naloxone and Musculoskeletal-Pain

Chronic pain is a leading cause of disability and represents a relevant societal burden. Opioids are widely used for managing chronic non-cancer pain; however, the high incidence of side effects is often the main reason for discontinuation. Two formulations have recently been studied to improve the tolerability of opioids (tapentadol extended release [ER] and oxycodone/naloxone ER), but a direct comparison between these drugs is not available in the literature. The comparative cost effectiveness of these two drugs has not previously been assessed. The objective of this meta-analysis is a clinical and economic evaluation of tapentadol ER and oxycodone/naloxone ER for the treatment of musculoskeletal pain, by indirect comparison with controlled release (CR) oxycodone.. A structured literature review was conducted to identify published data for the health-economic model. The authors performed a meta-analysis on three selected randomized controlled trials (RCTs) for each treatment (tapentadol ER and oxycodone/naloxone ER). As measure of treatment effect, risk ratio was calculated, compared to the control active treatment (CR oxycodone), for the following outcomes: discontinuation rate due to adverse events, due to gastrointestinal (GE) side effects and central nervous system (CNS) side effects. A Markov model was developed to compare the cost effectiveness of tapentadol ER and oxycodone/naloxone ER. Four health states were defined: (1) patients still on treatment; (2) occurrence of adverse events (gastroenterology, central nervous system); (3) treatment discontinuation as consequence of ineffectiveness of treatment; and (4) treatment discontinuation as consequence of adverse events.. Both drugs showed a significant clinical advantage over the active control, CR oxycodone; however, tapentadol ER resulted in a better risk ratio reduction for the primary outcome of discontinuation rate due to adverse events and for the secondary outcome nausea and vomiting. The two drugs gave equivalent results in the capacity of reduction of constipation risk. In the economic evaluation both interventions were cost effective compared with CR oxycodone. However, tapentadol ER showed the most favorable results as in 65% of cases it was less costly and produced a considerable quality adjusted life years (QALY) gain. The higher impact of tapentadol ER on the cost effectiveness results was probably due to the price and the lower incidence of adverse events and related discontinuation rate, resulting in a further economic advantage.. Both tapentadol ER and oxycodone/naloxone ER are cost effective interventions compared with CR oxycodone; however, tapentadol ER was shown to provide better clinical outcomes at lower costs.

Topics: Chronic Pain; Cost-Benefit Analysis; Delayed-Action Preparations; Humans; Italy; Musculoskeletal Pain; Naloxone; Oxycodone; Phenols; Tapentadol; Treatment Outcome

Current evidence shows that tapentadol hydrochloride prolonged-release is more cost effective than other opioids. However, the introduction into the market of generic formulations of traditional comparators, leading to potential savings due to their lower price, creates space for further research. The objective of this study is to evaluate and compare the efficacy of tapentadol versus oxycodone/naloxone and the economic impact of the two alternatives in both branded and generic formulations.. A cost-effectiveness analysis was performed using the third-payer perspective (TPP), with specific reference to the Italian National Health Service. A Markov model was implemented to simulate transitions between states, comparing two arms: The first arm simulated the administration of tapentadol, while the second simulated the administration of oxycodone/naloxone, both branded and generic. The results were reported in terms of net monetary benefit (NMB). The willingness to pay (WPT) was estimated at €35,000/quality-adjusted life year.. Tapentadol was dominant in all scenarios, assuming a population of 1000 individuals over a 1-year time horizon. In all cases, although the prices of oxycodone/naloxone generic formulations were lower, the costs associated with treatment discontinuation were always higher than those associated with tapentadol. The comparison with the branded formulation of oxycodone/naloxone was associated with the highest savings of €431.77 per patient, and with the highest NMB of €1943.77 per patient.. The results of this pharmacoeconomic evaluation promote the use of tapentadol in comparison with oxycodone/naloxone, confirming the results obtained in previous studies with reference to the generic formulations.

Topics: Analgesics, Opioid; Cost-Benefit Analysis; Delayed-Action Preparations; Humans; Musculoskeletal Pain; Naloxone; Oxycodone; Phenols; State Medicine; Tapentadol

Due to its unclear pathophysiology, the pharmacological treatment of fibromyalgia is a challenge for researchers. Studies using medicinal plants, such as those from the genus Lippia, complexed with cyclodextrins (CDs) have shown innovative results.. The present research intended to evaluate the effect of an inclusion complex containing β-cyclodextrin (βCD) inclusion complex with Lippia grata (LG) essential oil in a chronic musculoskeletal pain model, its central activity and its possible interaction with neurotransmitters involved in pain.. After acid saline-induced chronic muscle pain, male mice were evaluated for primary and secondary hyperalgesia and muscle strength. Moreover, an antagonist assay was performed to assess the possible involvement of the opioidergic, serotonergic and noradrenergic pathways. In addition, Fos protein in the spinal cord was assessed, and a docking study and antioxidant assays were performed.. The treatment with LG-βCD, especially in the dose of 24mg/kg, was able to significantly decrease (p<0.05) the paw withdrawal and muscle threshold. Furthermore, LG-βCD was shown to affect the opioidergic and serotonergic pathways. There were no significant changes in muscle strength. Fos protein immunofluorescence showed a significant decrease in expression in the dorsal horn of the spinal cord. The main compounds of LG showed through the docking study interaction energies with the alpha-adrenergic and μOpioid receptors. In all antioxidant assays, LG exhibited stronger antioxidant activities than LG-βCD.. This study suggested that LG-βCD could be considered as a valuable source for designing new drugs in the treatment of chronic pain, especially musculoskeletal pain.

Topics: Analgesics; Animals; Antioxidants; beta-Cyclodextrins; Chronic Pain; Disease Models, Animal; Hyperalgesia; Lippia; Male; Methysergide; Mice; Molecular Docking Simulation; Musculoskeletal Pain; Naloxone; Oils, Volatile; Plant Leaves; Proto-Oncogene Proteins c-fos; Spinal Cord Dorsal Horn; Yohimbine

Topics: Chronic Pain; Humans; Musculoskeletal Pain; Naloxone; Oxycodone; Phenols

Topics: Chronic Pain; Humans; Musculoskeletal Pain; Naloxone; Oxycodone; Phenols