Nasal Spray Research Articles

Treatment Patterns, Acute Healthcare Resource Use, and Costs of Patients with Treatment-Resistant Depression Completing Induction Phase of Esketamine in the United States.

This study aimed to understand treatment patterns, acute healthcare use, and cost patterns among adults with treatment-resistant depression (TRD) who completed induction treatment with esketamine nasal spray in the United States (US). Per label, induction is defined as administration twice a week for 4 weeks, after which maintenance is started on a weekly basis for 4 weeks, and thereafter, patients are treated weekly or bimonthly. Adults with one or more esketamine claim (index date) on or after March 5, 2019 were selected from Optum's de-identified Clinformatics® Data Mart Database (January 2016-June 2022). Before the index date, patients had evidence of TRD and ≥12 months of continuous insurance eligibility (baseline period). Patients with eight or more esketamine treatment sessions were included in the main cohort. A subgroup included patients with one or more baseline mental health (MH)-related inpatient (IP) admission or emergency department (ED) visit (i.e., prior acute healthcare users). Treatment patterns were described during the follow-up period (index date until earliest of end of insurance eligibility or data); acute healthcare (i.e., IP and ED) resource use and costs (2021 US dollars) were reported during the baseline and follow-up periods. Of the 322 patients in the main cohort, 111 comprised the subgroup of prior acute healthcare users. During the follow-up period, mean time from index date to eighth esketamine session was 73.2days in the main cohort and 78.8days in the subgroup (per label, 28days). Further, 75.2% of the main cohort and 73.9% of the subgroup completed four or more esketamine maintenance sessions following induction. In the main cohort, mean all-cause acute healthcare costs per patient per month (PPPM) decreased from baseline ($837) to follow-up ($770). Similar reductions were observed for mean MH-related acute healthcare costs PPPM (baseline $648, follow-up $577). In the subgroup, mean all-cause acute healthcare costs PPPM also decreased (baseline $2323, follow-up $1423), driven by mean MH-related acute healthcare costs PPPM (baseline $1880, follow-up $1139). Mean all-cause acute healthcare use per ten patients per month remained largely stable from baseline to follow-up in the main cohort (IP days: baseline 2.24, follow-up 2.13; ED visits: baseline 1.33, follow-up 1.45) and decreased in the subgroup (IP days: baseline 6.38, follow-up 4.56; ED visits: baseline 2.58, follow-up 2.41). Trends in mean MH-related acute healthcare use were similar. Patients generally required more time than label recommendation to complete esketamine induction treatment, and most went on to have 12 or more esketamine sessions. Completion of induction treatment correlated with reductions in mean all-cause and MH-related acute healthcare costs. Larger reductions were seen in the subgroup of prior acute healthcare users.

Barriers to Esketamine Nasal Spray Treatment Among Adults With Treatment-Resistant Depression.

Barriers to Esketamine Nasal Spray Treatment Among Adults With Treatment-Resistant Depression.

How side effects can improve treatment efficacy: a randomized trial.

While treatment side effects may adversely impact patients, they could also potentially function as indicators for effective treatment. In this study, we investigated whether and how side effects can trigger positive treatment expectations and enhance treatment outcomes. In this preregistered trial (DRKS00026648), 77 healthy participants were made to believe that they will receive fentanyl nasal sprays before receiving thermal pain in a controlled experimental setting. However, nasal sprays did not contain fentanyl, rather they either contained capsaicin to induce a side effect (mild burning sensation) or saline (inert). After the first session, participants were randomized to two groups and underwent functional magnetic resonance imaging (fMRI). One group continued to believe that the nasal sprays could contain fentanyl while the other group was explicitly informed that no fentanyl was included. This allowed for the independent manipulation of the side effects and the expectation of pain relief. Our results revealed that nasal sprays with a side effect lead to lower pain than inert nasal sprays without side effects. The influence of side effects on pain was dependent on individual beliefs about how side effects are related to treatment outcome, as well as on expectations about received treatment. FMRI data indicated an involvement of the descending pain modulatory system including the anterior cingulate cortex and the periaqueductal gray during pain after experiencing a nasal spray with side effects. In summary, our data show that mild side effects can serve as a signal for effective treatment thereby influencing treatment expectations and outcomes, which is mediated by the descending pain modulatory system. Using these mechanisms in clinical practice could provide an efficient way to optimize treatment outcome. In addition, our results indicate an important confound in clinical trials, where a treatment (with potential side effects) is compared to placebo.

