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Background: Oliceridine is a novel G protein-biased ligand µ-opioid receptor agonist. This study aimed to assess the pharmacokinetics and safety profile of single-ascending doses of oliceridine fumarate injection in Chinese patients with chronic non-cancer pain. Methods: Conducted as a single-center, open-label trial, this study administered single doses of 0.75, 1.5, and 3.0 mg to 32 adult participants. The trial was conducted in two parts. First, we conducted a preliminary test comprising the administration of a single dose of 0.75mg to 2 participants. Then, we conducted the main trial involving intravenous administration of escalating doses of oliceridine fumarate (0.75 to 3 mg) to 30 participants. Pharmacokinetic (PK) parameters were derived using non-compartmental analysis. Additionally, the safety evaluation encompassed the monitoring of adverse events (AEs). Results: 32 participants were included in the PK and safety analyses. Following a 2-min intravenous infusion of oliceridine fumarate injection (0.75, 1.5, or 3 mg), Cmax and Tmax ranged from 51.293 to 81.914 ng/mL and 0.034 to 0.083 h, respectively. AUC0-t and half-life (t1/2) increased more than proportionally with dosage (1.85-2.084 h). Treatment emergent adverse events (TEAEs) were found to be consistent with the commonly reported adverse effects of opioids, both post-administration and as documented in the original trials conducted in the United States. Critically, no serious adverse events were observed. Conclusion: Oliceridine demonstrated comparable PK parameters and a consistent PK profile in the Chinese population, in line with the PK results observed in the original trials conducted in the United States. Oliceridine was safe and well tolerated in Chinese patients with chronic non-cancer pain at doses ranging from 0.75 mg to 3.0 mg. Trial Registration: The trial is registered at chictr.org.cn (ChiCTR2100047180).
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Dolor Crónico , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Adulto , Femenino , Dolor Crónico/tratamiento farmacológico , Persona de Mediana Edad , Adulto Joven , Pueblo Asiatico , China , Pueblos del Este de Asia , Compuestos de Espiro , TiofenosRESUMEN
Background: In the absence of head-to-head comparative data from randomized controlled trials, indirect treatment comparisons (ITCs) may be used to compare the relative effects of treatments versus a common comparator (either placebo or active treatment). For acute pain management, the effects of oliceridine have been compared in clinical trials to morphine but not to fentanyl or hydromorphone. Aim: To assess the comparative safety (specifically differences in the incidence of nausea, vomiting and opioid-induced respiratory depression [OIRD]) between oliceridine and relevant comparators (fentanyl and hydromorphone) through ITC analysis. Methods: A systematic literature review identified randomized clinical trials with oliceridine versus morphine and morphine versus fentanyl or hydromorphone. The ITC utilized the common active comparator, morphine, for the analysis. Results: A total of six randomized controlled trials (oliceridine - 2; hydromorphone - 3; fentanyl - 1) were identified for data to be used in the ITC analyses. The oliceridine data were reported in two studies (plastic surgery and orthopedic surgery) and were also reported in a pooled analysis. The ITC focused on nausea and vomiting due to limited data for OIRD. When oliceridine was compared with hydromorphone in the ITC analysis, oliceridine significantly reduced the incidence of nausea and/or vomiting requiring antiemetics compared with hydromorphone (both orthopedic surgery and pooled data), while results in plastic surgery were not statistically significant. When oliceridine was compared with hydromorphone utilizing data from Hong, the ITC only showed a trend toward reduced risk of nausea and vomiting with oliceridine that was not statistically significant across all three comparisons (orthopedic surgery, plastic surgery and combined). An ITC comparing oliceridine with a study of fentanyl utilizing the oliceridine orthopedic surgery data and combined orthopedic and plastic surgery data showed a trend toward reduced risk that was not statistically significant. Conclusion: In ITC analyses, oliceridine significantly reduced the incidence of nausea and/or vomiting or the need for antiemetics in orthopedic surgery compared with hydromorphone and a non-significant trend toward reduced risk versus fentanyl.
