Tapentadol Prolonged Release Research Articles

Pain control and functional recovery as therapeutic goals in patients with chronic musculoskeletal pain: two experiences with tapentadol hydrochloride.

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. 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. 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. 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.

Cost‑Effectiveness Analysis of Tapentadol PR Versus Oxycodone/Naloxone PR in Patients with Musculoskeletal Pain in Spain

Objetive: Chronic musculoskeletal pain is highly prevalent worldwide and is associated with a huge social and economic burden. Opioids are commonly prescribed to treat chronic pain as recommended by the European Pain Federation. Tapentadol prolonged release (PR), is a strong opioid that has proven being effective in treating chronic musculoskeletal pain with less adverse events than oxycodone/naloxone PR. The aim of this study was to estimate the cost-effectiveness of tapentadol PR compared to oxycodone/naloxone PR from the Spanish National Healthcare System perspective (SNHS). Methods: A Markov model was adapted analysing two arms: patients treated with tapentadol PR and patients treated with oxycodone/naloxone PR. The model assesses a cohort of 1,000 patients over a one-year period. Results: Overall, treating patients with tapentadol PR was less costly than treating patients with oxycodone/naloxone PR (€388,631.70 vs €568,168.85). In terms of cost effectiveness, the incremental cost of tapentadol PR over oxycodone/naloxone PR was -€179,537.15 and the incremental quality-adjusted life year value was 40.05. The incremental cost-effectiveness ratio was estimated at -€4,027.16 per quality-adjusted life year suggesting that tapentadol PR is an economically dominant alternative over oxycodone/naloxone PR. Conclusion: Tapentadol PR represents a cost-effective option to treat musculoskeletal chronic pain patients in Spain. Keywords: Musculoskeletal pain, Opioids, Tapentadol PR, Cost effectiveness, Spain.

The role of tapentadol in cancer pain pharmacotherapy in patients with metastatic malignant disease.

The aim of this study was to establish the effects of prolonged formulation of tapentadol in combination with palliative radiotherapy on bone metastatic changes in oncology patients with primary breast cancer and proven bone metastases. The research was conducted as a prospective study at the Clinic for Oncology, University Clinical Center Nis, Nis, Serbia, during a three-month interval of monitoring the patients. The first group comprised 30 patients with mentioned malignancy for which tapentadol was prescribed, and they underwent palliative radiotherapy for bone metastatic changes. The second group comprised 30 patients with the same disease treated only with pain relief radiotherapy to metastatic changes. All the patients were interviewed using the Pain Detect questionnaire. Significantly more patients from the first group had severe pain in comparison to patients from the control group (χ2=16.596; p<0.001) at the second measurement and also at the third measurement (χ2=15.357; p<0.001). At the third measurement, pain with a neuropathic component was significantly more present in patients from the control group (χ2=8.541; p=0.014). There was a significant pain reduction in both groups - Tapentadol group (χ2=59.513; p<0.001) and control group (χ2=60.000; p<0.001) - and also a significant reduction of neuropathic pain component: Tapentadol group (χ2=56.267; p<0.001) and control group (χ2=60,000; p<0.001). There was a statistically significant positive correlation between tapentadol dose and pain intensity according to the numerical pain scale at all three measurements. Tapentadol prolonged-release formulation is an effective pharmacotherapy solution, along with palliative radiotherapy, for pain relief in patients with skeletal metastatic breast cancer. Palliative radiotherapy in these patients does not provide adequate neuropathic pain component relief.