Successful treatment of a Morbihan's disease patient after a therapeutic challenge: A case report and comprehensive literature review

AbstractMorbihan's disease is a rare condition characterized by chronic facial edema. While its exact cause is unknown, it is thought to involve local cutaneous vascularization and lymphatic drainage imbalance. Traditional treatment options are often ineffective, and no established efficient treatment exists. We present a case study of a 17‐year‐old male with Morbihan's syndrome who showed resistance to traditional treatments but responded well to a combination of cromolyn sodium nasal spray and oral montelukast after histopathology revealed hyperplasia of plasma cells and mast cells. This combination has not been used before for Morbihan's syndrome. Our review of the literature also provides insight for clinicians seeking to manage this condition.

Managing children with frequent respiratory infections and associated wheezing: a preliminary randomized study with a new multicomponent nasal spray.

Preschoolers frequently have respiratory infections (RIs), which may cause wheezing in some subjects. Type 2 polarization may favor increased susceptibility to RIs and associated wheezing. Non-pharmacological remedies are garnering increasing interest as possible add-on therapies. The present preliminary study investigated the efficacy and safety of a new multi-component nasal spray in preschoolers with frequent RIs and associated wheezing. Some preschoolers with these characteristics randomly took this product, containing lactoferrin, dipotassium glycyrrhizinate, carboxymethyl-beta-glucan, and vitamins C and D3 (Saflovir), two sprays per nostril twice daily for 3 months. Other children were randomly treated only with standard therapy. Outcomes included the number of RIs and wheezing episodes, use of medications, and severity of clinical manifestations. Preschoolers treated add-on with this multicomponent product experienced fewer RIs and used fewer beta-2 agonists than untreated children (P = 0.01 and 0.029, respectively). This preliminary study demonstrated that a multicomponent product, administered add-on as a nasal spray, could reduce the incidence of RIs and use of symptomatic drugs for relieving wheezing in children.

Randomized trial of pharmacokinetic and pharmacodynamic effects of 13.2 mg intranasal epinephrine treatment in congestion

BackgroundNasal congestion could affect the absorption of an epinephrine nasal spray (ENS). ObjectiveTo compare the pharmacokinetics of 13.2 mg ENS with nasal congestion vs without congestion and vs intramuscular (IM) treatments. MethodsThis phase I, open-label, 4-period randomized crossover study enrolled 51 healthy adults with seasonal allergies into cohorts that received a single dose of 13.2 mg ENS (NDS1C; Bryn Pharma, Lebanon, New Jersey) administered as 2 consecutive sprays in either opposite nostrils (cohort 1) or the same nostril (cohort 2). Both cohorts received 13.2 mg ENS with and without nasal allergen challenge (NAC), 0.3 mg IM epinephrine by autoinjector, and 0.5 mg IM epinephrine by manual syringe (MS). ResultsThe ENS after NAC resulted in higher extent and peak exposures and more rapid time to maximum plasma concentration vs ENS without NAC and IM treatments. In cohort 1, the maximum observed baseline-adjusted epinephrine plasma concentration (pg/mL) of ENS with NAC, IM autoinjector, IM MS, or ENS without NAC was 458.0, 279.0, 364.2, and 270.1, respectively, and in cohort 2 was 436.3, 228.2, 322.3, and 250.8, respectively. The maximum observed baseline-adjusted epinephrine plasma concentration geometric mean ratio (90% CI) for ENS with NAC vs without NAC in cohort 1 was 170% (123%-234%), and in cohort 2 was 174% (115%-263%). In cohort 1, the rapid time to maximum plasma concentration was 15, 21, 45, and 25 minutes, respectively, and in cohort 2 was 18, 20, 45, and 20 minutes, respectively (P < .01 for ENS with NAC vs IM MS). The postdose mean heart rate and blood pressure remained stable and relatively similar to predose values regardless of plasma epinephrine concentration. Mild nausea and headache were the most common adverse events with ENS. ConclusionThe 13.2 mg ENS with congestion exhibited enhanced absorption vs IM treatments and ENS without congestion and seemed to be well tolerated. There was no clinically impactful relationship between pharmacodynamic effects and plasma epinephrine concentration.

