n = 32), oxycodone (n = 20), fentanyl (n = 26), or hydromorphone (n = 20). The primary endpoint was the difference in the verbal rating scale (VRS) scores between days 0 and 7. The secondary endpoint was the tolerability of each opioid. Before administering opioids among the five groups, there was no significant difference in the VRS score (p = 0.99). The mean reduction in the VRS score on day 7 was significantly greater in the tapentadol group than in the oxycodone group (p = 0.0024) and was larger than that of the methadone, fentanyl, and hydromorphone groups. Regarding safety, the discontinuation rate in the tapentadol group was the lowest of all groups (tapentadol vs. methadone vs. oxycodone vs. fentanyl vs. hydromorphone, 0.0% vs. 6.3% vs. 5.0% vs. 3.8% vs. 10.0%, respectively). This study suggests that tapentadol could be efficacious for cancer patients with NP, and a preferred option in cases that require immediate dose adjustment or for those at high risk for adverse effects. However, the pain intensity was evaluated without pain assessment scales specific to NP. Thus, we think that it is desirable to validate our findings using assessment scales, such as the painDETECT questionnaire in future.

Objective: To compare concomitant benzodiazepine (BZDs) use among chronic pain patients adherent to extended-release tapentadol (TapER) or oxycodone (OxnER) and estimate the number of lives potentially saved by switching pa-tients to the less BZD coprescribed treatment., Design: Retrospective database study., Setting: Patients were identified using the IBM MarketScan® Commercial Database. The opioid overdose death esti-mates were obtained from the US national mortality register and were used to estimate the number of lives potentially saved by switching patients to the opioid treatment with lower rates of BZD coprescribing., Patients, Participants: The authors identified 30,213 chronic pain patients between October 2012 and March 2016. Af-ter propensity score matching, N = 2,355 and N = 6,761 patients were adherent (proportion of days covered ≥80 percent) to TapER and OxnER, respectively., Interventions: TapER versus OxnER, during the 180-day treatment., Main Outcome Measure(s): Proportions of BZD coprescribing, BZD dosing patterns in matched patients, and the esti-mated number of lives potentially saved by the opioid treatment switch., Results: TapER patients were less coprescribed BZDs during the treatment period (38.9 percent versus 49.2 percent, OR = 0.659, p < 0.001), and had fewer days of BZD supply per patient (mean: 49.6 versus 70.2 days, p < 0.001) with similar BZD average daily dose. Due to less frequent coprescribing of BZDs with TapER, it is estimated that ~800 deaths may have been avoided in the U.S. as a result of switching patients from OxnER to TapER., Conclusions: Among treatment-adherent patients, TapER patients had fewer BZD coprescriptions than OxnER pa-tients had. Moreover, when BZDs were coprescribed, those BZD prescriptions were for shorter periods of time. Pro-spective studies are warranted to explore rates and consequences of BZD coprescribing among opioids.

Background: Despite the high prevalence of neck pain, few studies have addressed the pharmacological treatment of this condition. Purpose: We evaluated the effectiveness of tapentadol prolonged-release (PR) in patients with or without a neuropathic pain component, with a focus on functional movements, disability and Quality of Life (QoL). Study design/setting: Observational, retrospective study. Patient sample: Ninety-four adult patients with severe neck pain not responsive to opioid step III treatment. Outcome measures: The primary endpoint was a  ≥ 30% improvement of pain intensity at 4 weeks (W4). Several secondary outcomes were evaluated, including neck disability index (NDI), range of motion (ROM), and QoL. Methods: Patients received tapentadol PR at the starting dose of 100 mg/day. Dose titration was allowed in 50 mg increments, up to 500 mg daily. Results: At W4, the primary endpoint of ≥30% improvement of pain was reported in 70% ( n  = 35; 95% confidence interval [CI]: 55-82%) of patients with a neuropathic pain component and in 69% ( n  = 20; 95% CI: 49-85%) of those without a neuropathic component. The percentage of patients reporting a neuropathic pain component significantly decreased from baseline (64.2%) to W4 (27.8%). NDI significantly improved in both groups at W12. ROM significantly improved in all three planes of motion ( p  < .01), with no difference between the two groups. Interference of pain with sleep and QoL also improved. Conclusions: The reduction in pain provided by tapentadol is associated with functional recovery, which may in turn be linked to an improvement in QoL.

