Quality use of publicly subsidised tapentadol in Australia: a population-based analysis.

BACKGROUND: Sustained-release (SR) tapentadol was listed on Australia's Pharmaceutical Benefits Scheme (PBS) in 2014 for chronic severe pain requiring long-term opioid treatment. Dispensings have increased since listing despite declining trends in other PBS-listed opioids. Preferential prescribing of SR opioids may increase the risk of dependence and accidental overdose, particularly when used to treat acute pain. AIMS: To explore the quality use of publicly subsidised tapentadol in Australia. METHODS: We examined annual initiation rates and patterns of use of tapentadol (SR) in the dispensing records of a 10% random sample of PBS-eligible Australians (2014-2021). We used national tapentadol sales data to assess the proportion of sales attributable to the PBS. RESULTS: Tapentadol initiation increased from 2014, peaking at 7.5/1000 adult population in 2019 before declining to 5.3/1000 in 2021. We identified 63 766 new users between 2014 and 2020, of whom 92.8% discontinued in the first year following initiation, 58.0% had only a single dispensing and 34.3% had no other opioids dispensed in the 3 months before or after initiation. 27.8% of new users were dispensed tapentadol on the same day as potentially interacting medicines. There was a sustained drop in the proportion of sales attributable to the PBS from June 2020 onwards, from an average of 69.1%, to 63.9% of pack sales. CONCLUSIONS: Patterns of use suggest tapentadol (SR) is generally used for short duration. Although most tapentadol sold in Australia is subsidised, there is evidence of a shift towards private sales.

Tapentadol helps in trigeminal neuralgia: a case report.

BACKGROUND: Trigeminal neuralgia (TN) usually affects people over 50 years old. TN-related pains are short-lived, and the disease course is characterized by exacerbations and remissions. Sometimes chronic pain develops due to central sensitization. This is the first case report on the effectiveness of tapentadol in pain control in TN. CASE DESCRIPTION: It is an instructive case history demonstrating the high effectiveness of tapentadol in a 55-year-old Caucasian male with severe [Visual Analogue Scale (VAS) 9/10] TN-related pain and a history of ineffective treatment with antiepileptic drugs. The neuralgia had occurred twice a year for the three preceding years, and typically the TN periods lasted 2-3 weeks with complete remissions between. Previously the patient had been treated with antiepileptic drugs (e.g., carbamazepine, phenytoin, clonazepam, gabapentin, and lamotrigine). However, he found all treatments to be ineffective and accompanied by unacceptable somnolence. Thus, a prolonged-release oral tapentadol was proposed at the beginning of the next relapse. After application of tapentadol, the patient reported a significant improvement. The severity of pain declined to VAS 6/10 (2nd day) and 4/10 (3rd day), and the attacks resolved entirely on the fourth day of treatment. He reported no side effects. The drug was discontinued after 14 days. CONCLUSIONS: Despite pain chronification, tapentadol was efficient and well tolerated in TN. Further research is needed to reveal tapentadol's efficacy in neuralgias.

Comparison of the Effects of OPRM1 A118G Polymorphism Using Different Opioids: A Prospective Study.

CONTEXT: µ-opioid receptor gene (OPRM1) A118G polymorphism (rs1799971) causes loss of N-glycosylation sites at the extracellular domain of µ-opioid receptors. G-allele carriers show a limited response to morphine; however, studies investigating the impact of A118G polymorphism on the efficacy of opioids other than morphine are limited. OBJECTIVE: To compare the impact of A118G polymorphism on the efficacy of various opioids. METHODS: This prospective cohort study enrolled 222 in-patients administered one of the following opioid therapies for cancer pain as part of an opioid introduction or rotation strategy: tapentadol extended-release tablets, methadone tablets, hydromorphone controlled-release tablets, oxycodone controlled-release tablets, or transdermal fentanyl patches. The impact of A118G polymorphism on the difference in the Brief Pain Inventory-Short Form score on days three, seven, and 14 from baseline was compared among the groups. RESULTS: Overall, 81, 74, and 67 patients had the AA, AG, and GG genotypes, respectively, with an OPRM1 A118G G-allele variant frequency of 0.47. The reduction in the Brief Pain Inventory-Short Form score after opioid therapy initiation did not differ significantly among the patients with the three A118G genotypes treated with tapentadol (p = 0.84) or methadone (p = 0.97), whereas it was significantly smaller in G-allele carriers than that in AA homozygous patients treated with hydromorphone (p < 0.001), oxycodone (p = 0.031), or fentanyl (p < 0.001). CONCLUSION: Tapentadol and methadone may be more suitable than hydromorphone, oxycodone, and fentanyl for G-allele carriers due to their dual mechanism of action and low susceptibility to OPRM1 A118G polymorphism.