In vitro evaluation of intersubject variability in pediatric intranasal drug delivery using nasal spray suspension products

Evaluation of the regional intranasal delivery of locally acting drugs in children is challenging. Anatomical nasal airway replicas potentially can provide a robust pre-clinical tool to test the performance of devices and formulations. However, there is often a challenge in identifying the nasal geometries that can reasonably be indicative of in vivo regional mass distribution of administered drug. This in vitro study was designed to investigate the regional intranasal drug delivery in 20 children, 2–11 years old (50% 2–6 years old and 50% female), using two commercially available suspension nasal spray products with different nozzle designs, plume characteristics, and active pharmaceutical ingredients. High-resolution computed tomography scans of the sinonasal region of pediatric human subjects with healthy nasal airways, reviewed and scored by a head and neck surgeon, were used to develop 20 three-dimensional (3D) replicas of the nasal airways. The 3D replicas were segmented into the two regions: anterior and posterior to the internal nasal valve (INV). They were then rapid prototyped in high clarity rigid plastic (Accura ClearVue). Each side of the septum of the 20 subjects was examined separately, resulting in 40 singular nasal cavities. A nozzle-specific spray tip holder was designed for each case to ensure consistent administration (insertion length, sagittal angle, and coronal angle) in all replicates. The wide range of posterior drug delivery observed in the forty geometries indicated significant intersubject variability in pediatric intranasal drug delivery. Three nasal geometries representing low, medium, and high levels of drug delivery to the target region, posterior to the INV, were chosen from the 40 nasal cavities. Our vision is that these three nasal geometries can potentially be beneficial in determining whether performance differences between test and reference nasal spray products are present that may affect their bioequivalence in children. They also may be useful when applied in parallel with similar adult nasal geometries, previously developed following a similar procedure, to provide additional insights into pediatric nasal drug delivery with innovator products in children in lieu of extending clinical studies to include pediatric subjects.

Varenicline Solution Nasal Spray for the Treatment of Dry Eye Disease Following LASIK.

The purpose of this study is to evaluate the use of a varenicline solution nasal spray (VNS) for reducing the signs and symptoms of dry eye following laser in situ keratomileusis (LASIK). Subjects electing to undergo LASIK were randomized to VNS (study group) or placebo/vehicle (control group) and initiated treatment with the nasal spray twice daily 28days prior to surgery with continued treatment for 84days following LASIK. After initiation of treatment, subjects were seen on the day of surgery and postoperatively on Days 1, 7, 28, 84 (3months) and 168 (6months). The primary outcome measure was the mean change in NEI-VFQ-25, a 25-item dry eye questionnaire, from baseline to 3months. The second primary outcome measure was the mean change in corneal fluorescein staining. Secondary outcome measures included evaluation of tear break-up time, Schirmer testing, tear osmolarity and eye dryness score (EDS). Twenty subjects were enrolled in each group and successfully underwent LASIK. Both groups demonstrated an improvement in the National Eye Institute Visual Function Questionnaire (NEI-VFQ) at 3months. The study group demonstrated improved corneal staining scores at months 1 and 3. Similarly, the study group demonstrated improvement in tear osmolarity scores versus the placebo group at the same time points. Although the study group was numerically greater than placebo for each time point for both corneal staining and tear osmolarity, the differences were not statistically significant for any primary or secondary outcome measures. VNS is a dry eye treatment option for patients following LASIK and may have potential benefit for patients hoping to avoid additional topical medications. The results were not statistically significant compared to placebo in this trial, and further investigation of the use of VNS following LASIK in a larger trial would be beneficial.

Ketamine and its enantiomers for depression: a bibliometric analysis from 2000 to 2023.

Ketamine has demonstrated rapid and sustained antidepressant effects, marking its emergence as an innovative treatment of depression. Despite the growing number of preclinical and clinical studies exploring the antidepressant effects of ketamine and its enantiomers, a comprehensive bibliometric analysis in this field has yet to be conducted. This study employs bibliometric methods and visualization tools to examine the literature and identify key topics related to the antidepressant effects of ketamine and its enantiomers. We sourced publications on the antidepressant effects of ketamine and its enantiomers from the Web of Science Core Collection (WOSCC) database, covering the period from 2000 to 2023. Tools such as VOSviewer, CiteSpace and the R package "bibliometrix" were utilized for visual analysis. The study included 4,274 publications, with a notable increase in publications peaking in 2022. Co-occurrence analysis highlighted two primary research focal points: the efficacy and safety of ketamine and its enantiomers in treating depression, and the mechanisms behind their antidepressant effects. In conclusion, this analysis revealed a significant increase in research on the antidepressant effects of ketamine and its enantiomers over the past two decades, leading to the approval of esketamine nasal spray for treatment-resistant depression. The rapid antidepressant effects of ketamine have spurred further studies into its mechanisms of action and the search for new antidepressants with fewer side effects.