Background: Chronic osteoarthritis (OA) pain leads to severe impairments in physical functioning and quality of life. Patients & methods: Data of patients with severe chronic knee and/or hip OA pain were extracted from the database of a prospective, noninterventional trial to assess the benefits of tapentadol prolonged release (PR) in elderly patients (>65 years of age; n = 1162) compared with younger patients (≤65 years of age; n = 498). Results: Tapentadol PR treatment (up to 3 months) significantly reduced pain intensity and pain-related restrictions on daily functioning and significantly improved physical and mental quality of life in both patient groups. The incidence of adverse drug reactions was low. Conclusion: Tapentadol PR is a useful strong analgesic to improve pain intensity, physical functioning and quality of life in elderly OA patients.

Background: Tapentadol is a synthetic opioid analgesic available in India since 2011. International evidence suggests a low risk of abuse and diversion. Our study aims to question this perception in Indian context., Method: We report the trend and profile of Tapentadol abuse cases that were treated at a tertiary level addiction treatment centre in southern India. We also describe the ease of repurposing oral tablets of Tapentadol into an injection. At the national level, we have examined the temporal and spatial trends of online interest in Tapentadol and compared it with a non-opioid drug Ilaprazole and an opioid drug Tramadol using Google Trends. We have used the National Drug Use Survey 2019 to illustrate the regional data., Results: 23 cases of Tapentadol abuse sought treatment between 01/01/2011 and 30/08/2019. In last one year, the number of cases has more than doubled. A majority (N = 19, 83 %) of cases had intravenous Tapentadol abuse, needle sharing and 60 % were diagnosed with Hepatitis C. Tapentadol is attracting new users (N = 13, 56.5 %) as well as replacing other opioids (N = 10, 43.5 %) amongst drug users. Tapentadol has received more online interest than Ilaprazole. Temporal and spatial trends of online interest in Tapentadol parallel Tramadol. States with high prevalence of opioid users have shown high online interest in both opioid drugs., Conclusion: Tapentadol is being widely abused, and urgent regulatory measures are required., Competing Interests: Declaration of Competing Interest None of the authors have any conflict of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Chronic pain is highly prevalent in the elderly, and the prolonged use of long-term opioids for the management of chronic musculoskeletal pain is controversial. Tapentadol, combining μ-opioid receptor (MOR) agonism and noradrenaline reuptake inhibition (NRI) in a unique mechanism of action, may be a valid option for chronic pain management in the geriatric population. The aim of the study was to assess the efficacy and tolerability of tapentadol prolonged release (PR), administered to patients aged ≥ 70 years with chronic pain., Patients and Methods: A total of 20 elderlies, naïve to opioids and with persistent moderate-to-severe chronic pain from different etiologies received tapentadol PR with up-titrations as necessary. The response to treatment, defined as at least 30% reduction in pain intensity compared with baseline, was the primary endpoint. Secondary endpoints were pain intensity on the Numeric Rating Scale (NRS) both at rest and during loading and sleep quality., Results: Tapentadol PR was safe and effective in our population of elderlies with chronic pain from different etiologies: pain intensity compared with baseline, both at rest and during load, was statistically lower at each visit (p<0.01), whereas sleep quality improved significantly throughout the study (p<0.05). Only few minor side effects were reported, with an overall good safety profile and a very high tolerability and satisfaction for treatment., Conclusions: Tapentadol PR, adequately titrated according to patients' response in naïve subjects, is safe and effective to control pain in the elderly.