Tapentadol Immediate Release (IR) versus Morphine Hydrochloride for Postoperative Analgesia of Patients Undergoing Total Abdominal Hysterectomy-A Prospective Cohort Study.

Background and Objectives: This study aimed to examine the efficacy of tapentadol immediate release (IR) and morphine hydrochloride in the treatment of acute postoperative pain after total abdominal hysterectomy, as well as to examine the frequency of opioid-related side effects in observed patients. Materials and Methods: The prospective observational study was conducted over five months, and it included a total number of 100 patients. The two cohorts had different types of postoperative analgesia, and the effects were observed for 24 h postoperatively, by following the pain scores on NRS (Numerical Pain Scale), contentment with analgesia, and opioid-related side effects. Results: Statistical significance was found when assessing pain 24 h after surgery while coughing, where patients in the tapentadol IR group had significantly higher mean pain scores (p < 0.01). The subjective feeling of satisfaction with postoperative analgesia was statistically significant in the tapentadol IR group (p = 0.005). Vertigo appeared significantly more in patients from the morphine group (p = 0.03). Conclusions: Tapentadol IR (immediate release) and morphine hydrochloride are both effective analgesics used in the first 24 h after total transabdominal hysterectomy. Overall satisfaction of patients with analgesia was good. The frequency of side effects was higher in the morphine group, with statistical significance regarding the vertigo.

Cryoneurolysis of alveolar nerves for chronic dental pain: A new technique and a case series.

BACKGROUND: Chronic neuropathic dental pain has a poor prognosis with a low chance of significant spontaneous improvement. Local or oral therapies may be efficient, however short in terms of duration with potential side effects. Cryoneurolysis has been described to prevent acute postoperative pain or to treat some chronic pain conditions; however, application to dental orofacial pain has not been reported so far. CASE SERIES: Following a positive diagnostic block on the corresponding alveolar nerve, neuroablation was performed using a cryoprobe on three patients suffering from persistent pain after a dental extraction and 1 after multiple tooth surgeries. The effect of treatment was assessed using a Pain Numeric Rating Scale (NRS) and determined by changes in medication dosage and quality of life at day 7 and 3 months. Two patients experienced more than 50% of pain relief at 3 months, 2 by 50%. One patient was able to wean off pregabalin medication, one decreased amitriptyline by 50%, and one decreased tapentadol by 50%. No direct complications were reported. All of them mentioned improvement in sleep and quality of life. CONCLUSION: Cryoneurolysis on alveolar nerves is a safe and easy-to-use technique allowing prolonged neuropathic pain relief after dental surgery.

Tapentadol: A Review of Experimental Pharmacology Studies, Clinical Trials, and Recent Findings.

Tapentadol is an analgesic compound that acts centrally to attenuate pain. Previous studies have shown that tapentadol has dual mechanisms of action as a mu-opioid receptor agonist and noradrenaline re-uptake inhibition. Therefore, tapentadol provides a great advantage over classic opioids in pain management from nociceptive to neuropathic. Cumulative evidence from in vitro data suggests that tapentadol effect of norepinephrine re-uptake could be a new target that overcomes other classic opioids in chronic neuropathic pain. Compared to tramadol and other opioids, tapentadol is associated with fewer adverse effects than tramadol. Tapentadol is a new alternative to treat acute, chronic, and neuropathic pain. Thus, this review article was focused on understanding the studies that led to the development of tapentadol as a novel analgesic drug and its advantages over conventional opioids. Thus, tapentadol is a good alternative with fewer adverse effects and is available for human use.

Tapentadol for the management of cancer pain in adults: an update.

