Nasal Spray Research Articles

Anti-SARS-CoV-2 antibodies in a nasal spray efficiently block viral transmission between ferrets

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread in the population. We recently reported the production of bovine colostrum-derived antibodies that can neutralize the virus. These have been formulated into a nasal spray. The immunoglobulin preparation is capable of blocking interaction of the trimeric spike protein (Tri S) of SARS-CoV-2 with the cellular receptor angiotensin-converting enzyme 2 (ACE2), entry of a pseudovirus carrying the Tri S into ACE2 over-expressing human embryonic kidney (HEK) cells, and entry of the virus into live Vero E6 cells. Using an ELISA assay, we demonstrate here that this holds true for different SARS-CoV-2 variants of concern. Using the ferret transmission model, we show that the nasal spray formulation of anti-SARS-CoV-2 immunoglobulins efficiently blocks transmission of SARS-CoV-2 from infected to uninfected ferrets. The results indicate that the use of the nasal spray in humans can add an effective additional layer of protection against the virus, and might be applicable for other viruses of the upper respiratory tract.

Periodontitis is associated with impaired olfactory function: Aclinical study.

To explore the association between periodontitis and olfactory disorders. Clinical data were collected from 198 individuals between the ages of 18 and 60 years living in Denmark. The exposure was periodontitis, and the outcome was olfactory function (Threshold, Discrimination, Identification - TDI score), both measured clinically. Covariates included sex, age, education level, income, usage of nasal spray, tongue coating, halitosis, xerostomia, smoking, and history of COVID-19. Structural equation modeling was used to estimate the association between periodontitis and olfactory function. Periodontitis was defined using the AAP/EFP classification and dichotomized into "no" (healthy subjects) and "yes" (Stages I, II, and III). Olfactory function was treated as a one-factor latent variable, including the different olfactory scores. In addition, extra models were performed considering each olfactory component as a separate outcome and the TDI Global Score. The results showed that periodontitis was associated with a lower olfactory function [standardized coefficient (SC) -0.264, 95% CI -0.401, -0.118]. Additionally, periodontitis was also associated with a lower olfactory Threshold (odorant concentration required for detection) (SC -0.207, 95% CI -0.325, -0.089), Discrimination (ability to discriminate between odorants) (SC -0.149, 95% CI -0.270, -0.027), Identification (ability to identify odorants) scores (SC -0.161, 95% CI -0.277, -0.045), and TDI Global Score (SC -0.234, 95% CI -0.370, -0.099). This study suggests that periodontitis is associated with olfactory impairment.

Development of neffy, an Epinephrine Nasal Spray, for Severe Allergic Reactions.

Epinephrine autoinjectors (EAIs) are used for the treatment of severe allergic reactions in a community setting; however, their utility is limited by low prescription fulfillment rates, failure to carry, and failure to use due to fear of needles. Given that delayed administration of epinephrine is associated with increased morbidity/mortality, there has been a growing interest in developing needle-free, easy-to-use delivery devices. neffy (epinephrine nasal spray) consists of three Food and Drug Administration (FDA)-approved components: epinephrine, Intravail A3 (absorption enhancer), and a Unit Dose Spray (UDS). neffy's development pathway was established in conjunction with the FDA and the European Medicines Agency and included multiple clinical trials to evaluate pharmacokinetic and pharmacodynamic responses under a variety of conditions, such as self-administration and allergic and infectious rhinitis, as well as an animal anaphylaxis model of severe hypotension, where neffy demonstrated a pharmacokinetic profile that is within the range of approved injection products and a pharmacodynamic response that is as good or better than injections. The increased pulse rate (PR) and blood pressure (BP) observed even one minute following the administration of neffy confirm the activation of α and β adrenergic receptors, which are the key components of epinephrine's mechanism of action. The results suggest that neffy will provide a safe and effective needle-free option for the treatment of severe allergic reactions, including anaphylaxis.