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Dolor Agudo , Analgésicos Opioides , Fentanilo , Hidromorfona , Náusea , Ensayos Clínicos Controlados Aleatorios como Asunto , Compuestos de Espiro , Tiofenos , Vómitos , Humanos , Hidromorfona/administración & dosificación , Hidromorfona/efectos adversos , Hidromorfona/uso terapéutico , Fentanilo/efectos adversos , Fentanilo/administración & dosificación , Fentanilo/uso terapéutico , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/uso terapéutico , Analgésicos Opioides/administración & dosificación , Dolor Agudo/tratamiento farmacológico , Vómitos/inducido químicamente , Vómitos/prevención & control , Vómitos/tratamiento farmacológico , Náusea/prevención & control , Náusea/inducido químicamente , Náusea/tratamiento farmacológico , Administración Intravenosa , Insuficiencia Respiratoria/inducido químicamente , Manejo del Dolor/métodos , Quinuclidinas/uso terapéutico , Quinuclidinas/administración & dosificación , Quinuclidinas/efectos adversosRESUMEN
Opioid analgesics such as morphine and fentanyl induce mu-opioid receptor (MOR)-mediated hyperactivity in mice. Herein, we show that morphine, fentanyl, SR-17018, and oliceridine have submaximal intrinsic efficacy in the mouse striatum using 35S-GTPγS binding assays. While all of the agonists act as partial agonists for stimulating G protein coupling in striatum, morphine, fentanyl, and oliceridine are fully efficacious in stimulating locomotor activity; meanwhile, the noncompetitive biased agonists SR-17018 and SR-15099 produce submaximal hyperactivity. Moreover, the combination of SR-17018 and morphine attenuates hyperactivity while antinociceptive efficacy is increased. The combination of oliceridine with morphine increases hyperactivity, which is maintained over time. These findings provide evidence that noncompetitive agonists at MOR can be used to suppress morphine-induced hyperactivity while enhancing antinociceptive efficacy; moreover, they demonstrate that intrinsic efficacy measured at the receptor level is not directly proportional to drug efficacy in the locomotor activity assay.
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Morfina , Compuestos de Espiro , Ratones , Animales , Morfina/farmacología , Analgésicos Opioides/farmacología , Fentanilo/farmacologíaRESUMEN
AIM: Our aim was to conduct a systematic review and meta-analysis to examine the efficacy and safety of oliceridine in patients with postoperative pain. METHODS: Four databases were searched from the beginning of the database to the present. We included all randomized controlled trials (RCT) that evaluated the efficacy and safety of oliceridine in patients with postoperative pain. Our endpoints were the proportion of treatment responders to the oliceridine regimen and the incidence of adverse effects such as nausea and vomiting. RESULTS: The analysis showed that more patients responded significantly with oliceridine compared to placebo. The proportion of treatment responders to oliceridine was comparable to that of morphine. Oliceridine had analgesia effects similar to morphine compared to placebo. The incidence of respiratory safety events was significantly lower with oliceridine compared to morphine. Oliceridine was significantly associated with more adverse events such as nausea and vomiting compared to placebo. The safety profile of oliceridine was superior to morphine compared to morphine. CONCLUSIONS: Our systematic review and meta-analysis showed that oliceridine is an effective and safe intravenous analgesic in patients with postoperative pain, producing rapid postoperative analgesic and usually well tolerated, and reducing incidence of adverse events compared to morphine. PROSPERO REGISTRATION: CRD42023391581.
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Analgésicos Opioides , Morfina , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Morfina/efectos adversos , Analgésicos/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Vómitos/inducido químicamente , Náusea/inducido químicamenteRESUMEN
Although traditional opioids such as morphine and oxycodone are commonly used in the management of acute postoperative pain, novel opioids may play a role as alternatives that provide potent pain relief while minimizing adverse effects. In this review, we discuss the mechanisms of action, findings from preclinical studies and clinical trials, and potential advantages of several novel opioids. The more established include oliceridine (biased ligand activity to activate analgesia and downregulate opioid-related adverse events), tapentadol (mu-opioid agonist and norepinephrine reuptake inhibitor), and cebranopadol (mu-opioid agonist with nociceptin opioid peptide activity)-all of which have demonstrated success in the clinical setting when compared to traditional opioids. On the other hand, dinalbuphine sebacate (DNS; semi-synthetic mu partial antagonist and kappa agonist), dual enkephalinase inhibitors (STR-324, PL37, and PL265), and endomorphin-1 analog (CYT-1010) have shown good efficacy in preclinical studies with future plans for clinical trials. Rather than relying solely on mu-opioid receptor agonism to relieve pain and risk opioid-related adverse events (ORAEs), novel opioids make use of alternative mechanisms of action to treat pain while maintaining a safer side-effect profile, such as lower incidence of nausea, vomiting, sedation, and respiratory depression as well as reduced abuse potential.