PURPOSE OF REVIEW: Tapentadol is the first of a new class of analgesics, having synergistic µ-opioid receptor agonist and noradrenaline reuptake inhibitory actions. It has been widely researched in many areas of pain, often in noninferiority studies against potent opioids. This review describes all randomized and recent nonrandomized studies of tapentadol in adults with cancer pain. RECENT FINDINGS: Tapentadol has been shown to be at least as effective as morphine and oxycodone in five randomized (two of which were multicenter and double-blind) and a range of nonrandomized trials, although caution is needed when interpreting these results. It is effective in both opioid-naive patients and those already taking opioids. By having a lower µ-opioid receptor binding affinity, it has fewer opioid-related toxicities such as constipation and nausea. A recent randomized trial comparing tapentadol to tapentadol plus duloxetine in patients with chemotherapy-induced peripheral neuropathy shows similar improvement in both groups in a range of pain relieving and quality of life measures, with similar adverse effects. SUMMARY: Tapentadol has been shown in a range of studies to be an effective analgesic and thus should be considered as an alternative to morphine and oxycodone, especially when opioid toxicities are an issue.

Appropriate use of tapentadol: focus on the optimal tapering strategy.

OBJECTIVE: Due to its opioid and non-opioid mechanism of action, tapentadol is considered an atypical opioid with improved gastrointestinal tolerability versus traditional opioids. As for all opioid analgesics it is important to understand how to discontinue a treatment when it is not needed anymore. The aim of this article was to provide an overview of opioid therapy in non-cancer pain, with a specific focus on tapering of tapentadol in patients with chronic non-cancer pain, and suggestions on how to achieve tapering. METHODS: Studies for this narrative review were identified via PubMed using a structured search strategy, focusing on management of chronic non-cancer pain with opioids, and the efficacy, tolerability, and pharmacology of tapentadol prolonged release. Publications were limited to English-language articles published within the last ∼10 years. RESULTS: The review discusses the use and discontinuation of opioids in general, as well clinical data on discontinuation of tapentadol specifically. We provide a flow chart, which can be used by clinicians in the context of their own clinical experience to appropriately taper tapentadol in patients with chronic non-cancer pain. The flow chart can be easily tailored to individual patient characteristics, duration of tapentadol treatment, response to progressive dosage reduction, and likelihood of withdrawal symptom occurrence. CONCLUSIONS: While tapentadol is associated with a low frequency of opioid withdrawal symptoms after abrupt discontinuation, use of a tapering strategy is prudent. Tapering strategies developed for opioids in general can potentially be safely individualized in tapentadol-treated patients, although research on tapering strategies for tapentadol is required.

[Tapentadol versus classical WHO-III opioids for chronic back pain. Health services research study based on representative data from health insurance funds]. / Tapentadol versus klassische WHO-III-Opioide bei chronischen Rückenschmerzen : Versorgungsforschungsstudie auf Basis repräsentativer Krankenkassendaten.

BACKGROUND/OBJECTIVE: 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. METHOD: 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. RESULTS: 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). CONCLUSION: 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.

A prospective, multicenter, open-label study of the clinical efficacy of tapentadol extended-release in the treatment of cancer-related pain and improvement in the quality of life of opioid-naïve or opioid-resistant patients.

PURPOSE: This study aimed to investigate the clinical efficacy of tapentadol extended-release (ER) on pain control and the quality of life (QoL) of patients with moderate to severe chronic cancer pain in clinical practice in Korea. METHODS: In this prospective, open-label, multicenter trial, patients with sustained cancer pain as well as chronic pain, who were or were not using other analgesics were enrolled. Thirteen centers recorded a total of 752 patients during the 6-month observation period, based on the tapentadol ER dose and tolerability, prior and concomitant analgesic treatment, pain intensity, type of pain, adverse effects, and clinical global impression change (CGI-C). Of those 752 patients, 688 were enrolled, and 650 completed the study for efficacy and adverse drug reactions; among them, 349 were cancer patients. RESULTS: Tapentadol ER significantly reduced the mean pain intensity including neuropathic pain during the observation period by 2.9 points (from a mean 7 ± 0.87 to 4.1 ± 2.02). Furthermore, QoL was observed to be significantly improved based on the CGI-C, an objective measure. CONCLUSION: This study showed that tapentadol ER was effective for treating patients with moderate to severe cancer pain and neuropathic pain, and therefore it significantly improved the patients' QoL.

Tapentadol and Sleepwalking: A Case Report.