Musculoskeletal pain, encompassing back and osteoarthritis (OA) pain, represents the most frequent source of chronic pain in western countries, and it is particularly frequent in older adults. Remarkably, back and OA pain present, in most cases, both a nociceptive and a neuropathic component of pain. Treatment selection should, therefore, properly consider the ability of a drug to act on both components, reducing the possibility of plastic changes in the central nervous system, and consequently promoting physical rehabilitation. The pharmacological profile of tapentadol, combining synergistically µ-opioid receptor (MOR) agonist and norepinephrine reuptake inhibition (NRI) in one single molecule with a concomitant reduction in the burden of adverse events, is unique, to date, and makes this drug particularly suitable for the treatment of back pain and OA-associated pain, especially when a neuropathic component is present. Tapentadol is an innovative dual-acting analgesic molecule, which combines two mechanisms of action, namely MOR agonism and NRI. This narrative review will briefly discuss the pharmacological action of tapentadol and its rationale for use in back pain and OA.

Objective: The treatment of chronic pain frequently combines pharmacologic and non-pharmacological options, and analgesia after surgery is of major importance. Tapentadol is both µ-opioid receptor agonist (with a 40% agonism on these receptors) and noradrenaline reuptake inhibitor, with similar analgesic efficacy to strong opioids, but fewer adverse effects. For these reasons, tapentadol may represent a valuable first choice option in the treatment of chronic, neuropathic, and mixed pain., Patients and Methods: The primary endpoint of the present study was the proportion of responder patients, with ≥30% reduction in pain intensity during loading on the NRS; several additional endpoints were also evaluated., Results: Twenty-five adult patients were enrolled, with a rate of response to treatment of 100%. Moreover, pain reduction was as high as 50% in 23/25 patients (92%). The average NRS at rest at V0 was 7.2 ± 1.0, whereas the average NRS at loading was 7.7 ± 0.9; this score significantly decreased at all visits. The score of the Roland-Morris questionnaire, a score of disability, improved significantly throughout the study (p<0.0001), as well as the Barthel Index (p<0.0005), and the neuropathic component of pain, which was significantly reduced during the study, from 88% at V0 to 12% at V3. Sleep quality improved throughout the study, and the treatment was rated as good (91% of patients) or optimal (9%)., Conclusions: Our findings show that tapentadol PR may contribute to improve patients' quality of life, especially during rehabilitation after back surgery, when tapentadol PR treatment is effective and well tolerated.

Objective: Chronic pain is frequently irreversible, representing a major health problem. A survey has shown that 19% of European adults experience chronic pain which is not adequately managed. Innovative interventional techniques for the treatment of chronic pain have been developed, as a further step beyond the three-layer WHO analgesic ladder. Among these techniques, continuous and pulsed radiofrequency (RF) are very effective in the management of radicular pain syndrome. Usually, these techniques are associated with a pharmacologic approach with a wide-spectrum analgesic. Tapentadol has a double mechanism of action, as a μ-opioid receptor agonism (MOR) and noradrenaline reuptake inhibitor (NRI), contributing synergistically to its analgesic efficacy on both nociceptive and neuropathic pain., Patients and Methods: We aimed to test the efficacy of tapentadol prolonged release (PR) combined with pulsed RF in improving neuropathic symptoms and disability in 50 patients with moderate-to-severe chronic pain due to lumbar radiculopathy., Results: The responders to treatment, showing at least a 30% reduction in pain intensity on the Numerical Rating Scale (NRS), were 38 (76%). Both average NRS at rest and during loading were statistically significantly reduced compared with baseline (p<0.0001). Other parameters investigated (sleep quality, neuropathic symptoms, the degree of disability) were all statistically better with tapentadol PR. Patients requiring RF intervention dropped dramatically from 98% at baseline to 10% at the end of the study (p<0.01). Adverse events were reported in 14 patients (28%), four of which required therapy discontinuation. However, patients' satisfaction and overall tolerability of tapentadol PR treatment were high., Conclusions: Tapentadol PR is effective in reducing pain intensity at rest and during loading, with a favorable safety and tolerability profile. Moreover, the use of tapentadol PR decreases the degree and severity of disability, as well as the intensity of neuropathic symptoms.

