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.

Diabetic Neuropathy: A Guide to Pain Management.

PURPOSE OF REVIEW: Diabetic neuropathy is a common complication of diabetes mellitus (DM) and can affect up to 50% of DM patients during their lifetime. Patients typically present with numbness, tingling, pain, and loss of sensation in the extremities. Since there is no treatment targeting the underlying mechanism of neuropathy, strategies focus on preventative care and pain management. RECENT FINDINGS: Up to 69% of patients with diabetic neuropathy receive pharmacological treatment for neuropathic pain. The United States Food and Drug Administration (FDA) confirmed four drugs for painful diabetic neuropathy (PDN): pregabalin, duloxetine, tapentadol, and the 8% capsaicin patch. Nonpharmacological treatments such as spinal cord stimulation (SCS) and transcutaneous electrical nerve stimulation (TENS) both show promise in reducing pain in DM patients. Despite the high burden associated with PDN, effective management remains challenging. This update covers the background and management of diabetic neuropathy, including its epidemiology, pathogenesis, preventative care, and current therapeutic strategies.

Pharmacokinetics of oral tapentadol in cats.

To evaluate pharmacokinetics of one dose of tapentadol hydrochloride orally administered to cats. Prospective experimental study. Five healthy adult mixed-breed cats. Each cat received 18.8 ± 1.0 mg/kg tapentadol orally. Venous blood samples were collected at time 0 (immediately prior to administration of tapentadol) 1, 2, 5, 10, 15, 30, 45, 60, 90 min, and 2, 4, 8, 12 to 24 h after drug administration. Plasma tapentadol concentrations and its metabolites were determined using ultra-performance liquid chromatography-tandem mass spectrometry. Geometric mean Tmax of tapentadol, desmethyltapentadol, tapentadol-O-glucuronide, and tapentadol-O-sulfate was 2.3, 7.0, 6.0, and 4.6 h, respectively. Mean Cmax of tapentadol, desmethyltapentadol, tapentadol-O-glucuronide, and tapentadol-O-sulfate was 637, 66, 1134, and 15,757 ng/mL, respectively, after administration. Mean half-life of tapentadol, desmethyltapentadol, tapentadol-O-glucuronide, and tapentadol-O-sulfate was 2.4, 4.7, 2.9, and 10.8 h. The relative exposure of tapentadol and its metabolites were tapentadol 2.65%, desmethyltapentadol 0.54%, tapentadol-O-glucuronide 6.22%, and tapentadol-O-sulfate 90.6%. Tapentadol-O-sulfate was the predominant metabolite following the administration of oral tapentadol in cats. Further studies are warranted to evaluate the association of analgesia with plasma concentrations of tapentadol.

Direct, Stereodivergent, and Catalytic Michael Additions of Thioimides to α,ß-Unsaturated Aldehydes - Total Synthesis of Tapentadol.

Direct and stereodivergent Michael additions of N-acyl 1,3-thiazinane-2-thiones to α,ß-unsaturated aldehydes catalyzed by chiral nickel(II) complexes are reported. The reactions proceed with a remarkable regio-, diastereo-, and enantioselectivity, so access to any of the four potential Michael stereoisomers is granted through the appropriate choice of the chiral ligand of the nickel(II) complex. Simple removal of the heterocyclic scaffold furnishes a wide array of either syn or anti enantiomerically pure derivatives, which can be exploited for the asymmetric synthesis of biologically active compounds, as demonstrated in a new approach to tapentadol. In turn, a mechanism, based on theoretical calculations, is proposed to account for the stereochemical outcome of these transformations.

Effect of discharge opioid on persistent postoperative opioid use: a retrospective cohort study comparing tapentadol with oxycodone.