Numerical study of the distribution of sprayed particle deposition in different human nasal cavity

This article numerically investigates the propagation of nasal sprayer particles to improve drug delivery through the nasal cavity. Topical nasal sprays are among the generally dictated therapeutic agents for sinus disorders in humans. However, the inconsistency of instructions indicates a lack of definitive knowledge of the best methods for nebulizing drugs. This study suggested nasal spray angles that could improve local drug delivery to the affected area compared to common spray methods. In this study, various particle diameters and aerosol flow angles are examined to evaluate the optimal efficiency of drug supply into the nasal cavity. Computational simulation of a particle-laden flow is performed in the nasal cavity of a healthy patient and a patient with rhinitis. The numerical results of this work open up new possibilities for proposing an alternative user-friendly plan that can essentially improve local drug delivery to the human nasal cavity.

A Breath of Relief: Oxymetazoline and Flunisolide Nasal Spray in the Management of Myasthenia Gravis Ptosis

A Breath of Relief: Oxymetazoline and Flunisolide Nasal Spray in the Management of Myasthenia Gravis Ptosis

A randomized, double-blind study to compare the efficacy and safety of nalbuphine nasal spray and injectable solution in patients after orthopaedic interventions and traumatological procedures.

Our previous 3-period crossover study in healthy volunteers comparing the pharmacokinetics of nalbuphine nasal spray Apain with parenteral nalbuphine solution demonstrated high bioavailability of the nasal spray and close similarity of pharmacokinetic profiles after intranasal and intramuscular administration, especially within 30 min postdose. The aim of the present study was a noninferiority assessment of nalbuphine nasal spray vs. intramuscular injection for pain relief in postoperative patients. Ninety orthopaedic and traumatology patients were enrolled in this double-blind, randomized study of the effectiveness and tolerance of a single 10.5mg dose of nalbuphine nasal spray vs. 10mg intramuscular injection. The summed pain intensity difference (SPID0-6) calculated using visual analogue scale scores was the primary study endpoint. Of 90 subjects enrolled, the per-protocol efficacy population comprised 79 patients; 6 patients in the reference group and 5 patients in the test group were excluded due to remedication. The mean values of study endpoints with 95% confidence interval were as follows in reference and test groups, respectively: SPID0-6= 228.08 (205.73-250.43) vs. 248.73 9 (225.83-271.63), time to pain relief onset =0.28 h (0.25-0.31) vs. 0.27 h (0.25-0.29), duration of analgesia =5.55 h (5.17-5.93) vs. 5.51 h (5.10-5.92), area under the curve = 119.30 (91.17-147.43) vs. 99.81 (74.52-107.10). No statistically significant differences were revealed. Nalbuphine nasal spray Apain has been proven to be a safe, noninvasive alternative to intramuscular nalbuphine to relieve severe postoperative pain. Designed for self-administration and dose-adjusting, the noncontrolled opioid analgesic nalbuphine spray can be used for patient-controlled analgesia in out-of-hospital, field and home settings.

Heparin-mediated PCR interference in SARS-CoV-2 assays and subsequent reversal with heparinase I

Heparin is postulated to block the interaction of SARS-CoV-2 with highly glycosylated proteins which are critical for binding the angiotensin-converting enzyme 2 (ACE2), an essential mechanism for host-cell entry and viral replication. Intranasal heparin is under investigation for use as a SARS-CoV-2 preventative in the IntraNasal Heparin Trial (INHERIT, NCT05204550). Heparin directly interferes with real-time quantitative polymerase chain reaction (RT-qPCR), the gold standard for SARS-CoV-2 detection. This study aimed to investigate the magnitude of heparin interference across various clinical laboratory testing platforms, and the reversal of any interference by degradation of heparin using the heparinase I enzyme in nasopharyngeal swab (NP) samples for SARS-CoV-2 analysis by RT-qPCR. Heparin-mediated PCR interference was evident at heparin concentrations as low as 10 IU/mL across all platforms tested, with the exclusion of the Hologic Panther Aptima SARS-CoV-2 assay. Rates of false negative or invalid results increased with increasing heparin concentrations on all platforms, except the Hologic Panther Aptima and Roche Cobas LIAT. Heparinase I reversed heparin-mediated PCR inhibition across in all samples tested, except those with initial Ct values >35. Our study shows that the use of heparin-containing nasal sprays interferes with the detection of SARS-CoV-2 in NP swab samples by RT-qPCR, a phenomenon that is not well recognised in the literature. Furthermore, this study has also demonstrated that heparin-mediated PCR inhibition can be prevented through heparinase I treatment, demonstrating restoration of clinically significant results with Ct values <35.