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Simple one-to three-parameter models routinely used to fit typical dose-response curves and calculate EC50 values using the Hill or Clark equation cannot provide the full picture connecting measured response to receptor occupancy, which can be quite complex due to the interplay between partial agonism and (pathway-dependent) signal amplification. The recently introduced SABRE quantitative receptor model is the first one that explicitly includes a parameter for signal amplification (γ) in addition to those for binding affinity (K d), receptor-activation efficacy (ε), constitutive activity (ε R0), and steepness of response (Hill slope, n). It can provide a unified framework to fit complex cases, where fractional response and occupancy do not match, as well as simple ones, where parameters constrained to specific values can be used (e.g., ε R0 = 0, γ = 1, or n = 1). Here, it is shown for the first time that SABRE can fit not only typical cases where response curves are left-shifted compared to occupancy (κ = K d/EC50 > 1) due to signal amplification (γ > 1), but also less common ones where they are right-shifted (i.e., less concentration-sensitive; κ = K d/EC50 < 1) by modeling them as apparent signal attenuation/loss (γ < 1). Illustrations are provided with µ-opioid receptor (MOPr) data from three different experiments with one left- and one right-shifted response (G protein activation and ß-arrestin2 recruitment, respectively; EC50,Gprt < K d < EC50,ßArr). For such cases of diverging pathways with differently shifted responses, partial agonists can cause very weak responses in the less concentration-sensitive pathway without having to be biased ligands due to the combination of low ligand efficacy and signal attenuation/loss-an illustration with SABRE-fitted oliceridine data is included.
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INTRODUCTION: Opioids remain important in postoperative analgesia although, the focus is on using them as part of multimodal regimens where it is not possible to avoid their use completely. The development of novel agents with more favorable adverse effect profiles may increase safety whilst maintaining efficacy. AREAS COVERED: This article reviews the clinical trials for opioids in late-stage development. The objective of this narrative review is to evaluate the pharmacokinetic properties, safety, tolerability, and analgesic efficacy of these agents in the management of postoperative pain. EXPERT OPINION: Oliceridine appears to be an effective and potentially safer µ opioid receptor agonist. Its main advantages are a relatively fast onset with reduced respiratory depression, nausea, and vomiting. Cebranopadol is an agonist at multiple opioid receptors, of which µ opioid and nociceptin/orphanin FQ peptide (NOP) receptor are most significant. It is an oral drug that appears to have efficacy in neuropathic pain, with reduced respiratory depression and abuse potential. Lastly, morphine-6-glucuronide is an active metabolite of morphine with a slower onset than its parent compound. It has failed to demonstrate appreciable benefit in the context of postoperative analgesia.
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Analgésicos Opioides , Insuficiencia Respiratoria , Humanos , Analgésicos Opioides/efectos adversos , Receptores Opioides , Morfina , Dolor Postoperatorio/tratamiento farmacológico , Insuficiencia Respiratoria/tratamiento farmacológico , Insuficiencia Respiratoria/inducido químicamenteRESUMEN
INTRODUCTION: Oliceridine is a G protein-selective (biased) agonist at the µ-opioid receptor, with less recruitment of ß-arrestin-2, a signaling pathway associated with opioid-related adverse events. Nonclinical evidence showed that oliceridine elicits a rapid systemic analgesic effect while attenuating opioid-related adverse events. AREAS COVERED: Three pivotal studies in patients with moderate-to-severe acute pain, including two randomized, double-blind, placebo- and morphine-controlled efficacy studies following either orthopedic surgery-bunionectomy or plastic surgery-abdominoplasty; and an open-label safety study following a surgical procedure or due to a medical condition. EXPERT OPINION: Poorly controlled acute postoperative pain is associated with poorer recovery, longer hospitalization, increased complications, and worse healthcare outcomes. Recently, oliceridine intravenous injection was approved for use in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. Introduction of this new IV opioid provides a valuable option to manage postoperative pain.
