Nalmefene 18mg tablets

Background: Bronchoscopy examination is a common clinical diagnostic method. However, due to its unique operational characteristics, the procedure often induces discomfort and pain in patients. The combined use of sufentanil and nalmefene offers advantages in effectively reversing opioid-induced respiratory depression without compromising analgesic effects. However, a comprehensive analysis report on the combined use of different doses of sufentanil and nalmefene in bronchoscopy examinations has not been reported. The aim of this subject is to investigate the application effects of different doses of sufentanil combined with nalmefene in bronchoscopy. Methods: Using computer-based and manual methods to retrieve relevant keywords, we searched the databases of PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang from inception to the present to find studies evaluating the application effects of different doses of sufentanil combined with nalmefene in bronchoscopy examinations. The quality of the included studies was assessed, and meta-analysis was conducted using RevMan 5.3 software. Results: ), and Riker sedation-agitation scale (SAS score) was significantly reduced (P<0.05). However, there were no significant differences in other adverse events (P>0.05). Subgroup analysis showed fewer adverse reactions at 0.4 µg/kg sufentanil concentration compared to 0.2 and 0.8 µg/kg, with only hypertension differing significantly. Conclusions: In clinical practice, considering the use of sufentanil combined with nalmefene can improve patients' experience during bronchoscopy examinations. However, it should be noted that this approach may not be suitable for all patients, and clinicians need to choose appropriate analgesic and sedative methods for bronchoscopy examinations based on patients' conditions and individual differences. Furthermore, it is important to recognize that this study has some limitations and further research is needed to evaluate the efficacy and safety of this approach in other types of endoscopic examinations, as well as to compare the effects and safety of different drug combinations.

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Purpose: This study was designed to investigate the effects of preadministration of nalmefene before general anesthesia induction on sufentanil-induced cough (SIC) in patients undergoing breast surgery. Patients and Methods: A total of 105 patients scheduled for elective breast surgery under general anesthesia were selected and randomly assigned into three groups: normal saline (Group C), low-dose nalmefene 0.1 μg·kg − 1 (Group LN), and high-dose nalmefene 0.25 μg·kg − 1 (Group HN). Sufentanil 0.5 μg·kg − 1 was injected intravenously within 2 s after 5 min of intervention. The count and severity of cough within 2 min after sufentanil injection, as well as the time to first cough, were recorded. In addition, we also collected intraoperative hemodynamic data, postoperative pain scores, the incidence of receiving rescue analgesics, and side effects up to 24 h after surgery. Results: Compared to Group C, the incidence of SIC was significantly lower in Group LN and HN (64.7% vs 30.3% and 14.7%, respectively; P < 0.001), but no significant difference was observed between the two groups ( P =0.126). Compared to Group C, the risk factors decreased by 53.4% (95% confidence interval [CI] =0.181– 0.735, P =0.008) in Group LN and by 75.9% (95% CI=0.432– 0.898, P =0.001) in Group HN. Of the patients with SIC, less frequent SIC within 2 min after induction and a lower proportion of severe coughs were observed than Group C ( P < 0.05), and no difference was detected between Group LN and HN. Additionally, the onset time to the first SIC did not differ significantly between the groups. Intraoperative hemodynamic data, postoperative pain scores, and side effects in the first 24 h did not differ among the groups. Conclusion: Preadministration of nalmefene prior to induction of general anesthesia effectively suppressed SIC in patients undergoing breast surgery, without affecting intraoperative hemodynamic fluctuation and postoperative pain intensity. Keywords: nalmefene, general anesthesia, sufentanil, cough, breast surgery