Posterior Nasal Nerve Ablation as a Viable Treatment Option for the Primary Symptom of Postnasal Drip.

Postnasal drip (PND) syndrome is a prevalent complaint encountered in otolaryngology practices. PND may be refractory to medical therapy, and surgical treatments are complicated by side effects. While posterior nasal nerve (PNN) ablation has demonstrated efficacy for chronic rhinitis overall, we sought to examine the effect of PNN ablation for patients with PND as their primary complaint. This is a retrospective case series study of 40 chronic rhinitis (CR) patients with a primary complaint of PND. Included patients had to have failed medical therapy such as anti-cholinergic nasal sprays, reflux treatments, and/or nasal steroids. Primary outcome measures included 22 item Sino-Nasal Outcome Test (SNOT-22) PND component and Total Nasal Symptom Score. Secondary outcome measure was subjective improvement, defined as a  > 30% improvement in PND symptoms. Median follow-up was 138 days (interquartile range: 72-193). 72.5% (29/40) of patients reported at least a 30% improvement in PND symptoms. Mean PND SNOT-22 scores were 4.2/5 (SD = 0.8) pre-procedure versus 1.9/5 (SD = 1.3) post-procedure (P = .001). PNN ablation response did not correlate to ipratropium bromide nasal spray response, although younger and non-smoker patients had better response rates. This exploratory study of PNN ablation for the primary symptom of PND demonstrates efficacy as assessed by the PND component of SNOT-22 and subjective improvement. These results can be useful in guiding physician-patient discussions in determining treatment options for medically refractory PND.

Characterization of nasal spray aerosol fields using the extended interferometric particle imaging technique

Nasal-drug-delivery is an effective way to improve therapeutic effect. Droplet diameter and its distribution directly impact the deposition position and bioavailability of the drug in nasal passage. In this paper, the spatial distribution of the droplet size, location and refractive index of spray are explored with extended interferometric particle imaging technique. A generalized expression of the spatial spacing of interference fringes is derived theoretically. The fringe spacing for two counter-propagating beams is the same as that for a single beam along one of the two-beam directions at the sideward scattering region, which is verified by simulation and experiment. The polystyrene microsphere and the nasal spray of physiological saline and oxytocin are tested experimentally. The relative error of microsphere size is less than 0.3 %, the refractive index accuracy of spray can reach 10−4. The method presented herein is promising for many relevant applications, such as fuel spray and nasal spray.

Development of a sustainable procedure for smartphone-based colorimetric determination of benzalkonium chloride in pharmaceutical preparations

A sustainable procedure offering green, simple, and rapid analysis was developed to determine benzalkonium chloride (BKC) in pharmaceutical preparations. The determination using smartphones was based on the ion pair colorimetric reaction with bromothymol blue (BTB), which produces a yellow color. The intensity of the product color, which is proportional to the concentration of BKC, was detected and evaluated using a smartphone camera and an image processing application. The procedure was performed in a microliter and was rapidly detected within 1 min after incubation. This offered high throughput at 28 samples per well plate in duplicate. Linear calibration, which was a plot of BKC concentrations and relative red intensities, was in the range of 2.0–24.0 μg/mL with an R2 of 0.997. The limits of detection (LOD) and quantitation (LOQ) were 1.0 and 3.2 μg/mL, respectively. This work was successful in applying it to pharmaceutical materials, disinfectant products, and pharmaceutical products containing BKC. It was discovered that the concentrations of BKC as an active ingredient in pharmaceutical materials were 82% w/v, whereas those in disinfectant products ranged from 0.4 to 2.1% w/v. In pharmaceutical products, ophthalmic drops and nasal sprays contain BKC as preservatives in the 0.01–0.02, and the 0.02% w/v, respectively. The results obtained by the proposed procedure compared with a reference titration method showed no significant differences at a 95% confidence level with 1.2–3.4% RSDs. This promotes the efficiency of pharmaceutical preparations regarding infection prevention and control by ensuring that available disinfectants contain a sufficient concentration of BKC. Additionally, this improves the efficiency of pharmaceutical preparations for quality control of pharmaceutical products by ensuring that the available preservatives maintain a sufficient concentration throughout the lifespan of the products.