Association Between Cost Sharing and Naloxone Prescription Dispensing

Increasing access to naloxone (an opioid antagonist that can reverse overdose) could slow the US opioid epidemic. Prior studies suggest cost sharing may be a barrier to dispensing of naloxone prescriptions, but these studies were limited by their cross-sectional designs and use of databases that do not capture prescriptions that are not filled (abandoned). To evaluate the association between cost sharing and naloxone prescription abandonment (nondispensing of naloxone prescriptions). This cross-sectional, regression discontinuity analysis exploited the fact that deductibles typically reset at the beginning of the year in commercial and Medicare plans. The included data were derived from the 2020-2021 IQVIA Formulary Impact Analyzer (a pharmacy transactions database that represents 63% of prescriptions at US pharmacies). The analysis included claims for naloxone nasal spray among commercially insured patients and Medicare patients that occurred during the 60 days before January 1, 2021, through 59 days after January 1, 2021. Cost sharing, which is defined as the amount patients would have to pay to fill prescriptions. Local linear regression models were used to assess for abrupt changes in cost sharing and the probability of prescription abandonment on January 1, 2021. To estimate the association between cost sharing and prescription abandonment, a fuzzy regression discontinuity analysis was conducted. These analyses included naloxone claims for 71 306 commercially insured patients and 101 706 Medicare patients (40 019 [56.1%] and 61 410 [60.4%], respectively, were female). The commercially insured patients and Medicare patients accounted for 73 311 and 106 076 naloxone claims, respectively. On January 1, 2021, the mean cost sharing per claim increased by $15.0 (95% CI, $13.8-$16.2) for commercially insured patients and increased by $12.3 (95% CI, $10.9-$13.6) for Medicare patients and the probability of abandonment increased by 4.7 (95% CI, 3.2-6.2) percentage points and 2.8 (95% CI, 1.6-4.1) percentage points, respectively. The results from the fuzzy regression discontinuity analysis suggest a decision by commercial and Medicare plans to increase naloxone cost sharing by $10 would be associated with percentage-point increases of 3.1 (95% CI, 2.2-4.1) and 2.3 (95% CI, 1.4-3.2), respectively, in the probability of abandonment. The elimination of cost sharing might be associated with increased naloxone dispensing to commercially insured and Medicare patients.

Intranasal Tapentadol Versus Intravenous Paracetamol for Postoperative Analgesia in Lower Limb Orthopaedic Surgeries Under Spinal Anaesthesia: A Single Blind RCT.

We aimed to compare the analgesic effectiveness of intranasal tapentadol nasal spray 44.5mg and intravenous (IV) paracetamol 1gm during the postoperative period in patients undergoing lower limb orthopedic surgeries under spinal anesthesia. This prospective, randomized, single-blind clinical trial was carried out in a tertiary care teaching hospital. Patients aged between 18 and 60 years of physical status ASA grade 1-3 were included in the study. Postoperative pain scores were measured using the visual analog scale (VAS) in centimeters (cm) every 12 hours in 37 patients per group. The patients were administered either intranasal tapentadol or IV paracetamol every 6 hours for 72 hours, beginning 3 hours after surgery. There was a significant group by intervention effect favoring intranasal tapentadol, suggesting a greater reduction in VAS pain scores after the intervention at 72 hours (estimate: -1.58 cm; SE:0.2; P<0.001). Group by time effect for all the measured time frames, except for 36 hours, favored intranasal tapentadol with estimated values for greater reduction in VAS pain scores ranging from -0.8 cm to -1.6 cm. The results of the present study suggests that intranasal tapentadol results in a greater reduction of postoperative pain compared with IV paracetamol in lower limb orthopedic surgeries. The ease of administration of tapentadol may make it a preferred option over IV paracetamol in such surgeries.