Opioid harm can vary by opioid type. This observational study examined the effect of opioid type (oxycodone vs. tapentadol) on rates of persistent postoperative opioid use ('persistence'). We linked hospital and community pharmacy data for surgical patients who were dispensed discharge opioids between 1 January 2016 and 30 September 2021. Patients were grouped by opioid experience ('opioid-naive' having received no opioids in the 3 months before discharge) and formulation of discharge opioid (immediate release only or modified release ± immediate release). Mixed-effects logistic regression models predicted persistence (continued use of any opioid at 90 days after discharge), controlling for key persistence risk factors. Of the 122,836 patients, 2.31% opioid-naive and 27.24% opioid-experienced patients met the criteria for persistence. For opioid-naive patients receiving immediate release opioids, there was no significant effect of opioid type. Tapentadol modified release was associated with significantly lower odds of persistence compared with oxycodone modified release, OR (95%CI) 0.81 (0.69-0.94) for opioid-naive patients and 0.81 (0.71-0.93) for opioid-experienced patients. Among patients who underwent orthopaedic surgery (n = 19,832), regardless of opioid experience or opioid formulation, the odds of persistence were significantly lower for those who received tapentadol compared with oxycodone. This was one of the largest and most extensive studies of persistent postoperative opioid use, and the first that specifically examined persistence with tapentadol. There appeared to be lower odds of persistence for tapentadol compared with oxycodone among key subgroups, including patients prescribed modified release opioids and those undergoing orthopaedic surgery.

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.

Novel Natrosol/Pectin-co-poly (acrylate) based pH-responsive polymeric carrier system for controlled delivery of Tapentadol Hydrochloride.

Background & Objectives: This study aimed to create a controlled delivery system for Tapentadol Hydrochloride by developing interpenetrating networks (IPNs) of Natrosol-Pectin copolymerized with Acrylic Acid and Methylene bisacrylamide, and to analyze the effects of various ingredients on the physical and chemical characteristics of the IPNs. Methods: Novel Tapentadol Hydrochloride-loaded Natrosol-Pectin based IPNs were formulated by using the free radical polymerization technique. Co-polymerization of Acrylic Acid (AA) with Natrosol and Pectin was performed by using Methylene bisacrylamide (MBA). Ammonium persulfate (APS) was used as the initiator of crosslinking process. The impact of ingredients i.e. Natrosol, Pectin, MBA, and Acrylic Acid on the gel fraction, porosity, swelling (%), drug loading, and drug release was investigated. FTIR, DSC, TGA, SEM and EDX studies were conducted to confirm the grafting of polymers and to evaluate the thermal stability and surface morphology of the developed IPNs. Results: Swelling studies exhibited an increase in swelling percentage from 84.27 to 91.17% upon increasing polymer (Natrosol and Pectin) contents. An increase in MBA contents resulted in a decrease in swelling from 85 to 67.63%. Moreover, the swelling was also observed to increase with higher AA contents. Significant drug release was noted at higher pH instead of gastric pH value. Oral toxicological studies revealed the nontoxic and biocompatible nature of Natrosol-Pectin IPNs. Interpretation & Conclusion: The developed IPNs were found to be an excellent system for the controlled delivery of Tapentadol Hydrochloride.

Tapentadol and oxycodone reduce cingulate glutamate in healthy volunteers.

Tapentadol and oxycodone are commonly used analgesics. Preclinical studies have shown that oxycodone modulates brain metabolites related to opioid pathways, whereas tapentadol also affects noradrenergic activity. However, knowledge about the function of the medications in the human brain is limited. The aim was to investigate effects of tapentadol and oxycodone on brain glutamate, the most important neurotransmitter in pain processing. Magnetic resonance spectroscopy was obtained in 21 healthy subjects from the anterior cingulate cortex, prefrontal cortex, and insula at baseline and after 14 days of treatment with either 50 mg tapentadol, 10 mg oxycodone (equipotent dose, both extended release) or placebo twice daily in a randomized double-blind cross-over study. Compared to baseline, decreased glutamate/creatine levels were identified in anterior cingulate cortex after tapentadol (1.26 ± 0.14 vs. 1.35 ± 0.18, P = .04) and oxycodone (1.26 ± 0.10 vs. 1.35 ± 0.12, P = .05) treatments, both with 7% reduction. This indicates that both analgesics modulate the glutamatergic system at the supraspinal level in humans.

Prescribing trend of tapentadol in a Sydney local health district.

