Formulation Of Naloxone Research Articles

Intranasal naloxone rapidly occupies brain mu-opioid receptors in human subjects.

Nasal spray formulations of naloxone, a mu-opioid receptor (MOR) antagonist, are currently used for the treatment of opioid overdose. They may have additional therapeutic utility also in the absence of opioid agonist drugs, but the onset and duration of action at brain MORs have been inadequately characterized to allow such projections. This study provides initial characterization of brain MOR availability at high temporal resolution following intranasal (IN) naloxone administration to healthy volunteers in the absence of a competing opioid agonist. Fourteen participants were scanned twice using positron emission tomography (PET) and [11C]carfentanil, a selective MOR agonist radioligand. Concentrations of naloxone in plasma and MOR availability (relative to placebo) were monitored from 0 to 60 min and at 300-360 min post naloxone. Naloxone plasma concentrations peaked at ~20 min post naloxone, associated with slightly delayed development of brain MOR occupancy (half of peak occupancy reached at ~10 min). Estimated peak occupancies were 67 and 85% following 2 and 4 mg IN doses, respectively. The estimated half-life of occupancy disappearance was ~100 min. The rapid onset of brain MOR occupancy by IN naloxone, evidenced by the rapid onset of its action in opioid overdose victims, was directly documented in humans for the first time. The employed high temporal-resolution PET method establishes a model that can be used to predict brain MOR occupancy from plasma naloxone concentrations. IN naloxone may have therapeutic utility in various addictions where brain opioid receptors are implicated, such as gambling disorder and alcohol use disorder.

3570 The Regulatory Landscape of Products to Treat Opioid Overdose

OBJECTIVES/SPECIFIC AIMS: Since 1971, Naloxone has been the only FDA approved opioid antagonist indicated for use after opioid overdose. New formulations of Naloxone have been introduced into the market, including an injectable, auto-injector, and nasal spray. However, Naloxone is short-acting and as such often requires multiple doses and may induce severe withdrawal symptoms. This study examines the regulatory framework to understand the evolution of products indicated to treat opioid overdose and the landscape of therapies in development. Furthermore, this study examines how the Food and Drug Administration (FDA) and other government agencies have approached the opioid crisis. METHODS/STUDY POPULATION: A PubMed search of “naloxone AND opioid overdose” with the filter “humans” was conducted to understand Naloxone’s regulatory framework. The term “naloxone” was searched on the Drugs@FDA: Approved Drug Products database. Additionally, “nalmefene” was searched on ClinicalTrials.gov. To examine the opioid antagonist market landscape, a PubMed search of “opioid antagonist AND opioid overdose” with the filters “humans” and “clinical trial,” and a ClinicalTrials.gov search of “opioid antagonist and opioid overdose,” were conducted. Government agency reports were reviewed and cataloged. RESULTS/ANTICIPATED RESULTS: Preliminary findings suggest a lack of innovation in the development of novel opioid antagonists. Most literature review findings focused on already-marketed Naloxone products, including the original injectable approved in 1971, the 2014 Evzio Auto-Injector, and the 2015 Narcan Nasal Spray (Figure 1). For example, there were 14 results yielded from the FDA approvals database, but none of these results represented a new opioid antagonist molecule. A longer-acting opioid antagonist, Nalmefene injectable, was approved in 1995 but has since been removed from the market due to low sales. Our initial ClinicalTrials.gov search using condition “opioid overdose” and other terms “opioid antagonist”,revealed no new studies being conducted on alternative opioid antagonist treatments for opioid overdose. Findings only focused on the distribution, co-dispensing, intervention, pharmacokinetics/pharmacodynamics (PK/PD) of Naloxone (Figure 2). However, a Google search yielded one new trial with an opioid antagonist by Opiant Pharmaceuticals, almost fifty years after FDA’s approval of Naloxone. A ClinicalTrials.gov search was then performed using the search term “nalmefene” to find whether Opiant Pharmaceuticals’ trial was in the ClinicalTrials.gov database. However, the Opiant trial is phase I, and as such does not require reporting on ClinicalTrials.gov. In 2017, the National Institutes of Health (NIH) launched an initiative for longer-acting opioid antagonist formulations. In 2018, Opiant Pharmaceuticals announced positive phase I results for intranasal Nalmefene. The potential return of Nalmefene in intranasal form may play a significant role in reducing overdoses, especially in cases where a longer-acting opioid antagonist is necessary. Opiant Pharmaceuticals’ trial commenced after the NIH announced their initiative; furthermore, the NIH’s National Institute on Drug Abuse granted the company $7.4 million to further the investigation of this drug. We will continue to research drugs that have previously been studied for the indication of treating opioid overdose in the United States and abroad and catalog them. DISCUSSION/SIGNIFICANCE OF IMPACT: The abuse and misuse of opioids in the United States has caused an epidemic accounting for over 115 opioid-overdose deaths each day, devastating our nation, both socially and economically. The United States spends $78.5 billion annually to combat the misuse of these drugs. Due to the severity of the opioid crisis, efforts to better understand approved therapies and investigational products in development to treat opioid overdose will be of significance moving forward. This research can inform agencies who are developing strategies to reduce opioid overdoses and pharmaceutical product developers about the current opioid antagonist landscape.

