Clinical trial evaluating apomorphine oromucosal solution in Parkinson's disease patients.

Apomorphine, used to treat OFF episodes in patients with Parkinson's disease (PD), is typically administered via subcutaneous injections. Administration of an oromucosal solution could offer a non-invasive and user-friendly alternative. This two-part clinical study evaluated the safety, tolerability, pharmacokinetics (PK), and dose proportionality of a novel apomorphine hydrochloride oromucosal solution, as well as its relative bioavailability to subcutaneous apomorphine injection and apomorphine sublingual film. In part A of the study, 12 patients with PD received 2 mg oromucosal apomorphine (4% weight/volume) and 2 mg subcutaneous apomorphine in a randomized order, followed by 4 and 8 mg oromucosal apomorphine. In part B of the study, 13 patients with PD received 7 mg oromucosal apomorphine (7% weight/volume) and 30 mg sublingual apomorphine in a randomized order, followed by 14 mg oromucosal apomorphine. Washout between dose administrations in both study parts was at least 2 days. Safety, tolerability, and PK were assessed pre- and post-dose. Both study parts showed that oromucosal apomorphine was generally well-tolerated. Observed side effects were typical for apomorphine administration and included asymptomatic orthostatic hypotension, yawning, fatigue, and somnolence. Oromucosal apomorphine exposure increased with dose, although less than dose proportional. The mean (SD) maximum exposure reached with 14 mg oromucosal apomorphine was 753.0 (298.6) ng*min/mL (area under the plasma concentration-time curve from zero to infinity) and 8.0 (3.3) ng/mL (maximum plasma concentration). This was comparable to exposure reached after 2 mg subcutaneous apomorphine and approximately half of the exposure observed with 30 mg sublingual apomorphine. In summary, clinically relevant plasma concentrations could be reached in PD patients without tolerability issues.

[ROUTES OF MEDICAL CANNABIS ADMINISTRATION- IS SMOKING THE PREFERRED ROUTE?]

INTRODUCTION: The number of medical cannabis licenses in Israel is increasing persistently (over 120,000 approved licenses in October 2022), reaching about 1.5% of adult population. Medical cannabis products are available in two main forms: inflorescence (administered by smoking or evaporation) and cannabis oil (administered sub-lingually). Data from the Israel ministry of health, regarding the split between these forms, show a major preference for inflorescence products over cannabis oils. This preference is increasing over time. This article reviews the main differences between the administration of these forms and their effects on the quality of treatment. It's conclusion is that for the most common cases of cannabis treatment, sublingual oils should be preferred and that the medical community has an important role in driving this change.

Novel fast dissolving freeze dried sublingual baicalin tablets for enhanced hepatoprotective effect: in-vitro characterization, cell viability, and in-vivo evaluation.

Baicalin (BG), a natural product, has been used in the prevention and treatment of drug-induced liver injury (DILI); however, its poor solubility and extensive liver metabolism limit its pharmacological use. The aim of the present study was the formulation of fast-dissolving freeze-dried sublingual tablets (FFSTs) to increase BG dissolution, avoid first-pass metabolism, and overcome swallowing difficulties. FFSTs were prepared following a 23 factorial design. The effect of three independent variables namely matrix former, Maltodextrin, concentration (4%, and 6%), binder concentration (2%, and 3%), and binder type (Methocel E5, and Methocel E15) on the FFSTs' in-vitro disintegration time and percentage dissolution was studied along with other tablet characteristics. Differential scanning calorimetry, scanning electron microscopy, in-vitro HepG2 cell viability assay, and in-vivo characterization were also performed. F8 (6% Maltodextrin, 2% Mannitol, 2% Methocel E5), with desirability of 0.852, has been furtherly enhanced using 1%PEG (F10). F10 has achieved an in-vitro disintegration time of 41 secs, and 60.83% in-vitro dissolution after 2 min. Cell viability assay, in-vivo study in rats, and histopathological studies confirmed that pretreatment with F10 has achieved a significant hepatoprotective effect against acetaminophen-induced hepatotoxicity. The outcome of this study demonstrated that FFSTs may present a patient-friendly dosage form against DILI.