Whole body physiology model to simulate respiratory depression of fentanyl and associated naloxone reversal

BackgroundOpioid use in the United States and abroad is an endemic part of society with yearly increases in overdose rates and deaths. In response, the use of the safe and effective reversal agent, naloxone, is being fielded and used by emergency medical technicians at a greater rate. There is evidence that repeated dosing of a naloxone nasal spray is becoming more common. Despite this we lack repeated dosing guidelines as a function of the amount of opiate the patient has taken.MethodsTo measure repeat dosing guidelines, we construct a whole-body model of the pharmacokinetics and dynamics of an opiate, fentanyl on respiratory depression. We then construct a model of nasal deposition and administration of naloxone to investigate repeat dosing requirements for large overdose scenarios. We run a single patient through multiple goal directed resuscitation protocols and measure total naloxone administered.ResultsHere we show that naloxone is highly effective at reversing the respiratory symptoms of the patient and recommend dosing requirements as a function of the fentanyl amount administered. We show that for increasing doses of fentanyl, naloxone requirements also increase. The rescue dose displays a nonlinear response to the initial opioid dose. This nonlinear response is largely logistic with three distinct phases: onset, rapid acceleration, and a plateau period for doses above 1.2 mg.ConclusionsThis paper investigates the total naloxone dose needed to properly reverse respiratory depression associated with fentanyl overdose. We show that the current guidelines for a rescue dose may be much lower than required.

In Situ Gelling Behavior and Biopharmaceutical Characterization of Nano-Silver-Loaded Poloxamer Matrices Designed for Nasal Drug Delivery.

A combination of Poloxamer 407 (P407) and hydroxypropyl methylcellulose (HPMC) hydrosols is proposed as an in situ thermo-gelling vehicle for the nasal drug delivery of chlorhexidine-silver nanoparticles conjugates (SN-CX). Optimization of the formulation was carried out by applying varying ratios of P407 and HPMC in the presence and absence of SN-CX so that gelation would occur in the temperature range of the nasal cavity (30-34 °C). Mechanisms for the observed gelation phenomena were suggested based on viscosimetry, texture analysis, and dynamic light scattering. Tests were carried out for sprayability, washout time, in vitro drug release, ex vivo permeation, and antimicrobial activity. When applied separately, HPMC was found to lower the P407 gelation temperature (Tg), whereas SN-CX increased it. However, in the presence of HPMC, SN-CX interfered with the P407 micellar organization in a principally contrasting way while leading to an even further decrease in Tg. SN-CX-loaded nasal formulations composed of P407 16% and HPMC 0.1% demonstrated a desired gelation at 31.9 °C, good sprayability (52.95% coverage of the anterior nasal cavity), mucoadhesion for 70 min under simulated nasal clearance, expedient release and permeation, and preserved anti-infective activity against seasonal Influenza virus and beta-coronavirus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus and other pathogens. Our findings suggest that the current development could be considered a potential formulation of a protective nasal spray against respiratory infections.

Concentration-QTc and cardiac safety analysis of single and multiple zavegepant nasal spray doses in healthy participants to support approval.

Zavegepant is a novel gepant administered as a nasal spray approved in the United States at a 10 mg dose for the acute treatment of migraine with or without aura in adults. The cardiovascular safety of zavegepant nasal spray was assessed in both single-ascending dose (SAD) and multiple-ascending dose (MAD) studies in healthy participants. The SAD study included 72 participants (54 active/18 placebo) who received 0.1-40 mg zavegepant or placebo. The MAD study included 72 participants (56 active/16 placebo) who received 5-40 mg zavegepant or placebo for 1-14 days. Plasma zavegepant pharmacokinetics and electrocardiographic (ECG) parameters (Fridericia-corrected QT interval [QTcF], heart rate, PR interval, ventricular depolarization [QRS], T-wave morphology, and U-wave presence) were analyzed pre- and post-zavegepant administration. Using pooled data from the SAD and MAD studies, the relationship between time-matched plasma zavegepant concentrations and QTc interval was assessed using a linear mixed-effects model to evaluate the potential for QTc interval prolongation. Results showed that single and multiple doses of zavegepant had no significant impact on ECG parameters versus placebo, and there was no concentration-dependent effect on QTcF interval. The estimated slope of the plasma zavegepant concentration-QTcF model was -0.053 ms per ng/mL with a 90% confidence interval of -0.0955 to -0.0110 (p = 0.0415), which is not considered clinically meaningful. At doses up to four times the recommended daily dose, zavegepant does not prolong the QT interval to any clinically relevant extent.