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Dolor Agudo , Compuestos de Espiro , Dolor Agudo/inducido químicamente , Dolor Agudo/tratamiento farmacológico , Adulto , Analgésicos Opioides/uso terapéutico , Humanos , Dolor Postoperatorio/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como Asunto , Compuestos de Espiro/efectos adversos , TiofenosRESUMEN
Oliceridine (Olinvyk® Trevena, PA, USA) was approved by the United States Food and Drug Administration for clinical use on Aug 8, 2020. Even though, the indication of its approval is very restrictive (to manage moderate-to-severe acute pain in adults when the pain is severe enough), for such an innovative opioid, off-label indications are bound to abound. What could be described as the "opioid of the century," it aims to overcome some of the stubbornest barriers to opioid prescribing, namely addiction liability, respiratory depression, and gastrointestinal (GI) side effects, just to name a few. The novel opioid accomplishes this by a unique mechanism of action. By selectively acting on the G-protein sub-pathway in preference to the beta-arrestin, it aims to mitigate these unwanted µ-opioid receptors-associated opioid side effects, while preserving its analgesic activity. What remains to be seen, however, is if these observations seen in phases 2 and 3 trials will be borne in actual large-scale clinical use, both inside and outside the USA. Unfortunately, the field of anesthesia is rife with innovations that have shown enormous promise at the research stage, only to end up as damp squibs when released to the clinicians for general use. Rapcuronium and althesin are some such examples. We aim to present some of the contentious and emerging issues associated with this drug and some of the potential pitfalls of this new opioid.
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BACKGROUND: Oliceridine, a new class of µ-opioid receptor agonist, may be associated with fewer opioid-related adverse events (ORAEs) due to its unique mechanism of action. Thus, it may provide a cost-effective alternative to conventional opioids such as morphine. PATIENTS AND METHODS: Using a decision tree with a 24-hour time horizon, we calculated costs for medication and management of the three most common AEs (oxygen saturation <90%, vomiting, somnolence) following postoperative oliceridine or morphine in high-risk patients. Costs were enumerated as differences in cost of analgesics and resource utilization in the first 24 hours post-surgery. An economic model compared expected AEs and costs in a blended cohort where elderly/obese patients at higher risk for ORAEs received oliceridine while those presumed to be at lower risk received morphine with a cohort that received morphine alone. RESULTS: In high-risk patients, use of oliceridine resulted in overall savings of $363,944 (in 1,000 patients). Implementing a targeted approach of oliceridine utilization in patients with high risk for ORAEs can save a typical hospital system $122,296 in total cost of care. CONCLUSION: Use of oliceridine in postoperative care among patients at high risk provides a favorable health economic benefit compared to the use of morphine.
Oliceridine, a new class of opioid analgesics, administered directly into a vein, is a unique medication in that it provides pain relief equivalent to morphine and may have less costly side effects. It is given in a hospital/clinic or surgery center for the treatment of postoperative pain and can reduce costs compared to other opioid analgesics, possibly due to less side effects. An economic model was developed that compares morphine to oliceridine in patients more likely to experience sides effects due to traditional pain medications, comparing common side effects and pain relief following surgery. Although oliceridine costs more than morphine, in our economic model, the use of oliceridine resulted in cost savings ($363,944 US 2020 Dollars in 1,000 patients), and a positive return of investment of over 7 times, when compared to morphine.