OBJECTIVE: This is a case report of a patient with sleepwalking likely caused by tapentadol ER secondary to higher than the recommended dose for the treatment of pain. METHODS: This report presents the relevant patient history, laboratory data and literature review on possible causes of this patient's sleepwalking. RESULTS: A 39-year-old female reported sleepwalking as the dose of tapentadol increased above the recommended maximum provided in the package insert. The mechanism of action of tapentadol involving norepinephrine reuptake inhibition affecting the central nervous system, higher dosage and drug interactions with other home medications likely contributed to her sleepwalking. CONCLUSION: This case highlights the importance of adhering to the recommended dosage of a medication and if it is clinically warranted to exceed the maximum recommended dose, the importance of diligent monitoring for any adverse effects.

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

Aim: Comparison of tapentadol prolonged 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 using anonymized 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.

Lay abstract Chronic low back pain is a common condition often resulting in impaired functioning in daily life and reduced quality of life and well-being of the patient. In case treatment with less potent pain medications is unsuccessful, opioid treatment might be required. Our study compared the effectiveness and tolerability of the prolonged release formulation of the atypical opioid tapentadol with other strong opioids commonly used for chronic pain treatment in Germany (morphine, hydromorphone, oxycodone ± naloxone). Anonymized patient data from German clinical practices collected in a pain registry were used (2331 comparable patients per treatment group). Patients receiving 12 weeks of tapentadol treatment experienced significantly greater pain relief, greater improvements in daily living activities, sleep, and quality of life compared with those receiving the other strong opioids investigated. Neuropathic pain components (pain features resembling nerve pain, often described as shooting, burning or stabbing pain) were reduced to a greater extent in the tapentadol treatment group. Tapentadol was also significantly better tolerated. This study showed that tapentadol is effective and well tolerated in chronic low back pain treatment in routine medical practice in patients still in considerable pain despite treatment with less potent pain medications.

Tapentadol effects on brain response to pain in sensitized patients with knee osteoarthritis.

OBJECTIVE: Pain sensitization, in the form of knee tenderness and anatomically spread hyperalgesia, is notably common in patients with knee OA and is often refractory to conventional interventions. Tapentadol, as an opioid receptor agonist and noradrenaline reuptake inhibitor, has been proposed as a potentially effective symptomatic treatment for pain-sensitized OA patients. We empirically tested whether tapentadol could attenuate brain response to painful stimulation on the tender knee using functional MRI. METHODS: Painful pressure stimulation was applied to the articular interline and the tibial surface, a commonly sensitized site surrounding the joint. Thirty patients completed the crossover trial designed to compare prolonged release tapentadol and placebo effects administered over 14 days. RESULTS: We found no effects in the direction of the prediction. Instead, patients administered with tapentadol showed stronger activation in response to pressure on the tender site in the right prefrontal cortex and somatosensory cortices. The somatosensory effect was compatible with the spread of neural activation around the knee cortical representation. Consistent with the functional MRI findings, the patients showed higher clinical ratings of pain sensitization under tapentadol and a significant positive association was identified between the number of tapentadol tablets and the evoked subjective pain. CONCLUSION: The tapentadol effect paradoxically involved both the spread of the somatosensory cortex response and a stronger activation in prefrontal areas with a recognized role in the appraisal of pain sensations. Further studies are warranted to explore how OA patients may benefit from powerful analgesic drugs without the associated risks of prolonged use. TRIAL REGISTRATION: EudraCT, https://eudract.ema.europa.eu, 2016-005082-31.

The Treatment of Painful Diabetic Neuropathy.