SQ sublingual immunotherapy tablets for children with allergic rhinitis: A review of phase three trials.

AIM: To provide paediatricians with a summary of efficacy and safety of SQ sublingual immunotherapy (SLIT) tablets from phase three, randomised, double-blind, placebo-controlled trials in children and adolescents with allergic rhinitis or rhinoconjunctivitis, with and without asthma. METHODS: PubMed searches were conducted and unpublished data were included if necessary. RESULTS: Of the 93 publications, 12 were identified reporting 10 trials. One trial was excluded as paediatric-specific efficacy data were unavailable. The nine eligible trials evaluated grass, house dust mite, ragweed and tree SLIT tablets. Consistent reductions in allergic rhinitis or rhinoconjunctivitis symptoms and medication use were observed with SQ SLIT tablets versus placebo. In a five-year trial, sustained reduction of allergic rhinoconjunctivitis symptoms, asthma symptoms and medication use were observed with SQ grass SLIT tablet versus placebo. The number-needed-to-treat to prevent asthma symptoms and medication use in one additional child during follow-up was lowest in younger children. SQ SLIT tablets were generally well tolerated across trials. CONCLUSION: Evidence supports use of SQ SLIT tablets in children and adolescents with allergic rhinitis or rhinoconjunctivitis, with and without asthma. Long-term data demonstrate disease-modifying effects of SQ grass SLIT tablet and suggest the clinical relevance of initiating allergy immunotherapy earlier in the disease course.

The Devil's in the Depot Details: Case of Iatrogenic Opioid Intoxication After Buprenorphine Injection Requiring Surgical Excision.

ABSTRACT: Monthly long-acting injectable buprenorphine (LAI-BUP) is a treatment option for moderate to severe opioid use disorder. Safe administration of LAI-BUP requires preexisting opioid tolerance to prevent sedation and respiratory depression. In the event of adverse medication effects including oversedation, LAI-BUP can be surgically excised up to 14 days after administration ( https://www.sublocadehcp.com/dosing-administration ). However, the manufacturer does not provide guidance on the proper procedure for excision, and no case reports have been published documenting this procedure. We report a case of a man with methamphetamine use disorder and multiple unintentional fentanyl overdoses who inadvertently received LAI-BUP for overdose protection. This resulted in significant sedation for days, ultimately necessitating excision 5 days after administration. His sedation improved moderately at 24 hours after excision and significantly by 36 hours after excision. Providers seeking to use LAI-BUP to prevent overdose among those with unintentional opioid exposure must ensure sublingual buprenorphine tolerance before injection to avoid iatrogenic harm. Although manufacturer instructions mention that LAI-BUP can be excised under local anesthesia within 14 days of insertion, ideal excision is best performed in a setting with surgical instruments and cautery-such as the operating room-as the depot can adhere strongly to the surrounding subcutaneous tissue.

Systemic delivery of proteins using novel peptides via the sublingual route.

Therapeutic proteins often require needle-based injections, which compromise medication adherence especially for those with chronic diseases. Sublingual administration provides a simple and non-invasive alternative. Herein, two novel peptides (lipid-conjugated protamine and a protamine dimer) were synthesized to enable sublingual delivery of proteins through simple physical mixing with the payloads. It was found that the novel peptides promoted intracellular delivery of proteins via increased pore formation on the cell surface. Results from in vitro models of cell spheroids and human sublingual tissue substitute indicated that the novel peptides enhanced protein penetration through multiple cell layers compared to protamine. The novel peptides were mixed with insulin or semaglutide and sublingually delivered to mice for blood glucose (BG) control. The effects of these sublingual formulations were comparable to the subcutaneous preparations and superior to protamine. In addition to peptide drugs, the novel peptides were shown to enable sublingual absorption of larger proteins with molecular weights from 22 to 150 kDa in mice, including human recombinant growth hormone (rhGH), bovine serum albumin (BSA) and Immunoglobulin G (IgG). The novel peptides given sublingually did not induce any measurable toxicities in mice.

Safety and Effectiveness of Bypassing Oral Immunotherapy Buildup With an Initial Phase of Sublingual Immunotherapy for Higher-Risk Food Allergy.