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Analgésicos Opioides , Farmacia , Anciano , Analgésicos Opioides/efectos adversos , Humanos , Morfina/efectos adversos , Dolor Postoperatorio/inducido químicamente , Dolor Postoperatorio/tratamiento farmacológico , Compuestos de Espiro , TiofenosRESUMEN
INTRODUCTION: Opioids acting at the MOP (mu:µ) receptor produce analgesia but also side effects. There is debate suggesting opioid receptors produce analgesia via G-protein and side-effects via ß-arrestin-2 pathways. Opioids targeting G-proteins over the arrestins (bias) offer potential therapeutic advantages. Oliceridine is a putative MOP, G-protein biased agonist. AREAS COVERED: Oliceridine is selective for MOP receptors with greater activity at G-proteins over arrestins. A substantial body of evidence now points to a simpler pharmacological descriptor of partial agonist. Preclinical in vivo data indicates a robust antinociceptive response of shorter duration than morphine. Apollo trials (Phase-III RCT-bunionectomy/abdominoplasty) describe good analgesic efficacy that was non-inferior to morphine with good tolerability and side-effect profile. There is evidence for an improved respiratory safety profile. Oliceridine is approved by the FDA. EXPERT OPINION: Oliceridine will be an important addition to the clinical armamentarium for use for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. Respiratory advantage and the possibility of reduced abuse potential are possible advantages over the use of traditional opioids. Based on a number of excellent, highly detailed studies, oliceridine should be described as a partial agonist; this 'label' does not matter.
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Dolor Postoperatorio , Compuestos de Espiro , Tiofenos , Analgésicos Opioides/efectos adversos , Humanos , Morfina/efectos adversos , Dolor Postoperatorio/tratamiento farmacológico , Compuestos de Espiro/efectos adversos , Tiofenos/efectos adversosRESUMEN
INTRODUCTION: Despite the advances in regional anesthesia and non-opioid systemic analgesia, opioids remain the primary rescue analgesic for moderate to severe pain. However, the risks and side effects of opioid medications are well documented. Oliceridine is a novel opioid receptor agonist which is thought to have less risk of adverse events, such as postoperative nausea and vomiting (PONV) and respiratory depression. AREAS COVERED: In this review, the authors discuss the limitations of the current opioid and non-opioid analgesic options. They also review the pharmacokinetics of oliceridine, its analgesic efficacy, and risk of adverse events; and its added clinical value in managing moderate to severe pain. EXPERT OPINION: Despite the advances in regional anesthesia and multimodal systemic analgesia, opioid free analgesia is only feasible in selected procedures and patients. Oliceridine is effective in the management of moderate to severe pain and appears to be associated with lower risk of nausea and vomiting. The risk of sedation and respiratory depression associated with oliceridine will require further study. The availability of an opioid agonist with a better side effect profile could potentially change the current paradigm of opioid avoidance in postoperative pain management.
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Dolor Agudo , Morfina , Dolor Agudo/tratamiento farmacológico , Adulto , Analgésicos Opioides/efectos adversos , Humanos , Dolor Postoperatorio/tratamiento farmacológico , Náusea y Vómito Posoperatorios , Compuestos de Espiro , TiofenosRESUMEN
The current state of the opioid epidemic has revealed the need of utilizing proper pain management, especially in the postoperative setting where there is overuse of potent analgesics. However, the adequate treatment of pain is necessary to reduce mortality and cost of burden while increasing recovery and improving quality of life. Treatment of pain can be difficult to standardize as the guidelines from the American Pain Society discuss the importance of tailoring treatment options based on a patient's sensitivities and risk factors. An effective fast-acting analgesic with adequate potency and few adverse events is the key to alleviating acute pain. Oliceridine (Olinvyk®, Trevena Inc., Chesterbrook, USA) is a novel G protein-biased µ-opioid receptor agonist designed to decrease opioid-related adverse events (ORAEs) compared to conventional opioids. This article discusses oliceridine's novel mechanism of action and current place in therapy. After a literature search on clinicaltrials.gov, three clinical trials were analyzed to understand the safety and efficacy of oliceridine. These trials demonstrated a comparable efficacy to morphine with a decreased risk for serious adverse events. However, further studies need to be conducted to evaluate the true safety impact of oliceridine compared to conventional opioids.