Increases in controlled-release oxycodone utilisation following the subsidy of oxycodone with naloxone formulations: An Australian population-based study.

Despite increasing use of oxycodone/naloxone controlled-release (CR) in Australia, little is known about how it has affected the overall oxycodone CR market since its subsidy in 2011. We used Pharmaceutical Benefits Scheme dispensing claims (2006-2016) and interrupted time series analysis to examine changes in the quarterly rates of dispensing of oral oxycodone CR formulations (oxycodone/naloxone CR and single-ingredient oxycodone CR) and new oxycodone CR treatment episodes. We also performed a retrospective cohort study in a sample of people initiating a new oxycodone CR treatment episode in 2009, 2012/2013, and 2016 to compare opioid utilisation patterns over time. The subsidy of oxycodone/naloxone CR was associated with a 1.6-fold increase in the growth rate of oxycodone CR dispensing, resulting from rapid uptake of low strength (≤5mg) oxycodone/naloxone CR. In our cohort of initiators, the number of new oxycodone CR treatment episodes increased 2.1-fold between 2009 and 2016; in 2016, 91.4% of new treatment episodes involved oxycodone/naloxone CR. Comparing 2016 with 2009, we observed an increase in people initiating with a tablet strength less than or equal to 5-mg (risk difference [RD]=21.1%, 95% CI, 19.9%-22.4%) in people initiating with no other opioid dispensing 90days prior to initiation (RD=5.2%, 3.8%-6.6%) and with no further opioid dispensing 90days after initiation (RD=8.8%, 7.4%-10.2%). After its subsidy, the uptake of low-dose oxycodone/naloxone CR was greater than expected if it were substituting the single-ingredient oxycodone CR, resulting in an expansion of the oxycodone CR market.

No more prior authorization in Pennsylvania for MAT

Several state agencies in Pennsylvania have helped to negotiate an agreement under which seven major insurers in the state will remove prior‐authorization barriers to the full array of medication‐assisted treatment (MAT) options for opioid dependence. Under the agreement announced this month, each insurer will expand plan members' access to methadone, at least one buprenorphine‐naloxone combination product and both the oral and injectable formulations of naltrexone, as well as at least one nasal formulation of naloxone for opioid overdose reversal.