Tapentadol versus klassische WHO-III-Opioide bei chronischen Rückenschmerzen

In clinical trials, tapentadol prolonged release (PR) showed a more favourable gastrointestinal tolerability profile compared to other strong opioids in the treatment of pain. The present analysis compared tapentadol PR and classical WHO-III PR opioids in routine clinical practice. Retrospective cohort study (matched pair approach) using anonymised health insurance data of patients with chronic low back pain who were prescribed strong opioids following pretreatment with WHO-I/II analgesics. Data were analysed from the date of first prescription in 2015 over a maximum period of two years. The primary analysis parameter was the prescription of laxatives. Data of 227 patients per cohort could be included in the analysis. Significantly fewer tapentadol PR than WHO-III PR patients were prescribed laxatives (20.3% vs. 37%; p < 0.0001). In addition, laxative dosages were significantly lower in the tapentadol PR cohort (26.4 vs. 82.5 defined daily doses; p < 0.0001). A significant difference in laxative prescription was also observed under long-term treatment (tapentadol PR patients 27.7% vs. WHO-III PR patients 50%; p = 0.0029). Routine clinical practice indirectly confirmed the more favourable gastrointestinal tolerability of tapentadol PR in the treatment of chronic pain which had previously been demonstrated in clinical trials and non-interventional studies.

Retrospectieve praktijkanalyse van tapentadol met vertraagde afgifte bij patiënten met chronische pijn refractair aan sterke opioïden

Retrospective practice analysis of tapentadol prolonged release in patients with chronic pain refractory to strong opioids Tapentadol is a strong opioid with mixed antinociceptive analgesia and inhibition of the descending pain pathway, tested for the management of different types of chronic refractory pain. In daily practice, tapentadol prolonged release (tapentadol PR) is reserved for patients who already received strong opioids with unsatisfactory pain control or severe side effects, or patients who experienced opioid-induced hyperalgesia. The data of patients treated with tapentadol PR in 3 pain centers in Flanders (Belgium) were analyzed. The primary endpoint was the number of patients who continued the tapentadol PR treatment 6 weeks after it started. The secondary endpoints were pain reduction, global perceived effect (GPE) and side effects. Six weeks after the start of the treatment, 83% of the patients continued the therapy. The median reduction in pain score was 2 points on a numeric scale from 0-10. The GPE showed an improvement of 25% to 30% in 52% of the patients. The mean duration of the tapentadol PR treatment was 6.5 months. Only 24% of the patients stopped the treatment because of side effects and 34% due to an unsatisfactory result. Tapentadol PR is a possible addition in the therapeutic arsenal for the treatment of patients with severe chronic pain.

Tapentadolprolonged release in patients with chronic low back pain: real-world data from the German Pain eRegistry.

Aim: Comparison of tapentadolprolonged release (PR) with other oral WHO-III PR opioid analgesics (morphine, oxycodone±naloxone, hydromorphone) in routine medical care of chronic low back pain. Patients & methods: Noninterventional, retrospective 12-week study usinganonymized clinical practice data from the German Pain eRegistry. Six effectiveness, tolerability, and safety criteria were aggregated in a primary composite end point (treatment responder). Propensity scoring matched 2331 datasets per treatment cohort. Results: All six single criteria showed significantly better outcomes for tapentadol PR (all parameters p<0.001). There were significantly more treatment responders under tapentadol PR (65.7 vs 14.2%; p<0.001). Conclusion: Tapentadol PR showed significantly better effectiveness and tolerability in severe chronic low back pain unsuccessfully treated with WHO-I/II analgesics compared with the other oral WHO-III PR opioids investigated.

Long-Term Effectiveness and Tolerability of Pain Treatment with Tapentadol Prolonged Release