Painful diabetic peripheral neuropathy (painful-DPN) is a highly prevalent and disabling condition, affecting up to one-third of patients with diabetes. This condition can have a profound impact resulting in a poor quality of life, disruption of employment, impaired sleep, and poor mental health with an excess of depression and anxiety. The management of painful-DPN poses a great challenge. Unfortunately, currently there are no Food and Drug Administration (USA) approved disease-modifying treatments for diabetic peripheral neuropathy (DPN) as trials of putative pathogenetic treatments have failed at phase 3 clinical trial stage. Therefore, the focus of managing painful- DPN other than improving glycaemic control and cardiovascular risk factor modification is treating symptoms. The recommended treatments based on expert international consensus for painful- DPN have remained essentially unchanged for the last decade. Both the serotonin re-uptake inhibitor (SNRI) duloxetine and α2δ ligand pregabalin have the most robust evidence for treating painful-DPN. The weak opioids (e.g. tapentadol and tramadol, both of which have an SNRI effect), tricyclic antidepressants such as amitriptyline and α2δ ligand gabapentin are also widely recommended and prescribed agents. Opioids (except tramadol and tapentadol), should be prescribed with caution in view of the lack of definitive data surrounding efficacy, concerns surrounding addiction and adverse events. Recently, emerging therapies have gained local licenses, including the α2δ ligand mirogabalin (Japan) and the high dose 8% capsaicin patch (FDA and Europe). The management of refractory painful-DPN is difficult; specialist pain services may offer off-label therapies (e.g. botulinum toxin, intravenous lidocaine and spinal cord stimulation), although there is limited clinical trial evidence supporting their use. Additionally, despite combination therapy being commonly used clinically, there is little evidence supporting this practise. There is a need for further clinical trials to assess novel therapeutic agents, optimal combination therapy and existing agents to determine which are the most effective for the treatment of painful-DPN. This article reviews the evidence for the treatment of painful-DPN, including emerging treatment strategies such as novel compounds and stratification of patients according to individual characteristics (e.g. pain phenotype, neuroimaging and genotype) to improve treatment responses.

Comparative study of dezocine, pentazocine and tapentadol on antinociception and physical dependence.

AIMS: Dezocine and pentazocine, widely prescribed in China for postoperative pain, were initially considered as mixed agonist/antagonist targeting µ-opioid receptors (MORs) and κ-opioid receptors (KORs). However, dezocine has been revealed to alleviate chronic neuropathic pain through MOR activation and norepinephrine reuptake inhibition (NRI). This study investigated dezocine- and pentazocine-induced antinociception and physical dependence development, compared to the typical MOR-NRI opioid tapentadol. MAIN METHODS: Calcium mobilization assay was conducted to assess the potency of the drugs while hot-plate test was performed to compare the antinociception. Physical dependence development was compared with morphine. KEY FINDINGS: Treatment with dezocine, pentazocine and tapentadol stimulated calcium mobilization in HEK293 cells stably expressed MORs but not KORs, whereas dezocine and pentazocine inhibited KOR activities. Subcutaneously injected dezocine-, tapentadol- and pentazocine-induced antinociception dose-dependently, in hot-plate test. Intrathecally injected MOR antagonist CTAP, norepinephrine depletor 6-OHDA and α2-adrenoceptor (α2-AR) antagonist yohimbine partially antagonized dezocine, pentazocine and tapentadol antinociception. Whereas specific KOR antagonist GNTI did not alter their antinociception, the putative inverse KOR agonist nor-BNI reduced dezocine and pentazocine antinociception. Moreover, combined CTAP and 6-OHDA or yohimbine blocked dezocine and tapentadol antinociception but displayed the same partial inhibition on pentazocine antinociception as CTAP alone. Furthermore, compared to morphine and pentazocine, long-term treatment with dezocine and tapentadol produced much less physical dependence-related withdrawal signs, which were restored by spinal 6-OHDA or yohimbine treatment. SIGNIFICANCE: Our findings illustrated that dezocine and tapentadol, but not pentazocine, exert remarkable antinociception in nociceptive pain with less abuse liability via dual mechanisms of MOR activation and NRI.

Tapentadol Versus Tramadol: A Narrative and Comparative Review of Their Pharmacological, Efficacy and Safety Profiles in Adult Patients.

We conducted a narrative review of the literature to compare the pharmacological, efficacy and safety profiles of tapentadol and tramadol, and to assess the clinical interest of tapentadol in adult patients. Tapentadol and tramadol share a mixed mechanism of action, including both mu-agonist and monoaminergic properties. Tapentadol is approximately two to three times more potent than tramadol and two to three times less potent than morphine. It has no identified analgesically active metabolite and is not significantly metabolised by cytochrome P450 enzymes, thus overcoming some limitations of tramadol, including the potential for pharmacokinetic drug-drug interactions and interindividual variability due to genetic polymorphisms of cytochrome P450 enzymes. The toxicity profiles of tramadol and tapentadol are similar; however tapentadol is likely to result in less exposure to serotoninergic adverse effects (nausea, vomiting, hypoglycaemia) but cause more opioid adverse effects (constipation, respiratory depression, abuse) than tramadol. The safety of tapentadol in real-world conditions remains poorly documented, particularly in at-risk patient subgroups and also in the ability to assess the risk associated with its residual serotonergic activity (serotonin syndrome, seizures). Because of an earlier market introduction, more real-world safety data are available for tramadol, including data from at-risk patient subgroups. The level of evidence on the efficacy of both tramadol and tapentadol for the treatment of chronic pain is globally low. The trials published to date show overall that tapentadol does not provide a clinically significant analgesic improvement compared to existing treatments, for which the safety profile is much better known. In conclusion, tapentadol is not a first-line opioid but represents an additional analgesic in the therapeutic choices, which some patients may benefit from after careful examination of their clinical situation, co-morbidities and co-medications.