The changing landscape of naloxone availability in the United States, 2011 – 2017

Opioid overdose deaths have been on the rise in the United States since 1999. Naloxone is a competitive opioid antagonist that rapidly reverses opioid overdose. The implementation of naloxone access laws and development of naloxone formulations that can be administered by laypersons have coincided with changes in the landscape of naloxone availability in the United States. Using data from IQVIA’s National Prescription Audit® we present the number of naloxone prescriptions dispensed quarterly from 2011 through the second quarter of 2017. The data demonstrate that nationwide naloxone dispensing increased nearly eight-fold from the fourth quarter of 2015 to the second quarter of 2017. Narcan® was the most commonly prescribed naloxone formulation as of the second quarter of 2017, accounting for 68% of prescriptions during that quarter followed by Evzio® (20%). There was considerable variability in the extent to which states experienced increases in naloxone dispensing, which may represent a general state-specific response to the opioid crisis, rather than direct association with opioid overdose death rates in a particular state. Although naloxone access laws continue to increase the amount of naloxone dispensed, cost remains a concern in terms of wide distribution of the life-saving medication.

Development and implementation of procedures for outpatient naloxone prescribing at a large academic medical center.

An interprofessional initiative to operationalize outpatient naloxone prescribing at a large academic medical center is described. The initiative was carried out by a work group of clinical pharmacists and pharmacy administrators in collaboration with physicians and nursing staff leaders from multiple practice settings. An opioid overdose risk-assessment guide was developed on the basis of literature review and expert opinion. An institutional policy to guide identification of high-risk patient populations and facilitate naloxone prescribing and dispensing was developed and vetted by multiple expert committees. Patient education materials were created, and patients at high risk for opioid overdose were educated about overdose risk factors and naloxone use by a pharmacist and/or nurse before discharge or, in some cases, by outpatient pharmacists; when feasible, patients' friends, family members, and/or caregivers were included in education sessions. Interventions included distribution of a pamphlet emphasizing the importance of contacting emergency medical services personnel immediately in the event of an overdose, depicting the process for administration of injectable and nasal spray formulations of naloxone, and providing information on other first-response steps. Collaboration with outpatient pharmacies allowed for successful dispensing of naloxone prescriptions. The implementation of an outpatient naloxone prescribing policy at a large academic medical center created a streamlined approach for the interprofessional healthcare team to use in providing naloxone education and improved naloxone access to patients at high risk for opioid overdose.

Factors associated with how often community pharmacists offer and dispense naloxone.

A recent Surgeon General's report encourages people to ask pharmacists about naloxone, but whether pharmacists are well-prepared to respond to these requests is unclear. Determine factors that are associated with how often pharmacists offer and dispense naloxone. A convenience sample of 457 community pharmacists in North Carolina completed a 5-min online survey. Linear regressions were conducted to identify factors that are associated with how often pharmacists offer and dispense naloxone. Pharmacists' self-reported barriers to teaching naloxone administration were identified. Most pharmacists (81.2%) worked in pharmacies that stocked naloxone, but many never offered (36.6%) or dispensed (19.4%) naloxone. Pharmacists offered (β = 0.15, p < 0.01) and dispensed (β = 0.15, p < 0.01) naloxone more often when their pharmacy stocked more naloxone formulations. Pharmacists who were more comfortable discussing naloxone offered it more often (β = 0.26, p = 0.001). Pharmacists who worked in regional/local/grocery chain pharmacies dispensed and offered naloxone less often than other pharmacy types. Barriers to teaching naloxone administration included: time constraints, inadequate training, and perceived lack of patient comprehension. Many community pharmacists do not offer or dispense naloxone. Pharmacists who are uncomfortable discussing naloxone or work at smaller chain pharmacies may benefit from targeted naloxone training.