BACKGROUND: The central analgesic tapentadol prolonged release (PR) has proven effective and generally well tolerated in a broad range of chronic pain conditions. Long-term data of its use are still scarce. OBJECTIVES: To evaluate long-term effectiveness, tolerability, and safety of tapentadol PR in patients with severe chronic osteoarthritis (OA) knee pain or low back pain (LBP) who responded to tapentadol in 1 of 4 preceding 12-week phase 3b clinical trials. STUDY DESIGN: Open-label, uncontrolled, observational extension study of up to 72 weeks. SETTING: Fourteen centers in Spain. Protocol approval by the reference ethics committee for all the participating centers. METHODS: Eligible patients started the extension trial on the tapentadol PR dosage optimized for them in the preceding trial; dose adjustments were permitted throughout the extension. Treatment effectiveness outcomes included changes in pain intensity, sleep, state of health, quality of life, patient and clinician global impression of change, and patients’ satisfaction with treatment. Patients with OA knee pain also answered the Western Ontario and McMaster Universities OA index, and patients with LBP with a possible neuropathic pain component completed neuropathic pain-related questionnaires. RESULTS: Eighty-three patients were enrolled: 40 with OA knee pain, 43 with LBP. The full analysis set consisted of 81 patients. Mean pain intensity remained relatively stable over the 72-week extension period with mean increases from baseline of 0.44 (95% confidence interval [CI], -0.1,1.0; Numeric Rating Scale) for all patients, 0.2 (95% CI, -0.5, 0.9) for patients with OA, and 0.68 (95% CI, -0.2, 1.6) for patients with LBP. State of health and quality of life baseline ratings were maintained; overall impression of change was “improved.” Most patients (88.9%) reported at least good treatment satisfaction at the end of treatment. Mean daily tapentadol PR doses slightly increased from 313.3 ± 139.5 mg at baseline to 315.7 ± 140.1 mg at end of study. Uptitration was required for 8.4% of the patients, 4.8% had a dose reduction during the trial. Adverse events considered probably/likely or certainly related to tapentadol PR treatment by the investigator were documented for 18.1% of all patients, most commonly constipation (7.2%). Seven patients (8.4%) experienced adverse events leading to premature discontinuation. LIMITATIONS: An open-label design, stable concomitant analgesics (World Health Organization step I), and dose adjustments were allowed during the study. All patients had benefitted from tapentadol PR in preceding trials. CONCLUSIONS: Sustained pain relief and quality of life for up to 72 treatment weeks under relatively stable dosing, as well as the good safety profile, indicate the usefulness of tapentadol PR for patients who suffer from severe chronic OA knee pain and LBP with limited risk for tolerance development. KEY WORDS: Tapentadol prolonged release, extension study, long-term, chronic pain, osteoarthritis, low back pain, efficacy, safety

Tapentadol Prolonged Release for Long-Term Treatment of Pain in Children.

PurposeInvestigation of the efficacy and safety of tapentadol prolonged release (PR) compared with morphine PR for long-term treatment of pain in children.Patients and MethodsChildren aged 6 to <18 years requiring long-term treatment with opioids were studied in a 12-month, 2-part, multi-center trial: Part 1, 14-day open-label, randomized, active-controlled, parallel group non-inferiority trial comparing twice daily tapentadol PR with morphine PR; Part 2, open-label treatment with tapentadol PR for up to 12 months or no treatment “safety observation period”. Pain intensity was rated with visual analogue scale or Faces Pain Scale-Revised, and non-inferiority was assessed by comparison of “treatment responders” (those completing the 14-day treatment period and showing pre-defined changes in pain rating) in each group.ResultsTwenty-three of 48 centers enrolled 73 patients. In Part 1, 45 and 24 patients received tapentadol or morphine, respectively, of which 40 and 22 completed 14-day treatment. In Part 2, thirty-six and 58 patients entered the tapentadol PR or observation periods, respectively, with 20/36 completing at least 12 weeks of treatment; 10 of the 36 had received morphine in Part 1. Forty-four of the 58 patients in the safety observation period had received tapentadol. Tapentadol PR was non-inferior to morphine PR (lower limit of confidence interval above negative non-inferiority margin of −0.2) in Part 1. Rates of adverse events were as expected with nausea (22.2%) and constipation (15.6%) in the tapentadol PR group, and with vomiting (33.3%), nausea and constipation (each 16.7%) in the morphine PR group. No new safety issues were identified; the safety profile of tapentadol over the 12 months treatment and observation periods was comparable to that established in subjects >18 years old.ConclusionTapentadol PR was well tolerated and equivalent to morphine PR for both efficacy and safety in children (6 to <18 years old) requiring long-term treatment with opioids.