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Los opioides son los fármacos más utilizados para el tratamiento del dolor agudo. Los opioides convencionales se utilizan ampliamente para el tratamiento del dolor agudo en el entorno postoperatorio. Sin embargo, una de las principales preocupaciones de dichos opioides es su ventana terapéutica, es decir, el intervalo entre las dosis que producen el efecto terapéutico deseado (analgesia) y las dosis que producen efectos adversos relacionados con los opioides (EARO) no deseados. Los opioides convencionales sobre receptores μ tienen una ventana terapéutica estrecha, en parte debido a su mecanismo de acción (MdA): se unen a los receptores μ y activan de forma no selectiva 2 vías de señalización intracelular, lo que provoca analgesia y EARO. Esta revisión explora el potencial clínico de los ligandos de los receptores μ con señalización diferencial. Los agentes con un MdA de "señalización diferencial" representan un enfoque innovador que puede mejorar la ventana terapéutica. Estos agentes modulan la actividad de los receptores μ para activar selectivamente las vías de señalización asociadas a la analgesia, al tiempo que limitan la actividad en las vías de señalización posteriores que conducen a los EARO. Por todo ello, la señalización diferencial puede satisfacer una necesidad no cubierta en el tratamiento del dolor postoperatorio. Oliceridina es un claro exponente de esta nueva generación.(AU)
Opioids are the most drugs used for the management of acute pain. Conventional opioids are widely used for acute pain management in the postoperative setting. However, a primary concern with conventional opioids is their therapeutic window, the range between doses that produce the desired therapeutic effect (analgesia) and doses that produce unwanted opioid-related adverse events (ORAEs). Conventional μ receptor opioids have a narrow therapeutic window in part because of their mechanism of action (MoA): they bind to μ receptors and non-selectively activate two intracellular signaling pathways, leading to analgesia and to ORAEs. This review explores the clinical potential of μ receptor ligands with differential signaling. Agents with a 'differential signaling" MoA represent an innovative approach that may enhance the therapeutic window. These agents modulate μ receptor activity to selectively engage downstream signaling pathways associated with analgesia while limiting activity in downstream signaling pathways that lead to ORAEs. Meanwhile, differential signaling may fulfill an unmet need in the management of postoperative pain. Oliceridine is a clear exponent of this new opioid generation.(AU)
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Humanos , Masculino , Femenino , Manejo del Dolor/tendencias , Analgésicos Opioides/administración & dosificación , Dolor Postoperatorio/tratamiento farmacológico , Dolor Agudo/tratamiento farmacológico , Analgesia , Dolor/tratamiento farmacológico , Manejo del Dolor/métodosRESUMEN
Problems with the treatment of acute pain may arise when a patient is opioid-tolerant, such as those on chronic therapy with opioids or opiate replacement therapy, those who misuse opioids, and those who are in recovery. While some of the adverse effects of opioid medications are well known, it is also important to recognize the roles of tolerance and hyperalgesia. Oliceridine can target and modulate a novel µ-receptor pathway. The G protein-biased agonism of oliceridine allows for effective re-sensitization and desensitization of the mu-opioid receptor, which decreases the formation of opioid tolerance in patients. Oliceridine has been demonstrated to be an effective and relatively safe intravenous analgesic for the treatment of postoperative pain and is generally well tolerated with a favorable side effect profile when compared to morphine. As the prevalence of pain increases, it is becoming increasingly important to find safe and effective analgesics.