Drugmakers Vow to Donate Take-Home Naloxone While Prices for Drug Soar

Drugmakers Vow to Donate Take-Home Naloxone While Prices for Drug Soar

Trends and economic drivers for United States naloxone pricing, January 2006 to February 2017

Anecdotal evidence indicates that naloxone prices have risen in recent years, but limited research has examined the magnitude of these increases and potential causes. We contribute nationally representative evidence to help answer each of these questions, including wholesale pricing data from a proprietary drug sales database spanning January 2006 to February 2017. We find that all formulations of naloxone increased in price since 2006 except for Narcan Nasal Spray. These cumulative increases totaled 2281% for the 0.4 MG single-dose products, 244% for the 2 MG single-dose products, 3797% for the 4 MG multi-dose products, and 469% for the 0.4 MG Evzio auto-injector. We believe that increased demand for naloxone from the opioid epidemic may explain the more gradual price increases for the 0.4 MG single-dose and 4 MG multi-dose products prior to 2012. On the other hand, we believe that the sudden, sustained prices increases occurring for all of the products since 2012 may be the result of a drug shortage for the 0.4 MG single-dose products and the fact that each naloxone product has historically been sold by only a single competitor.

Pharmacokinetic properties of intranasal and injectable formulations of naloxone for community use: a systematic review.

To assess the pharmacokinetic properties of community-use formulations of naloxone for emergency treatment of opioid overdose. Systematic literature review based on searches of established databases and congress archives. Seven studies met inclusion criteria: two of US FDA-approved intramuscular (im.)/subcutaneous (sc.) auto-injectors, one of an FDA-approved intranasal spray, two of unapproved intranasal kits (syringe with atomizer attachment) and two of intranasal products in development. The pharmacokinetics of im./sc. auto-injector 2mg and approved intranasal spray (2 and 4mg) demonstrated rapid uptake and naloxone exposure exceeding that of the historic benchmark (0.4 mg im.), indicating that naloxone exposure was adequate for reversal of opioid overdose.

Prescribing naloxone for opioid overdose intervention.

To provide an update on prescription of naloxone as a harm-reduction strategy, PubMed was searched to identify publications relevant to naloxone prescribing for reversal of opioid overdose. Opportunities now exist to expand naloxone use, although evidence suggests these are often missed or underexploited. The US FDA has approved an intranasal naloxone spray and an autoinjector naloxone formulation for community use. Effective use of naloxone in community settings requires screening to identify patients at risk of opioid overdose, discussing naloxone use with patients and their relatives, and providing appropriate training. The tools exist to expand the use of naloxone more widely into the community, thereby creating an opportunity to reduce opioid overdose fatalities.

America's Opioid Epidemic: a Comprehensive Review and Look into the Rising Crisis.

In the USA, there has been a sharp increase in heroin, prescription opiate, and illicitly manufactured fentanyl abuse with overdoses tripling since the 1990s. Several states have been deemed as "high-burden" abuse states where there is a greater proportion of synthetic opiate use. During the same period that prescription limitations were initially implemented throughout the country, the fentanyl epidemic started nationwide. In the setting of data demonstrating an almost fourfold increase in overdose deaths from 1999 to 2008, states began restricting access to Food and Drug Agency (FDA) approved opioid medications. Another factor further exacerbating the opioid crises is that the cost of all formulations of naloxone has increased significantly over the past several years. In order to combat the opioid epidemic, stricter prescribing practices and prescription-monitoring programs have been instituted. Also, improvements in abuse-deterrent strategies for all opioid preparations can play an important role by increasing the safety of these medications and is a major focus of the FDA.

Naloxone formulation for overdose reversal preference among patients receiving opioids for pain management

BackgroundOpioid-related overdose has increased 137% in the past decade. Training nonmedical bystanders to administer naloxone (Narcan™) is a widely-researched intervention that has been associated with decreases in overdose rates in the communities in which it has been implemented. A recent review advocated for noninjectable formulations of naloxone, however patient preference for naloxone formulations has not yet been examined (Strang et al., 2016). MethodsTwo cohorts of respondents (N1 = 501, N2 = 172) who reported currently being prescribed an opioid for pain management were recruited through the crowd-sourcing program Amazon Mechanical Turk (MTurk) to assess their preference for naloxone formulations. All respondents were provided a description of different formulations and asked to indicate all formulations they would be willing to administer for overdose reversal and to then rank formulations in order of preference. ResultsResults were remarkably similar across both cohorts. Specifically, respondents preferred noninjectable formulations (intranasal, sublingual, buccal) over injectable (intravenous, intramuscular) formulations. A small percent (8.9%–9.8%) said they would never be willing to administer naloxone. An identical percent of respondents in both cohorts (44.9%) rated intranasal as their most preferred formulation. ConclusionsTwo independent cohorts of respondents who were receiving opioid medications for pain management reported a preference for noninjectable over injectable formulations of naloxone to reverse an opioid overdose. Though initial preference is only one of many factors that impacts ultimate public acceptance and uptake of a new product, these results support the additional research and development of noninjectable naloxone formulations.