Tapentadol treatment results in long-term pain relief in patients with chronic low back pain and associates with reduced segmental sensitization.

Chronic low back pain (CLBP) is one of the most common chronic pain conditions in pain practice. In the current study, we describe phenotypes of patients with CLBP based on the status of their endogenous pain modulatory system. Conditioned pain modulation (a measure of central pain inhibition), temporal summation (TS, a measure of pain facilitation), and offset analgesia (a measure of temporal filtering of nociception) were evaluated in 53 patients with CLBP at painful and nonpainful sites. Next, in a double-blind, randomized, placebo-controlled trial, 40 patients with defective conditioned pain modulation responses received treatment with tapentadol prolonged-release or placebo for 3 months. The majority of patients (87%) demonstrated loss of central pain inhibition combined with segmentally increased TS and reduced offset analgesia at the lower back region. During treatment, tapentadol reduced pain intensity more than placebo (tapentadol -19.5 ± 2.1 mm versus placebo -7.1 ± 1.8 mm, P = 0.025). Furthermore, tapentadol significantly decreased pain facilitation by reduction of TS responses at the lower back (tapentadol -0.94 ± 1.9 versus placebo 0.01 ± 1.5, P = 0.020), which correlated with pain reduction (P < 0.001). Patients with CLBP demonstrated different phenotypes of endogenous pain modulation. In patients with reduced conditioned pain modulation, tapentadol produced long-term pain relief that coincided with reduction of signs of pain facilitation. These data indicate that the endogenous pain system may be used as a biomarker in the pharmacological treatment of CLBP, enabling an individualized, mechanism-based treatment approach.

Tapentadol Prolonged Release for Severe Chronic Osteoarthritis Pain in the Elderly-A Subgroup Analysis of Routine Clinical Practice Data.

Background Tapentadol prolonged release (PR) has been shown effective and generally well tolerated in a broad range of chronic pain conditions. This subgroup analysis investigated its benefits for elderly patients with severe chronic osteoarthritis (OA) pain in routine clinical practice. Patients and Methods. Data of all patients with chronic OA pain were extracted from the database of a prospective, 3-month noninterventional tapentadol PR trial. The data of elderly OA patients (>65 years of age; n = 752) were compared with the data of younger OA patients (≤65 years; n = 282). Results Almost all patients (elderly 98.7% and younger patients 99.3%) had received long-term analgesic medication prior to the start of tapentadol PR treatment but presented with severe pain accompanied by considerable impairments in sleep quality and quality of life measures. Tapentadol PR provided effective pain relief in both patient groups, with slightly better outcomes in younger patients. However, the mean baseline pain intensity of 7.1 (SD 1.5) was reduced by 3.8 points (p ≤ 0.001), and sleep and quality of life measures had also markedly improved in the elderly: quality of sleep by 3 points, quality of life by 3.4 points, social activities by 3 points, and independence by 2.7 points (p ≤ 0.001 for all measures; 11-point scale). At the end of observation, 68% of the elderly had clinically relevant pain reductions of at least 50% (vs baseline), and 87.9% attained either their intended pain reduction target and/or an additional individual treatment target (both predefined during baseline examination). Only 8.4% of the elderly experienced adverse drug reactions, most frequently nausea (2.7% of patients) and dizziness (1.5%). Conclusion Tapentadol PR provided effective and well-tolerated treatment of severe chronic OA pain for elderly patients in routine clinical practice. The favorable tolerability profile in particular suggests tapentadol PR as a treatment option before classical strong opioids are considered.

Tapentadol prolonged release for managing moderate to severe chronic neck pain with or without a neuropathic component

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.

Tapentadol Prolonged Release for Severe Chronic Osteoarthritis Pain in the Elderly: Improvements in Daily Functioning and Quality of Life

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 (>65years of age; n=1162) compared with younger patients (≤65years of age; n=498). Results: Tapentadol PR treatment (up to 3months) 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.

