Neostigmine 2.5mg/1ml / Glycopyrronium bromide 500micrograms/1ml solution for injection ampoules

BACKGROUND: Hyperhidrosis (HH), characterized by excessive sweating, poses a significant challenge to patients' quality of life. This meta-analysis evaluates the safety and efficacy of topical glycopyrronium bromide (GBP) in treating primary hyperhidrosis, a chronic condition affecting various body regions. Despite its prevalence, primary axillary hyperhidrosis is often undertreated due to a lack of awareness and social stigma. METHODS: Following PRISMA guidelines, we conducted a systematic review and meta-analysis of randomized controlled trials comparing GBP to a placebo in primary hyperhidrosis patients. Eligibility criteria included outcomes related to perspiration suppression and symptom improvement. RESULTS: Four RCTs involving 1401 patients were included. GBP significantly increased Hyperhidrosis Disease Severity Scale (HDSS) responders (RR = 2.33, 95% CI [1.99 to 2.74], p < 0.00001) and Axillary Sweating Daily Diary (ASDD/ASDD-C) responders (MD = 3.07, 95% CI [2.32 to 4.06], p < 0.002) without significantly causing adverse events. Dermatology life quality index was also significantly improved in the GBP group (MD = -2.32, 95% CI [-3.09, -1.55], P < 0.00001). CONCLUSION: GBP demonstrated effectiveness in reducing sweat production while improving HDSS and DLQI scores. Adverse events included dry mouth and anticholinergic effects. Dry eye and local skin reactions were not significant, which makes GBP promising in managing primary hyperhidrosis, offering improvements in symptoms and quality of life. While adverse events should be considered, further research with larger sample sizes and long-term follow-up is warranted for comprehensive clinical integration.

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BACKGROUND: In patients with asthma uncontrolled by a medium or high-strength (MS/HS) inhaled corticosteroid (ICS) plus long-acting β2-agonist (LABA), according to Global Initiative for Asthma (GINA) guidelines, a maintenance therapy option is the addition of a long-acting muscarinic antagonist (LAMA) via single-inhaler triple therapy (SITT). Evidence has previously been published on the cost-effectiveness of a SITT extra fine formulation of beclomethasone, formoterol and glycopyrronium bromide (BDP/FOR/GLY) vs. dual ICS/LABA combination, using data from two 52-week clinical trials (TRIMARAN and TRIGGER). However, there is limited evidence on the comparative cost-effectiveness of SITTs. The current analysis evaluated the cost-effectiveness of BDP/FOR/GLY versus other SITTs, in the UK setting. METHODS: Markov cohort state-transition model was developed to investigate the cost-effectiveness of BDP/FOR/GLY Medium Strength (MS) vs. fluticasone, umeclidinium, and vilanterol (FF/UMEC/VI) MS and, BDP/FOR/GLY High Strength vs. FF/UMEC/VI HS and vs. indacaterol acetate, glycopyrronium bromide, and mometasone (IND/GLY/MF) HS. A network meta-analysis was performed to estimate comparative efficacy of BDP/FOR/GLY against other SITTs. The model analyzed cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER), net monetary benefit (NMB), and was developed from the perspective of England National Health Service (NHS) and Prescribed Specialized Services expenditure (2022 costs). Uncertainty of the inputs was estimated using one-way and probabilistic sensitivity analyses. RESULTS: BDP/FOR/GLY MS was projected to be a dominant treatment alternative against FF/UMEC/VI MS (£5,121 less costly, gained 0.065 additional QALYs). Similarly, BDP/FOR/GLY HS was a dominant treatment alternative against FF/UMEC/VI HS (£143, 0.003 additional QALYs) and IND/GLY/MF HS (£692 less costly, gained 0.023 additional QALYs). BDP/FOR/GLY MS and HS had 77.1%, 51.3%, and 61.2% likelihoods to be cost-effective vs. FF/UMEC/VI MS, FF/UMEC/VI HS, and IND/GLY/MF HS at the defined willingness-to-pay (WTP) threshold of £20,000 per QALY gained, respectively. CONCLUSIONS: BDP/FOR/GLY MS and HS were a dominant treatment alternative compared with FF/UMEC/VI, both MS and HS, and IND/GLY/MF HS in patients with asthma uncontrolled by ICS/LABA.