Objective: The use of long-term opioids for the management of chronic musculoskeletal pain is a hot topic in the scientific community, especially when it concerns the elderly. This paper aimed at assessing the efficacy and tolerability of tapentadol prolonged release (PR), a molecule with a unique mechanism of action combining μ-opioid-receptor (MOR) agonism and noradrenaline reuptake inhibition (NRI), administered to patients aged ≥80 years with chronic persistent pain. The effect of this molecule on anxiety, depression, cognitive status, and overall quality of life were investigated., Patients and Methods: This was a spontaneous, observational, open-label, prospective study, in 80 older patients aged ≥80 years, naïve to strong opioids, presenting moderate-to-severe chronic pain from different etiologies. Tapentadol PR was initially prescribed at the dose of 25-50 mg/day and increased gradually in case of insufficient analgesia. Pain intensity was assessed by a 10-point Numeric Rating Scale (NRS). Other endpoints were as follows: DN4 questionnaire for the evaluation of the neuropathic component of pain, SF12, HADS, and MMSE questionnaires to evaluate the quality of life, anxiety, and cognitive impairment, respectively. Safety evaluations were also performed through the assessment of the frequency and severity of adverse events., Results: At T45, NRS score reduction was achieved in 86.0% of patients. On average, pain decreased by 55% from a mean of 8.2 to a mean of 3.6. At T90, tapentadol PR did not affect the psychophysical and cognitive abilities of older patients., Conclusions: The benefits with tapentadol PR in controlling pain have improved the quality of life of our patients, also showing a favorable effect on their cognitive performance.

We present the case of a 59-year-old woman with third-grade obesity and severe comorbidities including osteoporosis, dyslipidemia, diabetes mellitus, hypertension, night eating following bariatric biliary-intestinal bypass surgery, severe fibromyalgia, poly-arthrosis, lumbar disc herniation in L5S1, sleep disorders and sleep apnea syndrome, and emotional disorders with anxiety and depression, who suffered from chronic pain unresponsive to a combination of multiple analgesics. After a period of metabolic and nutritional rehabilitation, analgesic treatment with tapentadol prolonged release (PR) was started and gradually increased to a daily dose of 300 mg with optimal pain control and a marked improvement in the quality of life and autonomy. Therapy suspension was followed by rebound pain with a worsening in functional capacity, and thus, the patient requested a new rehabilitation treatment, with new benefits. Analgesia is of paramount importance in fragile patients who are undergoing a rehabilitation period, in order to improve compliance with the rehabilitation protocols and increase the success of behavioral therapy. Tapentadol PR can be an effective analgesic therapy for pain control in several settings. Its peculiar tolerability profile improves the acceptability of tapentadol, even in patients with multiple previous analgesic treatments.

Objective: Low back pain (LBP) is a highly prevalent chronic pain condition with a neuropathic component of pain that limits the benefits of classical opioids. Tapentadol is an innovative drug for the treatment of chronic severe pain, with a dual mechanism of action combining µ-opioid receptors agonism and noradrenaline re-uptake inhibition (NRI). Its efficacy is equal to that of strong opioids, with a better tolerability profile and a consequently lower risk of treatment discontinuation. The aim of this study was to evaluate the analgesic efficacy and tolerability of tapentadol prolonged release (PR) vs. other analgesics in patients with moderate-to-severe neuropathic low back pain, before and after back surgery., Patients and Methods: The primary endpoints of the study were the rate of response to treatment, measured as ≥30% reduction in pain intensity on the Numeric Rating Scale (NRS), and tapentadol PR efficacy for pain relief. The secondary endpoints were the improvements of the neuropathic component of pain and of sleep quality., Results: A total of 40 patients were enrolled in the study, receiving either tapentadol PR (n=21, 52.5%) or other analgesics (n=19, 47.5%), both before and after surgery. The rate of response to treatment was statistically in favor of tapentadol PR (p<0.01). The reduction in pain intensity was statistically significant in the group treated with tapentadol PR, both before and after surgery (p<0.01), with a complete resolution of pain 90 days after surgery. The quality of sleep after surgery improved more in patients treated with tapentadol PR than in the comparator group (p<0.01), with 100% of the patients reporting a "good" sleep quality 2 months after surgery., Conclusions: Tapentadol PR was well tolerated by all patients, and its efficacy for pain relief was also confirmed in our small group of "real-life" patients with chronic, severe low back pain. Overall, the tolerability of this treatment may help to improve patients' quality of life, which is frequently compromised because of pain and its related comorbidities.