Efficacy of tapentadol prolonged release for pre- and post-operative low back pain: a prospective observational study.

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. 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. 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. 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.

Tapentadol prolonged release and the long-term management of chronic musculoskeletal pain in the elderly - focus on anxiety, depression, cognitive status and life quality: the TaPE study.

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. 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. 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. 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.

Tapentadol prolonged release in fragile geriatric patients > 70 years with chronic severe musculoskeletal pain: an open-label, prospective, observational study.

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. 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. 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. Tapentadol PR, adequately titrated according to patients' response in naïve subjects, is safe and effective to control pain in the elderly.

Tapentadol prolonged release in association with analgesic radiofrequency for the treatment of chronic lumbar radicular pain: an observational, prospective study.

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. 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. 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. 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.

Tapentadol prolonged release in the treatment of musculoskeletal pain: an innovative pharmacological option.

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.

Efficacy and tolerability of tapentadol prolonged release in the elderly and fragile patient: an observational study.

The incidence of chronic pain increases with age and comorbidities, a particularly relevant issue in the elderly over the age of 80 years. Thus, the choice of the best analgesic treatment is difficult to make. The therapeutic priority in elderly patients is to favor the least invasive route of administration, and the minimum effective dose, with a gradual and slow up-titration, if needed. Tapentadol with its dual mechanism of action, combining synergistically a reduced load (<40% that of strong opioids) of μ-opioid receptor agonism (MOR) with noradrenaline reuptake inhibition (NRI), can be an interesting analgesic option for geriatric patients, because of its easy manageability, the lower rate of adverse effects, the good level of analgesia, and the ability of improving the overall quality of life of elderly patients. A total of 49 elderly patients (>80 years) with chronic pain from different etiologies received tapentadol PR daily over 8 weeks. At the end of the study, responders to treatment were 43% (20/47 patients). Compared with baseline, pain intensity, both at rest and during loading, decreased by 60% and by 55%, respectively (p<0.0001). Tolerability was high throughout the study period, with 92% of patients grading it either good or excellent during follow-up. In total, 16 episodes of side effects were reported, with five considered severe and leading to therapy discontinuation. Ten cases of therapy discontinuation occurred, most of them (five patients, 10%) due to the ineffectiveness of analgesic treatment. Tapentadol PR, adequately titrated according to patients' need, are safe and effective to control pain in most elderly patients.

Efficacy and tolerability of tapentadol prolonged release during rehabilitation: a prospective, observational study.

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. 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. 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%). 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.

Tapentadol in the management of cancer pain: current evidence and future perspectives.

Thanks to the progress in early diagnosis and treatment of cancer, the life expectancy of cancer patients has now increased. Patients are, therefore, more likely to experience their individual cancer pain as a chronic pain. As a consequence, long-term treatment of cancer-related pain and oncological therapy-related pain are a major need for all patients and a challenge to all healthcare professionals. Tapentadol is a centrally acting analgesic drug characterized by two synergistic mechanisms of action, since it acts at the µ-opioid receptor (MOR) and inhibits noradrenalin re-uptake (NRI). Therefore, tapentadol has been considered the first of a new class of drugs, MOR-NRI. Tapentadol has been tested in different populations of cancer patients (opioid-naive and -pretreated), such as those with pain of mixed etiology, patients with pain from hematological malignancies and patients experiencing pain conditions due to anticancer treatment. According to available evidence, tapentadol prolonged release was well tolerated and effective in cancer pain patients. In randomized, double-blind and active-controlled trials it proved non-inferior to standard opioids like morphine or oxycodone in the management of moderate-to-severe cancer pain, both in opioid-naive and in opioid-pretreated patients. The good analgesic efficacy may be partly due to the action of tapentadol on neuropathic pain components. Together with the low rate of gastrointestinal adverse effects and the overall favorable safety profile, tapentadol can be considered a good option in cancer pain patients, who can suffer frequently from nausea, vomiting, constipation or other events that further reduce their quality of life.