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.

Efficacy and tolerability of tapentadol for the treatment of chronic low back pain in elderly patients.

BACKGROUND: Chronic low back pain (CLBP) is a highly prevalent and disabling condition in the elderly, and yet it is undertreated and understudied in this patient population. Tapentadol is a central analgesic with an improved tolerability profile that may be particularly beneficial to the elderly CLBP. METHODS: We performed an observational retrospective study to comparatively assess the efficacy and tolerability of tapentadol in young and elderly patients with severe CLBP. Sixtyfive young patients (< 65 years) and 87 elderly patients (≥ 65 years) were titrated on tapentadol extended release to their optimal dose (25-250 mg bid) over 1 month and, then, maintained at that dose for 3 months. The primary endpoint were changes from baseline in 24-h pain intensity on a 0-10 Numerical Rating Scale (NRS) at month-4 of treatment (titration plus maintenance periods). Patients were assessed for several efficacy and tolerability outcomes using a battery of scales and tests for neuropathic pain intensity, quality of life and sleep, and cognitive and gastrointestinal functions. RESULTS: At pretreatment, young and elderly patients had similar pain intensities with younger patients presenting with more intense depressive and neuropathic pain symptoms, and lesser comorbidities and durations of pain (P < 0.05). Thirty-eight patients discontinued treatment because of adverse events occurring mostly during titration. Treatment with tapentadol was associated with comparable and clinically meaningful pain reductions in 24-h NRS from baseline to treatment month-4 both in young and elderly patients (- 5.3 ± 1.4 and - 4.8 ± 2.1; P < 0.01); a 50% pain relief was achieved in 66% and 58% of young and elderly patients. The percentage of patients with a neuropathic component decreased similarly in young and elderly patients (from 38 to 0% and from 19 to 3%; P < 0.01). Quality of life and sleep improved. The performances in global cognition and sustained attention tasks remained stable or improved across all age group. CONCLUSIONS: These findings indicate that tapentadol extended release maintains efficacy and good tolerability in CLBP patients with advancing age.

Sublingual delivery of chondroitin sulfate conjugated tapentadol loaded nanovesicles for the treatment of osteoarthritis.

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 1H NMR spectroscopy. C-MB-NV showed improved pharmacokinetics parameters i.e. increased t1/2 (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.

State-of-the-art pharmacotherapy for diabetic neuropathy.

INTRODUCTION: The global epidemic of diabetes has led to an epidemic of diabetes complications. Diabetic neuropathy is the most common microvascular complication, of which diabetic peripheral neuropathy (DPN) and autonomic neuropathy (AN) are the most prevalent, affecting ~50% of patients. DPN results in pain with a poor quality of life and a loss of sensation with an increased risk of foot ulceration. Autonomic neuropathy can cause significant morbidity in a minority and is associated with increased mortality. The cornerstone of treatment to prevent or limit the progression of DPN/AN is multifactorial risk factor modification including treatment of glycemia, lipids and blood pressure. Whilst, there are no FDA-approved disease-modifying therapies, there are a number of therapies to relieve symptoms in DPN and AN. AREAS COVERED: The authors discuss current approved therapies for painful diabetic neuropathy and autonomic neuropathy. They also address the potential role of improving risk factors to limit the development and progression of diabetic neuropathy and new pathogenetic and pain-relieving treatments. EXPERT OPINION: The FDA-approved Pregabalin and Duloxetine over 25 years ago and Tapentadol, 6 years ago for painful diabetic neuropathy. There are currently no FDA-approved disease-modifying treatments for diabetic neuropathy which has been attributed to inappropriate models of the disease with limited translational capacity and major limitations of trial designs and endpoints in clinical trials.