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OBJECTIVES: This randomised controlled trial aims to evaluate the impact of low-dose intravenous nalmefene on anaesthesia recovery in adult patients aged 18-65 undergoing surgery under general anaesthesia. DESIGN: This was a multicentre, randomised, double-blind trial with two parallel arms clinical study. SETTING: Four hospitals from China PARTICIPANTS: A total of 514 patients aged 18-65 who underwent elective orthopaedic, urologic and thoracic surgeries. INTERVENTIONS: On completion of skin suturing, the intervention group received a single intravenous dose of nalmefene (0.25 µg/kg). The control group received an equivalent volume of normal saline at the same time point. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the interval time between the end of anaesthesia and the Aldrete score ≥9 being achieved in the postanaesthesia care unit (PACU). The secondary endpoints included the time interval from the end of operation to extubation; Richmond Agitation Sedation Scale (RASS) score at extubation; the time at Montreal Cognitive Assessment Scale (MoCA) orientation score ≥5; visual analogue scale (VAS) score in PACU and 24 hours postoperatively. RESULTS: 514 patients were included in the Intention-to-Treat (ITT) analysis. The time interval between the end of anaesthesia and Aldrete score reached ≥9 in PACU was significantly shorter in the intervention group than in the control group (mean (SD) 24.8 (11.8) min vs 33.8 (12.5) min; 95% CI -8.8 (-10.8 to -6.7); p<0.001). Furthermore, the time interval from the end of surgery to extubation was shorter in the intervention than in the control group (mean (SD) 20.0 (9.9)min vs 27.6 (11.6) min; 95% CI -7.6 (-9.43 to -5.7), p<0.001). The time at Montreal cognitive assessment score ≥5 was also shorter in the control than in the intervention group (mean (SD) 20.0 (15.9) min vs 27.0 (20.5) min; 95% CI -7.0 (-10.2 to -3.8); p<0.001). Compared with the control group, the intervention group had better analgesic effect at the recovery endpoint (P Aldrete score ≥A was achieved as well as lower 24 hours points postoperatively (p<0.05)). CONCLUSIONS: In patients aged 18-65 who underwent elective orthopaedic, urologic and thoracic surgeries, low-dose nalmefene administered at the end of surgery can accelerate postanaesthesia recovery without compromising analgesic effects. TRIAL REGISTRATION NUMBER: NCT04713358.

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Nalmefene hydrochloride was first discovered as an opioid antagonist derivative of naltrexone in 1975. It is among the most potent opioid antagonists currently on the market and is differentiated from naloxone and naltrexone by its partial agonist activity at the kappa-opioid receptor which may benefit in the treatment of alcohol use disorder. Oral nalmefene has been approved in the European Union for treatment of alcohol use disorder since 2013. As of 2023, nalmefene is available in the United States as an intranasal spray for reversal of opioid overdose but is not approved for alcohol or opioid use disorder as a maintenance treatment. The substantially longer half-life of nalmefene and 5-fold higher binding affinity to opioid receptors makes it a superior agent over naloxone in the reversal of high potency synthetic opioids like fentanyl and the emerging nitazenes. Nalmefene presents with a comparable side effect profile to other opioid antagonists and should be considered for further development as a maintenance treatment for opioid and other substance use disorders.

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Nalmefene is a high-affinity, long-duration opioid antagonist that was approved in 1995 as an injection for the treatment of opiate overdose, but subsequently withdrawn (2008) for reasons other than safety or effectiveness. The dramatic rise in opioid overdose deaths over the past 7-8 years catalyzed the development of an intranasal (IN) formulation of nalmefene for the emergency treatment of opioid overdose. The studies described here compare the pharmacokinetic properties and safety profiles of an IN formulation containing nalmefene (2.7 mg in 0.1 mL) to an approved 1 mg intramuscular (IM) dose. IN nalmefene produced maximum plasma concentrations that were significantly higher than observed following the IM dose (12.2 and 1.77 ng/mL, respectively). The time to reach maximum plasma concentrations was also faster following IN administration (0.25 and 0.33 hours, respectively) with significant differences in plasma concentrations manifested as early as 2.5 minutes after administration (NCT04759768). The plasma half-life of nalmefene was similar following IM and IN administration (10.6-11.4 hours). Furthermore, dose-normalized nalmefene exposure was similar for both 1 spray in each nostril and 2 sprays in the same nostril compared to a single spray in each nostril (NCT05219669). There were no sex differences in the pharmacokinetic properties of either IN or IM nalmefene. In an era when almost 90% of opioid overdose deaths have been linked to high-potency synthetic opioids, the ability to rapidly deliver high concentrations of nalmefene could represent an important tool for reducing both morbidity and mortality.