Background: Tapentadol may allow greater pain relief with reduced "opioid load" compared to oxycodone. Its use has not been studied in the obstetric population. The objective of this study was to compare the efficacy and side effect profile of tapentadol with oxycodone in patients who received spinal anesthesia for elective cesarean section. The trial was registered with EU Clinical Trials Register with CT number 2016-001621-33., Methods: This was a multicenter, randomized controlled trial. Randomized patients (n = 68) received either 50 mg tapentadol or oxycodone 10 mg 12 hourly postoperatively. The primary endpoint was the sum of pain intensity difference over the first 48 hours of treatment (SPID 48 ). Secondary outcomes included time to rescue medications, SPID 36 , total pain relief (TOTPAR) scores, patient satisfaction scores, sum of total pain relief and pain intensity difference (SPRID) scores, time to rescue medications and side effects experienced. An analysis of covariance model with baseline pain intensity score as a covariate was used for statistical analysis., Results: There was no significant difference in the primary endpoint of SPID 48 with adjusted mean difference -11.45 (95% CI -35.35, 12.45) p = .34). Oxycodone showed significantly greater SPID 36 scores compared to tapentadol with increased time to rescue medication. Side effects experienced were similar between groups., Conclusion: Tapentadol did not provide superior pain control or improved tolerability compared to oxycodone post cesarean section. Results should be interpreted however with consideration of administration of intrathecal opioids to all patients in this study and debate over the optimal dose of tapentadol for acute pain.

Introduction: This study compared adverse outcomes and resource use for patients with a diagnosis of pain treated with tapentadol prolonged-release (PR) versus those treated with morphine controlled-release (CR) and oxycodone CR., Methods: Data were sourced from the Clinical Practice Research Datalink (CPRD), a database derived from UK primary care. Patients prescribed tapentadol PR between May 2011 and December 2016 were selected and matched to two groups of controls treated with either morphine CR or oxycodone CR on gender, age, pain duration, pain site, pain aetiology, Charlson index and prior analgesia. Times to first adverse event (constipation or nausea/vomiting) were compared within a Cox proportional hazards model. Rates of primary care contacts, accident and emergency contacts and, for a subset of patients linked to Hospital Episode Statistics (HES), inpatient admissions and outpatient contacts were compared using incidence rate ratios (IRRs) derived from Poisson regression., Results: A total of 1907 patients prescribed tapentadol PR were identified and 1791 (93.9%) had a pain diagnosis. Of these 1246 (65.3%) were matched to morphine controls and 829 (43.4%) to oxycodone controls. Compared to controls, gastrointestinal adverse events with tapentadol PR treatment were reduced; aHR = 0.532 (0.402-0.703; p < 0.001) versus morphine CR and 0.517 (0.363-0.735; p < 0.001) versus oxycodone CR. Compared with morphine CR, primary care contacts [IRR = 0.831 (0.802-0.861)], accident and emergency attendance [0.739 (0.572-0.951)], outpatient contacts [0.917 (0.851-0.989)] and inpatients contacts [0.789 (0.664-0.938)] were reduced. For oxycodone, the respective figures were 0.735 (0.703-0.768), 0.971 (0.699-1.352), 0.877 (0.799-0.962) and 0.748 (0.601-0.932)., Conclusion: Tapentadol PR was associated with significantly fewer adverse gastrointestinal events than morphine CR and oxycodone CR in patients with a diagnosis of pain. There was also significantly reduced primary and secondary care resource use. As with all observational studies, potential bias due to residual confounding and confounding by indication should be considered., Funding: Grünenthal Ltd.