Perspectives in treatment-resistant depression: esketamine and electroconvulsive therapy.

Modern electroconvulsive therapy (ECT) and the approval of nasal esketamine for clinical use have significantly improved the approach to treatment-resistant depression (TRD), which is defined as non-response to at least two different courses of antidepressants with verified adherence to treatment, adequate dosage, and duration of treatment. The goal of this literature review is to present the newest evidence regarding efficacy and safety. Furthermore, we aim to provide an overview of future perspectives in this field of research, for example, regarding structural and molecular effects. Both treatment methods will be critically evaluated for their individual advantages, disadvantages, and response rates. Firstly, we will discuss the well-established method of ECT and its different treatment modalities. Secondly, we will discuss the properties of ketamine, the discovery of its antidepressive effects and the route to clinical approval of the esketamine nasal spray. We will comment on research settings which have evaluated intravenous ketamine against ECT. The decision-making process between esketamine nasal spray or ECT should include the assessment of contraindications, age, severity of disease, presence of psychotic symptoms, patient preference and treatment accessibility. We conclude that both treatment options are highly effective in TRD. If both are indicated, pragmatically esketamine will be chosen before ECT; however, ECT studies in ketamine non-responders are missing.

Nalmefene study: A faster alternative to naloxone

In the first head‐to‐head study of nalmefene nasal spray (OPVEE is the trade name) vs. naloxone to reverse opioid overdose conducted in volunteers, researchers found that nalmefene worked faster than a 4 milligram (mg) dose of naloxone. It worked much faster, in fact, 2.7 mgs of OPVEE reversed respiratory depression within 5 minutes, compared to 20 minutes for 4 mgs of naloxone. The opioid that was given to the volunteers was remifentanil, a synthetic opioid.

Comparative study of nasal cavity drug delivery efficiency with different nozzles in a 3D printed model.

Nasal sprays are widely used in treating nasal and sinus diseases; however, there are very few studies on the drug delivery efficiency of nasal sprays. In this study, the drug delivery efficiency of three different nasal spray devices was evaluated in vitro using a 3D printed cast model of nasal cavity. Three nasal spray devices with different nozzles and angles of administration were used in the 3D model of the nasal cavity and paranasal sinuses. The spraying area (SA), maximal spraying distance (MSD), and spraying distribution scores on the nasal septum and lateral nasal wall were recorded. Different nasal spray devices have their own characteristics, including volume of each spray, SA, and plume angle. The SA of the three nozzles on the nasal septum increased with an increasing angle of administration. When the angle of administration was 50°, each nozzle reached the maximal SA. There was no statistically significant difference in MSD among the three nozzles at the three angles. The total scores for each nozzle using the three different spraying angles were as follows: nozzle A, 40°>30°>50°; nozzle B, 30°>40°>50°; and nozzle C, 30°>40°>50°. The total scores for different nozzles using the same angle were statistically significantly different and the scores for nozzle C were the highest. Nozzle C had the minimum plume angle. None of the three nozzles could effectively delivered drugs into the middle meatus at any angle in this model. The design of the nozzle affects drug delivery efficiency of nasal spray devices. The ideal angle of administration is 50°. The nozzle with smaller plume angle has higher drug delivery efficiency. Current nasal spray devices can easily deliver drugs to most areas of the nasal cavity, such as the turbinate, nasal septum, olfactory fissure, and nasopharynx, but not the middle meatus. These findings are meaningful for nozzle selection and device improvements.

Long-term Safety and Tolerability of Zavegepant 10 mg Nasal Spray in the Acute Treatment of Migraine Among Female Adults (P6-12.001)

Long-term Safety and Tolerability of Zavegepant 10 mg Nasal Spray in the Acute Treatment of Migraine Among Female Adults (P6-12.001)