AIMS: Tapentadol, an opioid with mu-opioid receptor agonism and noradrenaline reuptake inhibition, has been increasingly used in Australia since 2011. However, data on hospital prescribing trends and indications are scarce. This study aimed to investigate hospital prescribing trends of tapentadol, oxycodone and tramadol in a Sydney local health district (LHD) and the indications for tapentadol hospital prescriptions in an Australian tertiary hospital. METHODS: We analysed 5-year patient dispensing for tapentadol, oxycodone and tramadol from four hospitals in a Sydney LHD with data expressed as oral morphine equivalents (OME). We also conducted a retrospective review of 140 and 54 patients prescribed tapentadol at a tertiary hospital's surgical and spinal units in 2020. RESULTS: Over 5 years in the Sydney LHD, there was a 19.5% reduction in total dispensing of these opioids from 1 225 210 to 986 477.5 OME milligrams. Decreases were specifically for oxycodone (-37.8% immediate-release, -65.2% sustained-release) and tramadol (-74.6% immediate-release, -70.1% sustained-release). Contrastingly, hospital prescriptions of tapentadol immediate-release increased by 223.2% between 2018-19 and 2020-21 while sustained-release increased by 17.9% from 2016-17 to 2020-21. By 2020-21, tapentadol overtook oxycodone to become the most prescribed opioid in the Sydney LHD (51.4%). At the hospital's surgical units, 137 (97.9%) patients were prescribed tapentadol for acute post-operative pain with the majority (54.0%) prescribed both immediate-release and sustained-release tapentadol, while 71.1% were prescribed for neuropathic pain in the spinal units. CONCLUSION: In a Sydney LHD, tapentadol prescriptions increased significantly to become the preferred opioid analgesic. At the hospital's surgical units, off-label prescriptions of tapentadol sustained-release for acute post-operative pain were observed.

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.

Effects of Different Opioid Drugs on Oxidative Status and Proteasome Activity in SH-SY5Y Cells.

Opioids are the most effective drugs used for the management of moderate to severe pain; however, their chronic use is often associated with numerous adverse effects. Some results indicate the involvement of oxidative stress as well as of proteasome function in the development of some opioid-related side effects including analgesic tolerance, opioid-induced hyperalgesia (OIH) and dependence. Based on the evidence, this study investigated the impact of morphine, buprenorphine or tapentadol on intracellular reactive oxygen species levels (ROS), superoxide dismutase activity/gene expression, as well as ß2 and ß5 subunit proteasome activity/biosynthesis in SH-SY5Y cells. Results showed that tested opioids differently altered ROS production and SOD activity/biosynthesis. Indeed, the increase in ROS production and the reduction in SOD function elicited by morphine were not shared by the other opioids. Moreover, tested drugs produced distinct changes in ß2(trypsin-like) and ß5(chymotrypsin-like) proteasome activity and biosynthesis. In fact, while prolonged morphine exposure significantly increased the proteolytic activity of both subunits and ß5 mRNA levels, buprenorphine and tapentadol either reduced or did not alter these parameters. These results, showing different actions of the selected opioid drugs on the investigated parameters, suggest that a low µ receptor intrinsic efficacy could be related to a smaller oxidative stress and proteasome activation and could be useful to shed more light on the role of the investigated cellular processes in the occurrence of these opioid drug side effects.

Tapentadol, Buprenorphine, and Levorphanol for the Treatment of Neuropathic Pain: a Systematic Review.

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.

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.

Pilot Study of a Single Dose of Orally Administered Tapentadol Suspension in Hispaniolan Amazon Parrots (Amazona ventralis).

Tapentadol is an analgesic agent that acts as both a µ-opioid receptor agonist and a norepinephrine reuptake inhibitor. It is a common therapeutic agent in human medicine for management of acute and chronic pain, and it is currently being investigated for use in veterinary medicine. Tapentadol was evaluated in Hispaniolan Amazon parrots (Amazona ventralis) because there is only 1 other oral opioid-like analgesic agent, tramadol, which has been evaluated in an avian species. The effectiveness of tramadol after administration to a patient involves a complex physiologic metabolism and has been found to have variable pharmacokinetics between species. Because of the lack of active metabolites from tapentadol, less interspecific variation was expected. Seven Hispaniolan Amazon parrots were used to evaluate the pharmacokinetics of tapentadol after a single 30 mg/kg PO administration of a compounded 5 mg/mL tapentadol suspension. Blood samples were collected before (time 0) and 0.25, 0.5, 0.75, 1, 1.5, 3, and 6 hours after administration, following a balanced, incomplete-block design. Plasma tapentadol concentrations were measured by high-pressure liquid chromatography with mass spectrometry. Results revealed detectable plasma concentrations in only 2 of 7 birds (29%), and the bird with the highest plasma levels had a peak concentration (Cmax) of 143 ng/mL and a half-life (T 1/2) of 24.8 minutes. The variable plasma concentrations and short half-life of this drug in Hispaniolan Amazon parrots suggests that this drug would be of limited clinical use in this species; however, it is possible that this drug will be more bioavailable in other avian species.