Cosmetic Changes in Eyes Induced by Over-the-Counter Nasal Spray

Cosmetic Changes in Eyes Induced by Over-the-Counter Nasal Spray

SA29 Motivations and Barriers for Psychiatric Practice Adoption of Esketamine Nasal Spray for Treatment-Resistant Depression in the United States

SA29 Motivations and Barriers for Psychiatric Practice Adoption of Esketamine Nasal Spray for Treatment-Resistant Depression in the United States

Evaluation of Strategies to Enhance Community-Based Naloxone Distribution Supported by an Opioid Settlement

Many US states are substantially increasing community-based naloxone distribution, supported in part through settlements from opioid manufacturers and distributors. To evaluate the potential impact of increased naloxone availability on opioid overdose deaths (OODs) and explore strategies to enhance this impact by integrating interventions to address solitary drug use. This decision analytical modeling study used PROFOUND (Prevention and Rescue of Fentanyl and Other Opioid Overdoses Using Optimized Naloxone Distribution Strategies), a previously published simulation model, to forecast annual OODs between January 2023 and December 2025. The simulated study population included individuals from Rhode Island who misused opioids and stimulants and were at risk for opioid overdose. The study modeled expanded naloxone distribution supported by the state's opioid settlement (50 000 naloxone nasal spray kits each year). Two approaches to expanding naloxone distribution were evaluated: one based on historical spatial patterns of naloxone distribution (supply-based approach) and one based on the spatial distribution of individuals at risk (demand-based approach). In addition, hypothetical interventions to enhance the likelihood of witnessed overdoses in private or semiprivate settings were considered. Annual number of OODs and ratio of fatal to nonfatal opioid overdoses. Modeling results indicated that distributing more naloxone supported by the state's opioid settlement could reduce OODs by 6.3% (95% simulation interval [SI], 0.3%-13.7%) and 8.8% (95% SI, 1.8%-17.5%) in 2025 with the supply-based and demand-based approaches, respectively. However, increasing witnessed overdoses by 20% to 60% demonstrated greater potential for reducing OODs, ranging from 8.5% (95% SI, 0.0%-20.3%) to 24.1% (95% SI, 8.6%-39.3%). Notably, synergistic associations were observed when combining both interventions: increased naloxone distribution with the 2 approaches and a 60% increase in witnessed overdoses could reduce OODs in 2025 by 33.5% (95% SI, 17.1%-50.4%) and 37.4% (95% SI, 19.6%-56.3%), respectively. These findings suggest that interventions to address solitary drug use are needed to maximize the impact of continued efforts to increase community-based naloxone distribution, which may be particularly important for jurisdictions that have strong community-based naloxone distribution programs.

Health Threat in the Tanning Trend

Self enhancement products have become increasingly popular options to achieve tanning in the pursuit of darker complexion. This practice is relatively popular among both men and women for aesthetic purposes. Melanotan-I and melanotan-II are synthetic alpha-melanocyte stimulating hormone (α-MSH) analogues that stimulate tanning, which are available in two forms, injectable and nasal spray, and can be purchased via online portals and media outlets. The health consequences of these products range from minor to acute and chronic clinical outcomes. Sunless tanning products are alternatively, perceived as “healthy alternatives” to sunbathing, however, no consistent data on their safety is standardized.