BACKGROUND: Because of its favorable safety, sublingual immunotherapy (SLIT) for food allergy has been proposed as an alternative treatment for those in whom oral immunotherapy (OIT) is of higher risk-older children, adolescents, adults, and those with a history of severe reactions. Although safe, SLIT has been shown to be less effective than OIT. OBJECTIVE: To describe the safety of multifood SLIT in pediatric patients aged 4 to 18 years and the effectiveness of bypassing OIT buildup with an initial phase of SLIT. METHODS: Patients aged 4 to 18 years were offered (multi)food SLIT. Patients built up to 2 mg protein SLIT maintenance over the course of 3 to 5 visits under nurse supervision. After 1 to 2 years of daily SLIT maintenance, patients were offered a low-dose oral food challenge (OFC) (cumulative dose, 300 mg protein) with the goal of bypassing OIT buildup. RESULTS: Between summer 2020 and winter 2023, 188 patients were enrolled in SLIT (median age, 11 years). Four patients (2.10%) received epinephrine during buildup and went to the emergency department, but none experienced grade 4 (severe) reaction. A subset of 20 patients had 50 low-dose OFCs to 300 mg protein and 35 (70%) OFCs were successful, thereby bypassing OIT buildup. CONCLUSIONS: In combination with very favorable safety of SLIT, with no life-threatening reactions and few reactions requiring epinephrine, we propose that an initial phase of SLIT to bypass supervised OIT buildup be considered for children in whom OIT is considered to be of higher risk.

Desensitization and remission after peanut sublingual immunotherapy in 1- to 4-year-old peanut-allergic children: A randomized, placebo-controlled trial.

BACKGROUND: Prior studies of peanut sublingual immunotherapy (SLIT) have suggested a potential advantage with younger age at treatment initiation. OBJECTIVE: We studied the safety and efficacy of SLIT for peanut allergy in 1- to 4-year-old children. METHODS: Peanut-allergic 1- to 4-year-old children were randomized to receive 4 mg peanut SLIT versus placebo. Desensitization was assessed by double-blind, placebo-controlled food challenge (DBPCFC) after 36 months of treatment. Participants desensitized to at least 443 mg peanut protein discontinued therapy for 3 months and then underwent DBPCFC to assess for remission. Biomarkers were measured at baseline and longitudinally during treatment. RESULTS: Fifty participants (25 peanut SLIT, 25 placebo) with a median age of 2.4 years were enrolled across 2 sites. The primary end point of desensitization was met with actively treated versus placebo participants having a significantly greater median cumulative tolerated dose (4443 mg vs 143 mg), higher likelihood of passing the month 36 DBPCFC (60% vs 0), and higher likelihood of demonstrating remission (48% vs 0). The highest rate of desensitization and remission was seen in 1- to 2-year-olds, followed by 2- to 3-year-olds and 3- to 4-year-olds. Longitudinal changes in peanut skin prick testing, peanut-specific IgG4, and peanut-specific IgG4/IgE ratio were seen in peanut SLIT but not placebo participants. Oropharyngeal itching was more commonly reported by peanut SLIT than placebo participants. Skin, gastrointestinal, upper respiratory, lower respiratory, and multisystem adverse events were similar between treatment groups. CONCLUSION: Peanut SLIT safely induces desensitization and remission in 1- to 4-year-old children, with improved outcomes seen with younger age at initiation.

Sublingual immunotherapy for cedar pollinosis possibly triggers eosinophilic esophagitis.