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Background: the Global Initiative for Chronic Obstructive Lung Disease (COPD) recommends triple therapy as an initial treatment for patients of "group E" (eosinophil count ≥ cells/μL) or as maintenance therapy for patients with frequent exacerbations. Triple therapy combines three types of inhaled medications that help improve lung function, manage symptoms and prevent exacerbations. The use of a single inhaler helps to increase patients' adherence to therapy. Aim: to evaluate the efficacy of the triple combination drug — budesonide/glycopyrronium bromide/formoterol (BUD/GLI/FOR) – and the patients' adherence to the ongoing inhalation therapy of COPD in real clinical practice. Materials and Methods: 30 patients with severe COPD (mean age 65.55±5.98 years) receiving basic therapy in accordance with clinical recommendations during remission were examined. After the initial examination, patients were recommended therapy with a combination of BUD/GLI/FOR 160/7.2/5 μg 2 inhalations twice a day. Patients received the prescribed therapy for 3 months, after which the assessments of therapy adherence and satisfaction with it, the changes concerning the severity of dyspnea (mMRC scale), COPD symptoms (CAT-test), spirometry exams were conducted. Results: after 3 months of therapy with BUD/GLI/FOR, none of the patients had an exacerbation of COPD. During treatment, there was a tendency to decrease the disease severity. No significant changes in spirometry have been established. In 83,3% of cases, patients performed inhalation without errors while reproducing the correct technique. All patients were satisfied with the therapy and were ready to continue treatment. Conclusion: the results obtained serve as the basis for further treatment of patients with COPD with the drug used in real clinical practice and are encouraging in achieving the clinical and functional efficacy announced in randomized clinical trials. KEYWORDS: COPD, triple combination, phospholipids, aerosphere, adherence, inhaled glucocorticosteroid, dual bronchodilator therapy. FOR CITATION: Titova O.N., Kuzubova O.A., Sklyarova D.B. Triple combination drug — budesonide/glycopyrronium bromide/formoterol in patients with chronic obstructive pulmonary disease in real clinical practice (the first domestic experience). Russian Medical Inquiry. 2024;8(8):459–463 (in Russ.). DOI: 10.32364/2587-6821-2024-8-8-3.

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agonists (ICS/LABA) represents a viable add-on therapeutic strategy. Historically, this approach required the use of separate inhalers; however, the recent advent of "single-inhaler triple therapy" (SITT) provided a valuable alternative. One such formulation is the extrafine combination of beclomethasone dipropionate (BDP), fluticasone furoate (FF), and glycopyrronium bromide (GB), which is delivered via a single pressurized metered-dose inhaler (pMDI). Clinical trials, including the TRIMARAN and TRIGGER studies, alongside subsequent post-hoc analyses, have elucidated the benefits of this SITT at both 87/5/9 μg and 172/5/9 μg dosing regimens administered daily. Findings indicated a significant improvement in respiratory function and a reduction in the frequency of exacerbations among patients with uncontrolled asthma. The BDP/FF/GB SITT confirmed efficacy and safety across various ethnic groups (including Caucasian, Japanese, and Chinese populations) and across different age cohorts (adults and adolescents), although it still remains unapproved for individuals under 18 years of age. The use of a single pMDI facilitates the deposition of extra- fine particles from all three active ingredients in the small airways enhancing therapeutic effectiveness. Moreover, the consolidation of medications into one device may improve patients' adherence by mitigating the risks associated with device mismanagement and ensuring optimal drug delivery. The cost-effectiveness analysis of the BDP/FF/GB SITT suggests favorable outcomes compared to traditional ICS/LABA and ICS/LABA plus tiotropium combinations. Additional data will be forthcoming from the ongoing real-life TRIMAXIMIZE observational study.

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BACKGROUND: Primary axillary hyperhidrosis (PAHH) strongly affects the patient's quality of life. To date, topical treatment options are limited. One percent glycopyrronium bromide (GPB) showed promising efficacy and safety in a pivotal 4-week Phase 3a study. OBJECTIVES: To assess efficacy and safety of topical 1% GPB cream in patients with severe PAHH in a long-term study of 72 weeks versus baseline. METHODS: This was a long-term, open-label, Phase 3b trial for 72 weeks including 518 patients with severe PAHH. Patients were treated with 1% GPB cream once daily for 4 weeks, followed by a flexible dosing scheme (min. twice per week, max. once daily). Primary endpoint was the absolute change in sweat production from baseline to week 12. Further study endpoints included assessment of the severity of PAHH and the impact on quality of life. RESULTS: Total median sweat production decreased by 119.30 mg (-65.6%, both median) until week 12. Absolute change in sweat production from baseline to week 12 in logarithmic values was statistically significant (p < 0.0001). Patients' quality of life was improved at all study time points compared to baseline, as assessed by Hyperhidrosis Quality of Life Index and Dermatology Life Quality Index (p < 0.0001). Treatment was safe and locally well-tolerated with only few mild to moderate adverse drug reactions (ADRs). Dry mouth and application site erythema were the most common reported ADRs. CONCLUSIONS: Treatment with 1% GPB cream over 72 weeks significantly reduces sweat production and improves quality of life in patients with severe PAHH. One percent GPB cream is well-tolerated and provides an effective treatment option for long-term use in patients with severe PAHH.