A real-world study examining the impact of esketamine nasal spray in people living with major depressive disorder in Australia and New Zealand

IntroductionEsketamine has been approved in Australia and New Zealand as a third-line antidepressant treatment for treatment resistant depression. This study describes changes in quality of life, depressive symptoms and productivity in participants treated with esketamine in real-world settings. MethodsParticipants were recruited from an esketamine early access program and had not responded to two or more different antidepressants and not received neurostimulation for their current depressive episode. Participants received esketamine for 16 weeks or longer. Data collected included Assessment of Quality-of-Life scale (AQoL-8D), Hamilton Depression Rating Scale (HAM-D) and Work Productivity Activity Index (WPAI). ResultsParticipants (n = 105) had a mean age of 38.7 years (standard deviation (SD) = 14.6) and were predominantly female (59.0%). The mean duration of major depressive disorder was 7.2 years (SD = 4.2) and almost half of participants had been treated with 3–5 prior therapies. After 16-weeks on esketamine, participants showed improvement of greater than 10% across all dimensions of AQoL-8D, HAM-D scores decreased 8.0 points, and activity impairment decreased 20.4% as measured by WPAI. LimitationsThis was a non-randomized and unblinded study and may have selection and reporting bias. The population was not necessarily representative of the broader Australian and New Zealand population. It is not possible to determine if the results will be sustained or changed if participants received treatment for longer. ConclusionsEsketamine early access program participants, who were a real-world cohort with extensive prior treatment, showed clinically significant improvements in quality of life, depression severity and productivity after 16-weeks on treatment.

Therapeutic Effects of Capsaicin on Pain Management

Pain is an undesirable sensory experience that occurs from the noisome stimulus, it becomes a warning sign of an upcoming disease or existing disease thereby signaling immediate attention. There exists a variety of pharmacological and non-pharmacological methods to alleviate pain, with their own effects and impacts on health. The natural herb capsicum, used in most families as a spice is also found to have the therapeutic effects of for treating cardiovascular disorders, respiratory issues, gastrointestinal problems, urological disorders, cancer, diabetic peripheral neuropathy, obesity and pain reduction, especially in osteoarthritis and rheumatoid arthritis. It acts as a counter-irritant for various conditions like rheumatism, lumbago and neuralgia. It reduces pain by aiding in the depletion of substance-P and increases the activation of intracellular calcium by activating the calcium channel. The stimulation of transient receptor potential vanilloid 1 (TRPV1) causes effects like analgaesia, anti-infectious, anti-carcinogenic and antioxidant. It is permissible to use capsaicin in low concentrations such as in creams, lotions, gel patches and nasal sprays. High-concentration capsaicin is available in the form of oral formulations, intradermal, subcutaneous and intravenous. Capsaicin is mostly available in topical form, in many concentrations such as 0.025%, 0.0355%, 0.075% and 0.10%. It has been permitted to use capsaicin to the maximum concentration of 8%. Capsaicin is safe to use even in pregnancy, lactation, children and adolescents but is contraindicated for children less than 2 years old as well as for people with bleeding disorders..

Understanding Fentanyl A Synthetic Piperidine Opioid Drug: Deciphering the Pain-Relieving Double-Edged Sword

Fentanyl is a synthetic opioid analgesic that has revolutionized pain management in various medical contexts. It has remarkable potency and effectiveness in managing severe pain, owing to its unique mechanisms of action on opioid receptors and modulation of pain perception. Fentanyl can be administered through various routes, such as transdermal patches, intravenous injections, lozenges, and nasal sprays. It is commonly utilized for post-operative pain management, cancer-related pain, and palliative care. However, fentanyl also poses significant risks of addiction, abuse, and overdose. The alarming increase in fentanyl-related fatalities underscores the importance of understanding proper dosage, monitoring patients closely, and implementing harm reduction strategies. Furthermore, the responsible use of fentanyl requires comprehensive patient assessment, individualized treatment plans, and the active involvement of healthcare providers in educating patients and obtaining informed consent. The article also discusses ongoing research efforts to improve fentanyl’s safety profile while maintaining its efficacy. These include emerging technologies, potential formulations, and alternative pain management strategies that could help reduce the dependence on fentanyl and prevent its adverse effects. The article provides a balanced perspective on fentanyl, emphasizing the balance between its pain-relieving benefits and the potential risks it poses. It also reinforces the significance of responsible prescribing, vigilant monitoring, and patient education to ensure optimal pain relief and patient safety.