Opioid receptors beyond pain control: The role in cancer pathology and the debated importance of their pharmacological modulation.

Stimulation of opioid receptors is widely used for relieving cancer pain in patients with advanced cancer. The expression of tissue opioid receptors varies depending on the types of cancer and it is regulated by several factors. This review provides a focused overview of the current evidence for the role of opioid receptors in modulating cancer progression, a discussion of the proposed underlying mechanisms and the pharmacological activity of opioid agonists and antagonists. Conflicting evidence from preclinical and clinical studies suggests the possible involvement of opioid receptor agonists in both the development and suppression of human cancer. Some retrospective clinical studies also show a possible detrimental effect on long-term patient outcomes. Among the opioid receptor agonists, morphine has been extensively studied in various cancer types. Moreover, various pathological processes of human cancer are affected by opioid receptor agonists, such as tumour growth, angiogenesis and immunosuppression. These findings highlight the functional value of opioid receptors in human cancer, and a potential double role of opioid receptor agonists and antagonists in human cancer treatment.

Evaluation of Abuse and Route of Administration of Extended-Release Tapentadol Among Treatment-Seeking Individuals, as Captured by the Addiction Severity Index-Multimedia Version (ASI-MV).

BACKGROUND: Tapentadol is a molecule incorporating mu opioid receptor agonism and norepinephrine reuptake inhibition to provide analgesia, with the potential for a lower incidence of gastrointestinal side effects than full mu opioid agonists. Postmarketing surveillance of tapentadol as an active pharmaceutical ingredient has consistently revealed low levels of abuse and diversion. OBJECTIVE: The purpose of the present study was to further characterize the abuse liability of tapentadol extended-release (ER) by evaluating the prevalence of past 30-day tapentadol ER abuse and reported routes of administration as compared with ER opioids with Food and Drug Administration (FDA) abuse-deterrent labeling ("ADF opioids") and ER opioids without FDA abuse-deterrent labeling ("non-ADF opioids"). METHODS: Data were collected from January 2014 through December 2017 from 776 centers located in 43 states throughout the United States using the Addiction Severity Index-Multimedia Version (ASI-MV), an instrument that is integral to the National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO, Inflexxion, an IBH Company, Costa Mesa, CA, USA). RESULTS: Tapentadol ER had lower rates of past 30-day abuse than ADF ER and non-ADF ER opioid comparators, both at a population level and when adjusted for drug utilization. Tapentadol ER was primarily abused orally, although it was also abused through alternate routes of administration. Cumulative rates of tapentadol ER abuse by alternative routes of administration were lower than both ADF and non-ADF ER opioid comparators, although large confidence intervals resulting from the small sample size of reported tapentadol ER use limit firm conclusions. CONCLUSIONS: In summary, tapentadol ER was found to have lower rates of both past 30-day abuse and use via alternate routes of administration, specifically snorting and smoking, than ADF and non-ADF ER comparators.

Pharmacokinetic Analysis, Analgesic Effects, and Adverse Effects of Tapentadol in Cancer Patients with Pain.