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Use of propellants with high global warming potential (such as HFA-134a) for pressurised metered-dose inhalers (pMDIs) is being phased down. Switching to dry-powder inhalers may not be clinically feasible for all patients; an alternative is reformulation using propellants with low global warming potential. The combination of beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB) is available for asthma or chronic obstructive pulmonary disease via pMDI using HFA-134a as propellant. This is being reformulated using the low global warming potential propellant HFA-152a. This manuscript reports three studies comparing BDP/FF/GB pharmacokinetics delivered via pMDI using HFA-152a vs HFA-134a. The studies were four-way crossover, single-dose, randomised, double-blind, in healthy volunteers. In Studies 1 and 2, subjects inhaled four puffs of BDP/FF/GB (Study 1: 100/6/12.5 μg [medium-strength BDP]; Study 2: 200/6/12.5 μg [high-strength]), ingesting activated charcoal in two of the periods (once per propellant). In Study 3, subjects inhaled medium- and high-strength BDP/FF/GB using a spacer. All three studies compared HFA-152a vs HFA-134a in terms of lung availability and total systemic exposure of beclometasone-17-monopropionate (B17MP; active metabolite of BDP), BDP, formoterol and GB. Bioequivalence was concluded if the 90% confidence intervals (CIs) of the ratios between formulations of the geometric mean maximum plasma concentration (Cmax) and area under the plasma concentration–time curve between time zero and the last quantifiable timepoint (AUC0–t) for the analytes were between 80–125%. In Studies 1 and 2, systemic exposure bioequivalence (i.e., comparisons without charcoal block) was demonstrated, except for GB Cmax in Study 2 (upper 90% CI 125.11%). For lung availability (i.e., comparisons with charcoal block), B17MP and formoterol demonstrated bioequivalence in both studies, as did BDP in Study 2; in Study 1, BDP upper CIs were 126.96% for Cmax and 127.34% for AUC0–t). In Study 1, GB AUC0–t lower CI was 74.54%; in Study 2 upper limits were 135.64% for Cmax and 129.12% for AUC0–t. In Study 3, the bioequivalence criteria were met for BDP, B17MP and formoterol with both BDP/FF/GB strengths, and were met for GB AUC0–t, although not for Cmax. Both formulations were similarly well tolerated in all three studies. Overall, while formal bioequivalence cannot be concluded for all analytes, these data suggest therapeutic equivalence of the new formulation with the existing BDP/FF/GB pMDI formulation, therefore supporting reformulation using a propellant with low global warming potential.

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Abstract Background This study, in patients with symptomatic chronic obstructive pulmonary disease (COPD), explored switching therapy from non-extrafine high-dose inhaled corticosteroid/long-acting β 2 -agonist (ICS/LABA; fluticasone propionate/salmeterol [FP/SLM]) to extrafine medium-dose beclometasone dipropionate/formoterol fumarate dihydrate/glycopyrronium (BDP/FF/G), both via dry-powder inhaler. Functional Respiratory Imaging, a quantitative computed tomography method with 3D reconstructions of pulmonary anatomy, was used to assess airway geometry and lung function. Methods Patients receiving a stable ICS/LABA regimen for ≥ 8 weeks were switched to FP/SLM 500/50 µg, one inhalation twice-daily (high-dose ICS) for 6 weeks. After baseline assessments (Visit 2 [V2]), therapy was switched to BDP/FF/G 100/6/10 µg, two inhalations twice-daily (medium-dose ICS) for 6 weeks, followed by V3. The primary endpoints were percentage changes in specific image-based airway volume (siV aw ) and resistance (siR aw ) from baseline to predose at V3 (i.e., chronic effects), assessed at total lung capacity (TLC) in central and distal lung regions. Secondary endpoints included siV aw and siR aw changes from pre-dose to post-dose at V2, and from pre-dose to post-dose at V3 at TLC (i.e., acute effects), and chronic and acute changes in siV aw and siR aw at functional residual capacity (FRC). Pre-dose forced expiratory volume in 1 s (FEV 1 ) and COPD Assessment Test (CAT) were also assessed. Results There were no significant changes in pre-dose siV aw or siR aw at TLC from baseline to V3, although at FRC there was a significant decrease in mean siR aw in the distal airways (− 63.6%; p = 0.0261). In addition, in the distal airways there were significant acute effects at TLC on mean siV aw and siR aw (siV aw : 39.8% and 62.6%; siR aw : − 51.1% and − 57.2%, V2 and V3, respectively; all p &lt; 0.001) and at FRC at V2 (siV aw : 77.9%; siR aw : − 67.0%; both p &lt; 0.001). At V3, the mean change in pre-dose FEV 1 was 62.2 mL (p = 0.0690), and in CAT total score was − 3.30 (p &lt; 0.0001). Conclusions In patients with symptomatic COPD receiving high-dose ICS/LABA, adding a long-acting muscarinic antagonist while decreasing the ICS dose by switching to medium-dose extrafine BDP/FF/G was associated with improved airway indices, especially in the distal airways, together with improvements in respiratory health status. Trial registration ClinicalTrials.gov (NCT04876677), first posted 6th May 2021

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