Nicotine flux and pharmacokinetics-based considerations for early assessment of nicotine delivery systems

In the past few years, technological advancements enabled the development of novel electronic nicotine delivery systems (ENDS). Several empirical measures such as “nicotine flux” are being proposed to evaluate the abuse liability potential of these products. We explored the applicability of nicotine flux for clinical nicotine pharmacokinetics (PK) and 52-week quit success from cigarettes for a wide range of existing nicotine delivery systems. We found that the differences in nicotine flux for various nicotine delivery systems are not related to changes in PK, as nicotine flux does not capture key physiological properties such as nicotine absorption rate. Further, the 52-week quit success and abuse liability potential of nicotine nasal sprays (high nicotine flux product), and nicotine inhalers (nicotine flux similar to ENDS) are low, suggesting that nicotine flux is a poor metric for the assessment of nicotine delivery systems. PK indices are more dependable for characterizing nicotine delivery systems, and a nicotine plasma CmaxTmax > 1 could improve 52-week quit success from cigarettes. However, a single metric may be inadequate to fully assess the abuse liability potential of nicotine delivery systems and needs to be further studied. A combination of in vitro and in silico approaches could potentially address the factors influencing the inhaled aerosol dosimetry and resulting PK of nicotine to provide early insights for ENDS assessments. Further research is required to understand nicotine dosimetry and PK for ad libitum product use, and abuse liability indicators of nicotine delivery systems. This commentary is intended to (1) highlight the need to think beyond a single empirical metric such as nicotine flux, (2) suggest potential PK-based metrics, (3) suggest the use of in vitro and in silico tools to obtain early insights into inhaled aerosol dosimetry for ENDS, and (4) emphasize the importance of considering comprehensive clinical pharmacology outcomes to evaluate nicotine delivery systems.

Rose geranium in sesame oil nasal spray to improve nasal vestibulitis symptoms: a randomized controlled trial.

The purpose of this phase III randomized double-blinded controlled trial was to investigate the efficacy of a rose geranium in sesame oil (RG) nasal spray compared with an isotonic saline (IS) nasal spray for alleviating nasal vestibulitis symptoms among patients undergoing chemotherapy. Patients undergoing active chemotherapy who reported associated nasal symptoms were randomized 1:1 to receive RG or IS, administered twice daily for 2 weeks. Consenting participants completed nasal symptom questionnaires at baseline and then weekly while on treatment. The proportion of patients experiencing improvements in their nasal symptoms 2weeks after initiating the nasal spray, using a six-point global impression of change score, was estimated within and between each randomized arm, and compared between arms, using Fisher's exact test. The estimated odds ratio was determined (95% confidence interval). One hundred and six patients consented to this study; 43 participants in the RG arm and 41 in the IS arm were evaluable for the primary endpoint. Participants had a mean age of 57.8years (SD 13.9). Demographic characteristics and baseline nasal symptoms were similar between arms. Of the evaluable participants who received RG, 67.4% reported improved nasal symptoms, compared with 36.6% of the participants who received IS (P = 0.009). Adverse events were sparse and did not differ between arms. Rose geranium in sesame oil significantly improves nasal vestibulitis symptoms among patients undergoing chemotherapy. NCT04620369.