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INTRODUCTION: In the management of postoperative acute moderate-to-severe pain, opioids remain an important component. However, conventional opioids have a narrow therapeutic index and are associated with dose-limiting opioid-related adverse events (ORAEs) that can result in worse patient outcomes. Oliceridine, a new intravenous µ-opioid receptor agonist, is shown in nonclinical studies to be biased for G protein signaling (achieving analgesia) with limited recruitment of ß-arrestin (associated with ORAEs). In two phase 3 randomized controlled studies of patients with moderate-to-severe acute pain following hard or soft tissue surgery, in which analgesia was measured using Sum of Pain Intensity Differences (SPID) from baseline over 48 and 24 h (SPID-48 and -24 respectively, oliceridine at demand doses of 0.1, 0.35, or 0.5 mg was highly effective compared to placebo, with a favorable safety profile compared to morphine. This exploratory analysis was conducted to determine whether the safety benefits seen with oliceridine persisted when adjusted for equal levels of analgesia compared to morphine. METHODS: Presence of at least one treatment-emergent ORAE (based on Medical Dictionary for Regulatory Activities [MedDRA]-coded events: hypoxemia, nausea, vomiting, sedation, pruritus, or dizziness) was used as the composite safety endpoint. A logistic regression model was utilized to compare oliceridine (pooled regimens) versus morphine, after controlling for analgesia (using SPID-48 or SPID-24 with pre-rescue scores carried forward 6 h). This analysis excluded patients receiving placebo and was repeated for each study and for pooled data. RESULTS: At a given level of SPID-48 or SPID-24, patients receiving oliceridine were less likely to experience the composite safety endpoint. Although not statistically significant at the 0.05 level in the soft tissue model, the odds ratio (OR) showed a consistent numerical trend for oliceridine, being approximately half that observed with morphine in both the hard (OR 0.499; 95% confidence interval [CI] 0.255, 0.976; p = 0.042) and soft (OR 0.542; 95% CI 0.250, 1.175; p = 0.121) tissue studies. Results from the pooled data were consistent with those observed in the individual studies (OR 0.507; 95% CI 0.304, 0.844; p = 0.009). CONCLUSION: Findings from this exploratory analysis suggest that at comparable levels of analgesia, patients receiving oliceridine were less likely to experience the composite safety endpoint consisting of ORAEs compared to patients treated with morphine. Oliceridine Exhibits Improved Tolerability Compared to Morphine at Equianalgesic Conditions: Exploratory Analysis from Two Phase 3 Randomized Placebo and Active Controlled Trials- A Video (MP4 99188 kb).
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Aim: Oliceridine, a new class of µ-opioid receptor agonist, is selective for G-protein signaling (analgesia) with limited recruitment of ß-arrestin (associated with adverse outcomes) and may provide a cost-effective alternative versus conventional opioid morphine for postoperative pain. Patients & methods: Using a decision tree with a 24-h time horizon, we calculated costs for medication and management of three most common adverse events (AEs; oxygen saturation <90%, vomiting and somnolence) following postoperative oliceridine or morphine use. Results: Using oliceridine, the cost for managing AEs was US$528,424 versus $852,429 for morphine, with a net cost savings of $324,005. Conclusion: Oliceridine has a favorable overall impact on the total cost of postoperative care compared with the use of the conventional opioid morphine.
Lay abstract Oliceridine, a new class of opioid pain medication, given in a vein, is a unique medication in that it provides pain relief comparable to morphine and may have less costly side effects. It is given in a hospital or surgery center for the treatment of postoperative pain and can save money compared with other opioid pain medicines due to fewer side effects. An economic model was developed to compare morphine to oliceridine for common side effects and pain relief following surgery. Oliceridine use resulted in a cost saving (US$324,005; 2020 US dollars) when compared with morphine.
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Dolor Agudo , Compuestos de Espiro , Dolor Agudo/tratamiento farmacológico , Análisis Costo-Beneficio , Humanos , TiofenosRESUMEN
Successful pharmacological innovations that have made a difference in daily practice are rare in the world of anesthesia and sedation. After many years of research, it seems that we finally have two new drug innovations that are likely to change the paradigm of moderate and deep sedation. These are oliceridine and remimazolam. Both have been in development for over a decade. Oliceridine was synthesized in a lab as an entirely new molecule. It is a biased µ- receptor agonist that acts preferentially on the G-protein pathway (which is responsible for analgesia). At least in lower doses, it has minimal effect on the beta-arrestin pathway, which is responsible for unwanted effects of µ-opioid receptor activation such as respiratory depression and gastrointestinal dysfunction. Like any other µ- receptor agonist, it produces appropriate dose-dependent analgesia. Remimazolam is structurally similar to midazolam; however, it has an additional ester linkage that delivers the kinetics of remifentanil. As a result, while pharmacodynamically identical to midazolam, remimazolam is metabolized by ester hydrolysis and subsequently its elimination is rapid and predictable. The present review discusses the two drugs in detail with a particular emphasis on their potential role in moderate and deep sedation.