Sublingual immunotherapy (SLIT) is an effective and popular treatment for cedar pollinosis. Although SLIT can cause allergic side effects, eosinophilic esophagitis (EoE) is a lesser-known side effect of SLIT. A 26-year-old male with cedar pollinosis, wheat-dependent exercise-induced anaphylaxis, and food allergies to bananas and avocados presented with persistent throat itching, difficulty swallowing, heartburn, and anterior chest pain 8 days after starting SLIT for cedar pollinosis. Laboratory examination showed remarkably elevated eosinophils, and esophagogastroduodenoscopy revealed linear furrows in the entire esophagus. Histological examination of an esophageal biopsy specimen revealed high eosinophil levels. The patient was strongly suspected with EoE triggered by SLIT. The patient was advised to switch from the swallow to the spit method for SLIT, and the symptoms associated with SLIT-triggered EoE were reduced after switching to the spit method. This case highlights the importance of recognizing SLIT-triggered EoE as a potential side effect of SLIT for cedar pollinosis, especially with the increasing use of SLIT in clinical practice. EoE can occur within a month after initiating SLIT in patients with multiple allergic conditions, as observed in our case. Furthermore, the spit method should be recommended for patients who experience SLIT-triggered EoE before discontinuing SLIT.

Tolerability of sublingual versus vestibular allergy immunotherapy tablet administration: A randomized pilot study.

BACKGROUND: Local application site reactions are common with sublingual allergy immunotherapy (AIT)-tablets for the treatment of allergic rhinitis/conjunctivitis (AR/C) and occasionally lead to treatment discontinuation. Because of the lower mast cell density in the vestibular mucosa than the sublingual area, vestibular AIT-tablet administration may result in fewer adverse events (AEs). This pilot study evaluated the tolerability of the vestibular administration route of AIT-tablets compared with the sublingual route in adult subjects with AR/C. METHODS: Adults (n = 164) aged 18-65 years with AR/C treated with daily birch pollen, grass pollen, ragweed pollen or house dust mite AIT in tablet form were randomized 1:1 to vestibular or sublingual administration for 28 days, followed by 28 days of sublingual administration only. The primary endpoint was the severity (mild, moderate, severe) of local treatment-related adverse events (TRAEs) during the first 28 days of treatment. RESULTS: During the first 28 days, the percentage of subjects in the vestibular and sublingual groups reporting mild TRAEs were 55.6% versus 50.6%, respectively; moderate TRAEs were 27.2% versus 30.1%; and severe TRAEs were 12.3% versus 6.0% (p = .16). In the vestibular group, 95.1% of the subjects experienced at least one TRAE during the first period versus 81.9% in the sublingual group (p = .01) and discontinuation rates due to AEs were higher (12.3% vs. 3.6%). CONCLUSION: The frequencies of subjects experiencing severe TRAEs, at least one TRAE, and discontinuations due to AEs at the initiation of AIT-tablets were numerically higher with vestibular administration than sublingual administration. Sublingual administration should remain the standard of care for subjects treated with AIT-tablets for AR/C.

Sublingual Administration of Teucrium Polium-Loaded Nanofibers with Ultra-Fast Release in the Treatment of Diabetes Mellitus: In Vitro and In Vivo Evaluation.

In this study, Teucrium polium (TP) methanolic extract, which has antidiabetic activity and protects the ß-cells of the pancreas, was loaded in polyethylene oxide/sodium alginate nanofibers by electrospinning and administered sublingually to evaluate their effectiveness in type-2 diabetes mellitus (T2DM) by cell culture and in vivo studies. The gene expressions of insulin, glucokinase, GLUT-1, and GLUT-2 improved in TP-loaded nanofibers (TPF) on human beta cells 1.1B4 and rat beta cells BRIN-BD11. Fast-dissolving (<120 s) sublingual TPF exhibited better sustainable anti-diabetic activity than the suspension form, even in the twenty times lower dosage in streptozotocin/nicotinamide-induced T2DM rats. The levels of GLP-1, GLUT-2, SGLT-2, PPAR-γ, insulin, and tumor necrosis factor-alpha were improved. TP and TPF treatments ameliorated morphological changes in the liver, pancreas, and kidney. The fiber diameter increased, tensile strength decreased, and the working temperature range enlarged by loading TP in fibers. Thus, TPF has proven to be a novel supportive treatment approach for T2DM with the features of being non-toxic, easy to use, and effective.

[Efectividad de la suspensión bacteriana sublingual en la prevención de infecciones de vías aéreas de repetición en pediatría].