Preclinical Research & Development The purpose of this study was to assess the interaction and mechanisms of action of the paracetamol-tapentadol combination in the formalin-induced pain model in mice. Paracetamol (56.23-562.3 mg/kg, i.p.) or tapentadol (1-10 mg/kg, i.p.) were administered 15 min prior the intraplantar injection of formalin. The ED 50 value of each drug was determined through the dose-response curves. The ED 50 values were used to calculate the combinations in three fixed proportions (1:1, 1:3, and 3:1). Naloxone (1 and 5 mg/kg, i.p.), L-NAME (3 mg/kg, i.p.), or glibenclamide (10 mg/kg, i.p.) were administered before the combination of drugs to evaluate the antinociceptive mechanisms of action. The results showed that the combination 1:1 and paracetamol3-tapenadol1 ratios produced additive effects, whereas the paracetamol1-tapentadol3 proportion showed an antinociceptive synergistic interaction. Moreover, naloxone and glibenclamide reversed the antinociceptive activity of the paracetamol-tapentadol mixture. Our results indicate that the paracetamol-tapentadol combination produces an antinociceptive synergistic interaction with the possible participation of ATP-sensitive K+ channels and μ-opioid receptors in the second phase of the formalin-induced pain model in mice., (© 2018 Wiley Periodicals, Inc.)

Objective: To compare efficacy and safety of tapentadol prolonged release (PR) vs oxycodone controlled release (CR) in younger patients (<65 years of age) and in elderly patients (≥65 and ≥75 years of age) in the treatment of moderate-to-severe chronic osteoarthritis (OA) knee pain., Methods: Data from two double-blind, randomized, placebo-, and oxycodone CR-controlled phase 3 trials were pooled and stratified by age. Primary efficacy end-points were change from baseline in average pain intensity at week 12 (US end-point) and over the entire maintenance period (non-US end-point)., Results: A total of 1357 patients <65 years, 653 patients ≥65 years, and 176 patients ≥75 years of age were assessed. The comparison between tapentadol PR and oxycodone CR showed numerically better pain relief under tapentadol PR for both primary end-points in all three age groups. More favorable improvements were also observed for patient global impression of change, the Short Form-36 physical component score, and EuroQoL-5Dimensions health status index. In the elderly, incidences of dizziness and somnolence were comparable between active treatments, but incidences of nausea, vomiting, and constipation were considerably lower under tapentadol PR. Treatment completion rates were lowest under oxycodone CR; > 50% of elderly oxycodone CR patients named side-effects as the main reason for discontinuation., Conclusions: Tapentadol PR was effective in the treatment of moderate-to-severe chronic OA pain in elderly and younger patients. Compared to oxycodone CR, the overall and the gastrointestinal tolerability profile in particular were better in all tapentadol PR groups, regardless of age.

Tapentadol prolonged release (tapentadol PR) [Palexia ® SR in EU] is a long-acting tablet formulation of the strong central analgesic tapentadol, which acts as both a μ-opioid receptor (MOR) agonist and a noradrenaline reuptake inhibitor. Tapentadol PR is approved for chronic pain in various countries, with its EU indication (severe chronic pain manageable only with opioid analgesics) being the focus here. Well-designed trials and clinical practice data support tapentadol PR use in this setting. Short term, tapentadol PR was an effective and generally well tolerated analgesic for moderate to severe pain of varying aetiologies, including neuropathic pain. It provided analgesia at least as good as that of conventional strong opioids and appeared more favourable in terms of gastrointestinal tolerability, likely due to less potent MOR binding. Severe back pain with a neuropathic component responded well to moderate-dose tapentadol PR in some patients, while for others, an increase to the maximum recommended tapentadol PR dosage provided analgesia at least as good as that of moderate-dose tapentadol PR plus pregabalin and appeared to have some CNS tolerability benefits. Data also support the use of tapentadol PR in opioid rotation, including when conventional opioids are intolerable. Longer-term data in musculoskeletal pain conditions indicate continued benefit over up to 2 years' treatment with tapentadol PR with no evidence of tolerance. Thus, tapentadol PR is a useful option for the management of severe chronic pain.