In this study, we conducted a pharmacokinetic analysis of tapentadol (TP) in Japanese patients with cancer pain and identified covariates influencing pharmacokinetic parameters. In addition, the analgesic effects and adverse effects of TP were investigated. Data were collected from in-patients with cancer pain who had been administered TP as an extended-release formula. The median (range) estimated clearance (CL/F) and distribution volume (Vd/F) of TP were 86.7 (31.3-213.7) L/h and 1288 (189-6736) L, respectively. There was a strong negative correlation between CL/F and age, Child-Pugh score, and albumin-bilirubin (ALBI) score. The subjects were further divided into two groups according to the factors highly correlated with CL/F. The CL/F of patients in the Child-Pugh B group was 0.46-times that of patients in the Child-Pugh A group. In addition, the CL/F of patients with an ALBI score > -2.40 was 0.56-times that of patients with ALBI scores ≤-2.40, and both differences were statistically significant (p < 0.05). The mean intensity of pain over 24 h was investigated daily from before starting TP for the first 7 d of the treatment. TP reduced pain in six of nine patients; the mean pain visual analogue scale score decreased significantly from 59.2 mm before administration to 42.5 mm at days 5-7. Overall, the Child-Pugh and ALBI scores significantly affected the clearance of TP, which was reduced in patients with impaired liver function. These results suggest that TP is an opioid with a sufficient analgesic effect for cancer patients.

Tapentadol Suppresses Glutamatergic Transmission and Neuronal Firing in Rat Hippocampal CA3 Pyramidal Neurons.

BACKGROUND: Tapentadol, a centrally acting oral analgesic, activates µ-opioid receptor and inhibits norepinephrine reuptake. Given that glutamate plays a crucial role in mediating pain, this study investigated the influence of tapentadol on spontaneous glutamatergic synaptic transmission and evoked neuronal excitability in rat hippocampal CA3 pyramidal neurons, which has been suggested to be involved in nociceptive perception. METHODS: We used electrophysiological technique to determine the effect of tapentadol on spontaneous excitatory postsynaptic currents (sEPSC), glutamate-activated currents, and neuronal excitability in CA3 pyramidal neurons in rat hippocampal slices. We also used isolated nerve terminals (synaptosomes) prepared from the rat hippocampus to examine the effect of tapentadol on glutamate release. RESULTS: Whole-cell patch clamp recordings revealed that tapentadol effectively decreased the frequencies of sEPSCs and miniature EPSCs (mEPSCs) without changing their amplitudes in hippocampal CA3 pyramidal neurons. However, glutamate-evoked inward currents were not affected by tapentadol. Further, tapentadol decreased 4-aminopyridine-induced glutamate release from hippocampal synaptosomes, and this effect was prevented by chelating the extracellular Ca2+ ions and blocking the N- and P/Q-type Ca2+ channels. In addition, burst firing induced by 4-aminopyridine and tonic repetitive firing induced by depolarizing pulses were attenuated by tapentadol. CONCLUSIONS: We conclude that tapentadol inhibits glutamatergic synaptic transmission, without modifying postsynaptic receptor sensitivity, and that this decline of excitation consequently suppresses neuronal hyperexcitability in the hippocampal CA3 area.

Tapentadol is effective in the management of moderate-to-severe cancer-related pain in opioid-naïve and opioid-tolerant patients: a retrospective study.

PURPOSE: Tapentadol is a dual-acting mu-opioid receptor agonist and noradrenaline reuptake inhibitor with non-inferior analgesic efficacy to oxycodone and better gastrointestinal tolerability than full mu-opioid receptor agonists. Tapentadol is approved for cancer pain in Japan; however, real-world evidence on tapentadol's effectiveness and safety for cancer-related pain in Japan is limited. METHODS: This retrospective study evaluated the effectiveness, safety, and tolerability of tapentadol (by patient type-opioid-naïve and opioid-tolerant) in 84 patients with moderate-to-severe cancer pain at Ichikawa General Hospital between September 2014 and August 2016. RESULTS: Almost 93% of patients achieved clinically relevant pain relief within 4 days (median). Over 90% of patients with neuropathic pain or mixed pain and all patients with nociceptive pain were responders. Pain intensity significantly decreased from baseline through to the end of maintenance period in opioid-naïve and opioid-tolerant patients. No patients discontinued tapentadol due to serious adverse events. No opioid-naïve patients experienced nausea or vomiting during tapentadol treatment. Only three opioid-tolerant patients experienced nausea which was considered to be related to tapentadol. CONCLUSION: Tapentadol is effective and well tolerated in opioid-naïve and opioid-tolerant patients with cancer pain of varying pathophysiology, including those with nociceptive and/or neuropathic components. Tapentadol may be considered for first-line use in moderate-to-severe cancer-related pain.