Background: Upper respiratory tract infections (URIs) are very common in the pediatric population. Most of these infections are mild, but due to their chronicity they affect quality of life (QoL), in addition to high costs for medical care. The use of bacterial extracts (BE) that stimulate general immunity can reduce its frequency and improve the QoL of the patient. Objective: Evaluate the effectiveness of a BE in the prevention of ARVI in children from 1 to 6 years of age. Methods: Children between the ages of 1 and 6 years, with a diagnosis of RAVI, were randomized into 3 different groups, with medical follow-up at 6 and 12 weeks after the start. The EB was administered with different doses to each group. An ANOVA test with a Tukey post hoc is used for multiple comparisons (maximum type I error of 0.05). Results: 33 children (12 girls) with a mean age of 3.11 years were included. The average frequency of RAVI prior to treatment was 2.2 events/month and 0.9 and 0.4 events/month at 6 and 12 weeks, respectively. The IVARS were reduced by 76.9% at 3 months of treatment. (Graph). No adverse effects were reported. Conclusions: BE is safe and effective in reducing the frequency of RAVI in children, in agreement with the literature. There is not enough published scientific evidence, but the BE seems to have an application in the prevention and treatment of RAVI. Sublingual administration is comfortable in this age group.

Antecedentes: Las infecciones de vías aéreas superiores (IVASR) son muy frecuentes en la población pediátrica. La mayoría de estas infecciones son leves, pero por la cronicidad afectan la calidad de vida (CdV), además de elevados costos por la atención médica. El uso de extractos bacterianos (EB) que estimulen la inmunidad general pueden reducir su frecuencia y mejorar la CdV del paciente. Objetivo: Evaluar la efectividad de un EB en la prevención de IVASR en niños de 1 a 6 años. Métodos: Se aleatorizaron niños entre 1 y 6 años, con diagnóstico IVASR en 3 grupos distintos, seguimiento médico a las 6 y 12 semanas tras el inicio. El EB se administró con dosis distintas a cada grupo. Se utiliza una prueba de ANOVA con un post hoc Tukey para comparaciones múltiples (error tipo I máximo de 0.05). Resultados: Se incluyeron 33 niños (12 niñas) con una media de edad de 3.11 años. La frecuencia de IVASR previo al tratamiento en promedio fue de 2.2 eventos/mes y de 0.9 y de 0.4 eventos/mes a las 6 y 12 semanas respectivamente. La IVARS se redujeron un 76.9% a los 3 meses de tratamiento. (Gráfica). No se reportaron efectos adversos. Conclusiones: El EB es seguro y efectivo en disminuir la frecuencia de IVASR en niños en concordancia con la literatura. No hay suficiente evidencia científica publicada pero el EB parece tener aplicación en la prevención y tratamiento de las IVASR. La administración sublingual es cómoda en este grupo etario.

Low-dose Initiation of Buprenorphine in Hospitalized Patients on Full Agonist Opioid Therapy: A Retrospective Observational Study.

OBJECTIVE: Buprenorphine can be challenging to initiate in hospitalized patients with opioid dependence because of difficulty tolerating an opioid-free period for buprenorphine induction. The objective of this study was to evaluate efficacy and safety of low-dose initiation of buprenorphine in hospitalized patients receiving full agonist opioids. METHODS: This is a retrospective observational study between January 1, 2019, and December 31, 2020, at an academic tertiary care center and affiliated community hospital. Participants included adult patients at least 18 years old receiving scheduled full agonist opioids who were given sublingual buprenorphine 0.5 mg or less with the intent of increasing to at least 4 mg daily. The primary endpoint was the proportion of patients reaching a target dose of at least 4 mg total per day. The secondary endpoints included the incidence of precipitated opioid withdrawal based on documentation of symptoms and change in morphine milligram equivalents before and after low-dose buprenorphine initiation. RESULTS: A total of 76 low-dose initiation attempts were performed in 71 predominantly male (68%) patients (some patients had multiple attempts). Most patients received low-dose initiation because of history of opioid use disorder (83%). Low-dose initiation was completed in 54 of 71 patients (76%) after 76 attempts. Precipitated withdrawal was identified in 2 patients (2.8%). Median morphine milligram equivalents excluding buprenorphine 24 hours before low-dose initiation was 1000 mg (interquartile range, 303.5-1720.5 mg) compared with 37.5 mg (interquartile range, 0-254 mg) after reaching target dose ( P < 0.001). CONCLUSIONS: Buprenorphine was safely initiated using low-dose initiation in hospitalized patients. This was associated with significant reduction in full agonist opioids.