Pharmacokinetics and -dynamics of intramuscular and intranasal naloxone: an explorative study in healthy volunteers

This study aimed to develop a model for pharmacodynamic and pharmacokinetic studies of naloxone antagonism under steady-state opioid agonism and to compare a high-concentration/low-volume intranasal naloxone formulation 8mg/ml to intramuscular 0.8mg. Two-way crossover in 12 healthy volunteers receiving naloxone while receiving remifentanil by a target-controlled infusion for 102min. The group were subdivided into three different doses of remifentanil. Blood samples for serum naloxone concentrations, pupillometry and heat pain threshold were measured. The relative bioavailability of intranasal to intramuscular naloxone was 0.75. Pupillometry showed difference in antagonism; the effect was significant in the data set as a whole (p < 0.001) and in all three subgroups (p < 0.02-p < 0.001). Heat pain threshold showed no statistical difference. A target-controlled infusion of remifentanil provides good conditions for studying the pharmacodynamics of naloxone, and pupillometry was a better modality than heat pain threshold. Intranasal naloxone 0.8mg is inferior for a similar dose intramuscular. Our design may help to bridge the gap between studies in healthy volunteers and the patient population in need of naloxone for opioid overdose. clinicaltrials.gov : NCT02307721.

Cost-Effectiveness of Take-Home Naloxone for the Prevention of Overdose Fatalities among Heroin Users in the United Kingdom

Background: Heroin overdose is a major cause of premature death. Naloxone is an opioid antagonist that is effective for the reversal of heroin overdose in emergency situations and can be used by nonmedical responders. Objective: Our aim was to assess the cost-effectiveness of distributing naloxone to adults at risk of heroin overdose for use by nonmedical responders compared with no naloxone distribution in a European healthcare setting (United Kingdom). Methods: A Markov model with an integrated decision tree was developed based on an existing model, using UK data where available. We evaluated an intramuscular naloxone distribution reaching 30% of heroin users. Costs and effects were evaluated over a lifetime and discounted at 3.5%. The results were assessed using deterministic and probabilistic sensitivity analyses. Results: The model estimated that distribution of intramuscular naloxone, would decrease overdose deaths by around 6.6%. In a population of 200,000 heroin users this equates to the prevention of 2,500 premature deaths at an incremental cost per quality-adjusted life year (QALY) gained of £899. The sensitivity analyses confirmed the robustness of the results. Conclusions: Our evaluation suggests that the distribution of take-home naloxone decreased overdose deaths by around 6.6% and was cost-effective with an incremental cost per QALY gained well below a £20,000 willingness-to-pay threshold set by UK decision-makers. The model code has been made available to aid future research. Further study is warranted on the impact of different formulations of naloxone on cost-effectiveness and the impact take-home naloxone has on the wider society.

Intranasal naloxone and related strategies for opioid overdose intervention by nonmedical personnel: a review.