Comparison of oral versus intranasal methylcobalamin in patients of tinnitus

Background: Tinnitus is perception of sound in the absence of an external auditory stimulus. It is an experience that originates from a cause or trigger in the cochlea, brainstem or at higher centres. Methods: A randomized, double-blinded pilot study was conducted, wherein a total of 64 patients were enrolled. Of which 32 were considered as Group A (oral methylcobalamin was administered) and 32 in Group B (intranasal methylcobalamin was administered). Group A patients enrolled randomly received oral methylcobalamin therapy (tablet methylcobalamin 500 mcg tablet once a day for a period of 6 weeks). Group B patients enrolled randomly received intranasal methylcobalamin treatment (nasal spray 500 mcg per day) for a period of 6 weeks. Results: A sum of 19 patients of the total patients included in the study were found to be Vitamin B12 deficient that is 42.1% were considered to be Vitamin B12 deficient when the normal levels were considered to be 250 pg/ml, which could be considered to be a significantly high prevalence. Patients having Vitamin B12 deficiency showed improvement in visual analogue scale score after vitamin B12 therapy. Conclusions: Supplementation of Vitamin B12 in vitamin B12 deficient patients having tinnitus has shown symptomatic improvement. However, no significant improvement in visual analogue scale scores in patients without B12 deficiency was observed. There was improvement in VAS in cobalamin-deficient patients receiving Vitamin B12 weekly for 6 weeks.

Diazepam nasal spray administration is effective to control seizure clusters irrespective of time of day

IntroductionNeurologic circadian influences, including sleep/wake transitions, processes (e.g., hormonal variation), and behavioral patterns (e.g., consumption of food and oral medications), may affect seizure patterns. Specific circadian patterns of seizures have been reported depending on type, onset location, and severity; however, data on patterns for patients with seizure clusters and effectiveness of rescue therapy by time of day are limited.MethodsWe conducted post hoc analyses using patient diary data from the phase 3 safety study of diazepam nasal spray, which is indicated for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years. Patients were administered age- and weight-based doses; second doses could be administered if needed to control a seizure cluster. We assessed clock timing of seizure-cluster onset along with second-dose use as a proxy for effectiveness. Treatment-emergent adverse events were recorded.ResultsSeizure-cluster onset was observed to be generally highest during mornings and late evenings and lowest in the early evening and middle of the night. Second-dose use was not consistently associated with a specific time of day. The safety profile was consistent with that expected from previous studies of diazepam nasal spray.ConclusionThese results suggest that diazepam nasal spray can be effectively administered at any time of day.

Accessibility of Naloxone in Pharmacies Registered Under the Illinois Standing Order.

To expand access to naloxone, the state of Illinois implemented a standing order allowing registered pharmacies to dispense the drug without an individual prescription. To participate under the standing order, pharmacies were required to opt in through a formal registration process. In our study we aimed to evaluate the availability and price of naloxone at registered pharmacies. This was a prospective, de-identified, cross-sectional telephone survey. Trained interviewers posed as potential customers and used a standardized script to determine the availability of naloxone between February-December, 2019. The primary outcome was defined as a pharmacy indicating it carried naloxone, currently had naloxone in stock, and was able to dispense it without an individual prescription. Of 948 registered pharmacies, 886 (93.5%) were successfully contacted. Of those, 792 (83.4%) carried naloxone, 659 (74.4%) had naloxone in stock, and 472 (53.3%) allowed purchase without a prescription. Naloxone nasal spray (86.4%) was the formulation most commonly stocked. Chain pharmacies were more likely to carry naloxone (adjusted odds ratio [aOR] 3.16, 95% confidence interval [CI] 1.97-5.01, P < 0.01) and have naloxone in stock (aOR 2.72, 95% CI 1.76-4.20, P < 0.01), but no more likely to dispense it without a prescription. Pharmacies in higher population areas (aOR 0.99, 95% CI 0.99-0.99, P < 0.05) and rural areas adjacent to metropolitan areas (aOR 0.5, 95% CI 025-0.98, P < 0.05) were less likely to have naloxone available without a prescription. Associations of naloxone availability based on other urbanicity designations, overdose count, and overdose rate were not significant. Among pharmacies in Illinois that formally registered to dispense naloxone without a prescription, the availability of naloxone remains limited. Additional interventions may be needed to maximize the potential impact of a statewide standing order.