Collaborative rp-hplc method development for modafinil and scopolamine hydrobromide in sublingual tablets: involving key industry players

Objective: This research aims to develop and validate a collaborative RP-HPLC method, with input from key industry players, for the simultaneous determination of modafinil and scopolamine hydrobromide in compound sublingual tablets. The focus is on ensuring the safety and efficacy of these substances for enhancing the physical and cognitive fitness of athletes and players. Method: Utilizing a C18 chromatographic column (200mm×4.6mm, 5μm), the method employs a mobile phase of acetonitrile-water (25:75) with 0.02mol/L ammonium acetate and 0.02% triethylamine, pH adjusted to 6.0. The flow rate was set at 1 mL/min, detection at 225 nm wavelength, and an injection volume of 20 μL.Results: Scopolamine hydrobromide showed a linear range of 1-50 μg/mL, with a standard curve equation of A=0.2187C+0.0708 (R²=0.9993), and modafinil exhibited a range of 10-500 μg/mL, with A=0.6702C-1.6855 (R²=0.9993). Both substances demonstrated average recoveries of over 99%, within acceptable variance limits, signifying reliable quantification for fitness-related applications. Conclusion: The developed method is sensitive, precise, accurate, and reproducible, conforming to the standards of the Chinese Pharmacopoeia (2020 edition). It is particularly valuable for monitoring the quality of substances used by athletes and players to ensure their safe application in enhancing fitness and performance. The method benefits significantly from the collaboration with industry experts, addressing the specific needs of fitness and sports professionals (AU)

Sublingual/Buccal buprenorphine and dental problems: a pharmacovigilance study.

BACKGROUND: The association between dental problems and sublingual/buccal buprenorphine is unclear. We conducted an analysis of dental adverse drug reactions reported with sublingual/buccal buprenorphine in VigiBase®, the pharmacovigilance database of the World Health Organization. RESEARCH DESIGN AND METHODS: We performed disproportionality analyses to compare the reporting rates of dental problems with sublingual/buccal buprenorphine, compared to other buprenorphine formulations and methadone. Significant signals were considered if the lower boundary of the 95% confidence interval of the Reporting Odds Ratio (ROR) was > 1; cases were ≥ 3 and p-value <0.05. We conducted sensitivity analyses by calculating the ROR according to the reporter's qualification and the reporting continent (United States of America and Europe). RESULTS: We included 30,769 reports with all buprenorphine forms. We found 20 cases of dental problems with sublingual/buccal buprenorphine. Sublingual/buccal buprenorphine was associated with an overreporting of dental problems compared to other buprenorphine formulations (ROR = 15.10; 95% CI [7.50-30.39]; p < 0.005) and compared to methadone (ROR = 6.02; 95% CI [3.21-11.30]; p < 0.005). Overreporting of dental problems was consistent in sensitivity analyses, except in Europe compared with other buprenorphine formulations and with methadone. CONCLUSIONS: Sublingual/buccal buprenorphine might increase the risk of reporting dental problems. However, these results do not modify the benefits of sublingual/buccal buprenorphine in the treatment of opioid use disorders.

Use of Video Directly Observed Therapy and Characteristics Associated With Use Among Patients Treated With Buprenorphine in an Office-based Setting.