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The fatal overdose crisis claims nearly 200 lives daily in the United States (U.S). Evolutions in the illicit drug supply, such as the addition of sedative adulterants and a shift to synthetic opioids such as fentanyl, have driven increasing rates of both fatal and non-fatal overdose. Specifically, synthetic opioid usage of fentanyl was implicated in 68 % of the U.S. drug overdose deaths in 2022 alone. This has placed tremendous burden on communities, emergency medical services, and healthcare systems, and contributed to tragedy and grief both in the U.S. and worldwide. Despite the availability of effective opioid antagonist medications and standards of care, there has been increased interest in research and development of alternative opioid overdose reversal agents by the National Institutes of Health (NIH) in partnership with pharmaceutical manufacturers over the last decade. The U.S. Food and Drug Administration (FDA) recently approved nalmefene (Opvee) a mu-opioid receptor antagonist that boasts an extended half-life and stronger mu-receptor affinity compared to the standard of care use of naloxone for opioid reversal. In this article, we explore the medical need and ramifications of the introduction of longer-acting opioid antagonists in the current opioid overdose landscape. Existing data highlight the effectiveness of already available naloxone products as a safe and effective standard of care. These data support the notion that stronger, longer-acting agents may be unnecessary, and their existence may cause undue harm, such as more severe and/or prolonged withdrawal symptoms, lead to challenging patient interactions, and complicate the initiation of medications for opioid use disorder. More evidence is needed before healthcare professionals should implement the use of stronger, longer-acting opioid antagonists for reversing opioid overdose over evidence-based, cost-effective naloxone.

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An open-label, randomized, crossover study in healthy volunteers compared the reversal of remifentanil-induced respiratory depression by intranasal (IN) naloxone hydrochloride (4 mg) to IN nalmefene (2.7 mg) (NCT04828005). Subjects were administered a hypercapnic gas mixture which produces an elevation in minute ventilation (MV), a result of the ventilatory response to hypercapnia. Subjects breathed a hypercapnic gas mixture through a tight-fitting mask for an initial period of 46 min prior to a series of mask "holidays" introduced to reduce subject discomfort and encourage study completion. Ten minutes after initiating the hypercapnic gas mixture, a remifentanil bolus was administered, and an infusion continued for the study duration. Subjects were administered either naloxone or nalmefene 15 min after initiating the remifentanil infusion and MV monitored for 21 min followed by a mask holiday. Both nalmefene and naloxone produced a time-dependent reversal of remifentanil-induced reductions in MV measured 2.5-20 min post administration. At the primary endpoint (5 min post administration), nalmefene increases in MV (5.75 L/min) were nearly twice that produced by naloxone (3.01 L/min) (P < .0009); the point estimate favors nalmefene, demonstrating non-inferiority and superiority. In this model of opioid-induced respiratory depression, nalmefene has a more rapid onset of action than naloxone, which required 20 min to achieve a comparable reversal of respiratory depression. Both nalmefene and naloxone were well tolerated by healthy volunteers. This rapid onset of action may prove particularly valuable in an era when over 90% of fatalities are linked to synthetic opioid overdose.

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Introduction: Using a validated translational model that quantitatively predicts opioid-induced respiratory depression and cardiac arrest, we compared cardiac arrest events caused by synthetic opioids (fentanyl, carfentanil) following rescue by intranasal (IN) administration of the μ-opioid receptor antagonists naloxone and nalmefene. Methods: This translational model was originally developed by Mann et al. (Clin Pharmacol Ther 2022) to evaluate the effectiveness of intramuscular (IM) naloxone. We initially implemented this model using published codes, reproducing the effects reported by Mann et al. on the incidence of cardiac arrest events following intravenous doses of fentanyl and carfentanil as well as the reduction in cardiac arrest events following a standard 2 mg IM dose of naloxone. We then expanded the model in terms of pharmacokinetic and µ-opioid receptor binding parameters to simulate effects of 4 mg naloxone hydrochloride IN and 3 mg nalmefene hydrochloride IN, both FDA-approved for the treatment of opioid overdose. Model simulations were conducted to quantify the percentage of cardiac arrest in 2000 virtual patients in both the presence and absence of IN antagonist treatment. Results: Following simulated overdoses with both fentanyl and carfentanil in chronic opioid users, IN nalmefene produced a substantially greater reduction in the incidence of cardiac arrest compared to IN naloxone. For example, following a dose of fentanyl (1.63 mg) producing cardiac arrest in 52.1% (95% confidence interval, 47.3-56.8) of simulated patients, IN nalmefene reduced this rate to 2.2% (1.0-3.8) compared to 19.2% (15.5-23.3) for IN naloxone. Nalmefene also produced large and clinically meaningful reductions in the incidence of cardiac arrests in opioid naïve subjects. Across dosing scenarios, simultaneous administration of four doses of IN naloxone were needed to reduce the percentage of cardiac arrest events to levels that approached those produced by a single dose of IN nalmefene. Conclusion: Simulations using this validated translational model of opioid overdose demonstrate that a single dose of IN nalmefene produces clinically meaningful reductions in the incidence of cardiac arrest compared to IN naloxone following a synthetic opioid overdose. These findings are especially impactful in an era when >90% of all opioid overdose deaths are linked to synthetic opioids such as fentanyl.

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