Deaths due to prescription and illicit opioid overdose have been rising at an alarming rate, particularly in the USA. Although naloxone injection is a safe and effective treatment for opioid overdose, it is frequently unavailable in a timely manner due to legal and practical restrictions on its use by laypeople. As a result, an effort spanning decades has resulted in the development of strategies to make naloxone available for layperson or “take-home” use. This has included the development of naloxone formulations that are easier to administer for nonmedical users, such as intranasal and autoinjector intramuscular delivery systems, efforts to distribute naloxone to potentially high-impact categories of nonmedical users, as well as efforts to reduce regulatory barriers to more widespread distribution and use. Here we review the historical and current literature on the efficacy and safety of naloxone for use by nonmedical persons, provide an evidence-based discussion of the controversies regarding the safety and efficacy of different formulations of take-home naloxone, and assess the status of current efforts to increase its public distribution. Take-home naloxone is safe and effective for the treatment of opioid overdose when administered by laypeople in a community setting, shortening the time to reversal of opioid toxicity and reducing opioid-related deaths. Complementary strategies have together shown promise for increased dissemination of take-home naloxone, including 1) provision of education and training; 2) distribution to critical populations such as persons with opioid addiction, family members, and first responders; 3) reduction of prescribing barriers to access; and 4) reduction of legal recrimination fears as barriers to use. Although there has been considerable progress in decreasing the regulatory and legal barriers to effective implementation of community naloxone programs, significant barriers still exist, and much work remains to be done to integrate these programs into efforts to provide effective treatment of opioid use disorders.

Naloxone for heroin, prescription opioid, and illicitly made fentanyl overdoses: Challenges and innovations responding to a dynamic epidemic

Community-based overdose prevention programs first emerged in the 1990’s and are now the leading public health intervention for overdose. Key elements of these programs are overdose education and naloxone distribution to people who use opioids and their social networks. We review the evolution of naloxone programming through the heroin overdose era of the 1990’s, the prescription opioid era of the 2000’s, and the current overdose crisis stemming from the synthetic opioid era of illicitly manufactured fentanyl and its analogues in the 2010’s. We present current challenges arising in this new era of synthetic opioids, including variable potency of illicit drugs due to erratic adulteration of the drug supply with synthetic opioids, potentially changing efficacy of standard naloxone formulations for overdose rescue, potentially shorter overdose response time, and reports of fentanyl exposure among people who use drugs but are opioid naïve. Future directions for adapting naloxone programming to the dynamic opioid epidemic are proposed, including scale-up to new venues and social networks, new standards for post-overdose care, expansion of supervised drug consumption services, and integration of novel technologies to detect overdose and deliver naloxone.

International patent applications for non-injectable naloxone for opioid overdose reversal: Exploratory search and retrieve analysis of the PatentScope database.

Non-injectable naloxone formulations are being developed for opioid overdose reversal, but only limited data have been published in the peer-reviewed domain. Through examination of a hitherto-unsearched database, we expand public knowledge of non-injectable formulations, tracing their development and novelty, with the aim to describe and compare their pharmacokinetic properties. (i) The PatentScope database of the World Intellectual Property Organization was searched for relevant English-language patent applications; (ii) Pharmacokinetic data were extracted, collated and analysed; (iii) PubMed was searched using Boolean search query '(nasal OR intranasal OR nose OR buccal OR sublingual) AND naloxone AND pharmacokinetics'. Five hundred and twenty-two PatentScope and 56 PubMed records were identified: three published international patent applications and five peer-reviewed papers were eligible. Pharmacokinetic data were available for intranasal, sublingual, and reference routes. Highly concentrated formulations (10-40mgmL-1 ) had been developed and tested. Sublingual bioavailability was very low (1%; relative to intravenous). Non-concentrated intranasal spray (1mgmL-1 ; 1mL per nostril) had low bioavailability (11%). Concentrated intranasal formulations (≥10mgmL-1 ) had bioavailability of 21-42% (relative to intravenous) and 26-57% (relative to intramuscular), with peak concentrations (dose-adjusted Cmax =0.8-1.7ngmL-1 ) reached in 19-30min (tmax ). Exploratory analysis identified intranasal bioavailability as associated positively with dose and negatively with volume. We find consistent direction of development of intranasal sprays to high-concentration, low-volume formulations with bioavailability in the 20-60% range. These have potential to deliver a therapeutic dose in 0.1mL volume. [McDonald R, Danielsson Glende Ø, Dale O, Strang J. International patent applications for non-injectable naloxone for opioid overdose reversal: Exploratory search and retrieve analysis of the PatentScope database. Drug Alcohol Rev 2017;00:000-000].