OBJECTIVES: Video directly observed therapy (video DOT) is a tool for confirming buprenorphine adherence that could complement the use of urine toxicology; research is needed to characterize the patients who are receptive and able to use this technology. We aimed to describe video DOT utilization and assess participant characteristics associated with use. METHODS: We performed a secondary analysis of data from a pilot randomized controlled trial of adults who recently initiated sublingual buprenorphine in office-based programs, restricting to intervention arm participants, which consisted of 12 weeks of video DOT via a mobile health technology platform. Participants were instructed to record at least 1 daily video of buprenorphine self-administration. Poisson regression models with robust standard errors were used to measure associations between participant characteristics and frequency of submitted videos. RESULTS: The sample included 39 participants. Of 3276 possible videos, 1002 (31%) were submitted. Age ≥40 years (relative risk [RR], 2.54 [95% confidence interval {CI}, 1.31-4.91]) and once-daily buprenorphine dosing (RR, 3.10 [95% CI, 1.76-5.48]) were positively associated with video submissions. Non-White race (RR, 0.43 [95% CI, 0.19-0.97]), less than high school education (RR, 0.27 [95% CI, 0.10-0.74]), history of previous buprenorphine treatment (RR, 0.50 [95% CI, 0.25-0.97]), and ≥3 previous treatment attempts (RR, 0.16 [95% CI, 0.07-0.37]) were negatively associated. CONCLUSIONS: Video DOT utilization resulted in about a third of expected videos, although there were differences in use according to age, race, buprenorphine treatment factors, and educational status. Such differences underscore that mobile-health interventions such as video DOT may not be equally used by all patients.Trial Registration : ClinicalTrails.gov , NCT03779997 , registered on December 19, 2018.

Dental adverse effects of sublingual buprenorphine and naloxone.

Overview of: Etminan M, Rezaeianzadeh R, Kezouh A, et al. Association between sublingual buprenorphine-naloxone exposure and dental disease. JAMA. 2022;328:2269-71.

Successful Premedication With Sublingual Midazolam Using a Suction Toothbrush.

Premedication is often used to reduce the stress associated with anesthesia-related procedures. However, in some cases, patients may not cooperate with medication delivery because of significant fear and anxiety. We report a case of an uncooperative patient with severe intellectual disabilities who was successfully premedicated with the unique technique of sublingual midazolam administration using a suction toothbrush. The 38-year-old male patient was planned to receive dental treatment under deep intravenous sedation (IVS), but he refused both intravenous cannulation and mask induction. Preanesthetic medication delivery using other routes was attempted but not accepted. As the patient tolerated toothbrushing, we used repeated practice with sublingual water administration through the toothbrush's suction hole to gradually desensitize the patient. Using that same method, sublingual midazolam was administered as a successful premedication to allow placement of a face mask for inhalational induction without distress and completion of the dental treatment under IVS. For patients who refuse other premedication routes, sublingual administration during toothbrushing with a suction toothbrush may provide a successful alternative.

Efficacy of reconstituted intravenous fentanyl to sublingual solution versus oral morphine syrup for breakthrough pain among patients with chronic gynecologic cancer pain: A randomized, double-blind, placebo-controlled trial.

Rapid-acting fentanyl formulations are superior to oral morphine (OM) syrup in controlling breakthrough pain among patients with cancer, but they are expensive and unavailable in many countries. OBJECTIVE: To evaluate the efficacy of reconstituted intravenous fentanyl to sublingual solution (IFS) in relieving breakthrough pain as compared with OM. METHODS: In this randomized, double-blind, double-dummy, placebo-controlled trial, patients with gynecologic cancer aged ≥18 years experiencing chronic cancer pain with breakthrough pain were enrolled. Patients were randomly allocated (1:1) to receive either 50 µg IFS or 5 mg OM. Pain intensity level was assessed at 5, 15, 30, 45, 60, and 120 min after treatment. The primary outcome was the reduction in pain intensity at 15 min in the intention-to-treat population (ClinicalTrials.gov, NCT05037539). RESULTS: Between June 15, 2021 and December 30, 2021, 40 participants were equally and randomly assigned to receive IFS or OM. The primary outcome was significantly higher in the IFS group (4.25 vs. 1.05, p < 0.0001). The secondary outcomes also showed higher reduction in pain intensity at 5 min in the IFS group. Subsequent breakthrough pain did not differ between the two groups. However, the reduction in pain was lower in the IFS group at 45, 60, and 120 min, where pain was classified as mild. No severe adverse effects were observed in both groups. Burning sensation without noticeable lesion was found in 20% of the IFS group. CONCLUSION: IFS can reduce early breakthrough pain. IFS may be considered for breakthrough pain when rapid-acting fentanyl formulations are unavailable.