Pharmacokinetics of concentrated naloxone nasal spray over first 30 minutes post-dosing: analysis of suitability for opioid overdose reversal

Lack of non-injectable naloxone formulations has impeded widespread take-home provision for the prevention of heroin/opioid overdose deaths. For non-injectable formulations that are finally being investigated, rapid onset of action and sufficient bioavailability will be vital. We present analysis of data from a study of concentrated naloxone nasal spray formulations. Our aims are: to assess (1) pharmacokinetic properties and (2) suitability for overdose reversal in terms of naloxone absorption within 30minutes post-dosing. Open-label, randomized, four-way cross-over Latin-square pharmacokinetic study of naloxone administration by three routes: intranasal at two doses (8mg/0.4ml, 16mg/0.4ml) versus sublingual (16mg/ml) versus intravenous reference (1mg/ml). Clinical Pharmacology Unit at The Ohio State University (Columbus, OH, USA). Twelve healthy volunteers (age 20-41; seven female). From blood plasma naloxone concentrations, (1) standard pharmacokinetic parameters, including maximum plasma concentration (Cmax ) and mean absolute bioavailability (F%, relative to intravenous injection), were determined; as well as (2) partial area under the curve (AUC) values, tmax (time to maximum plasma concentration) and t50% (time to 50% of maximum plasma concentration) as measures of early absorption. (1) Bioavailability was F%=25-28% for intranasal naloxone. Sublingual had low bioavailability (F%=2%) and was not considered further. Mean Cmax values for 8mg (12.83ng/ml) and 16mg (18.25ng/ml) intranasal exceeded 1mg intravenous (9.64ng/ml) naloxone. (2) Following intranasal administration, t50% was reached within 8minutes and tmax within 20minutes. Mean naloxone absorption from dosing to 30minutes (AUC30 ) was greater following 8mg (4.17h×ng/ml) and 16mg (5.91h×ng/ml) intranasal than following 1mg intravenous (1.70h×ng/ml) administration. Concentrated naloxone nasal spray has a promising pharmacokinetic profile, with substantial bioavailability. Its early absorption time-course suggests that concentrated nasal naloxone is suitable for emergency administration in the community, where rapid restoration of respiratory function is essential for opioid overdose reversal.

Naloxone rescheduling in Australia: Processes, implementation and challenges with supply of naloxone as a 'pharmacist only' over-the-counter medicine.

Numerous studies and systematic reviews have concluded that naloxone for take-home use is an effective intervention to reduce overdose morbidity and mortality, with few side effects and no abuse potential. One barrier to supply is that naloxone has traditionally been a prescription medication. In May 2015, the Therapeutic Goods Administration of Australia announced the intention to down-schedule naloxone when used for the treatment of opioid overdose, enabling sale in pharmacies without a prescription. The aim of this article is to describe process of rescheduling of naloxone and some of the challenges observed. We describe the process of rescheduling from initial proposal development to gaining support and submissions from a range of individuals and professional bodies to support this change. The implications of the change, particularly for pharmacy supply of naloxone, are discussed, including next steps to facilitate implementation of this change in the Australian context. A submission to reschedule naloxone was successfully instigated by a member of the public. The change may help remove access barriers to naloxone by allowing pharmacist supply. Cost, pharmacist training, existing naloxone formulation, presentation and packaging remain challenges to address. Naloxone down-scheduling has opened up an additional way to supply naloxone through community pharmacy. Further expansion of naloxone availability may be achieved through addressing cost as a barrier, and making naloxone more widely accessible through needle syringe programs, and other services that do not have medical staff.