FAS-IN-1 Tosylate

Efficacy and safety of remimazolam tosylate in hysteroscopy: A randomized, single-blind, parallel controlled trial

What is known and objective: To compare the effectiveness and safety of remimazolam tosylate and propofol for hysteroscopy. Methods: From November 2020 to June 2021, a total of 90 patients who underwent hysteroscopy were prospectively enrolled in this study. The patients were randomly assigned to three groups: propofol group (group A), low-dose remimazolam tosylate group (group B), and high-dose remimazolam tosylate group (group C), with 30 cases in each group. All cases received intravenous sufentanil 0.1ug/kg for analgesic preconditioning. Patients in group A were given 2 mg/kg propofol intravenously, and maintained at a rate of 5 mg/kg/h. Patients in groups B and C were given intravenous remimazolam tosylate 0.25 mg/kg. Group B was maintained with remimazolam tosylate at a rate of 0.48 mg/kg/h, while group C was at a rate of 0.6 mg/kg/h. The changes of heart rate (HR), mean arterial pressure (MAP) and saturation of peripheral oxygen (SpO2) were recorded after admission (T0), 1 min after anaesthesia (T1), dilation of the uterine cavity (T2), and the end of hysteroscopy (T3). In addition, Observer's Assessment of Alertness/Sedation Scale (OAA/S) at 1 min, 3 min, and 5 min after hysteroscopy, the incidence of adverse events, and the time from the end of the hysteroscopy to reach the discharge standard, were recorded. Results and discussion: The success rate of sedation in each group was 100%. After administration, the adverse event incidence in group A was significantly higher than that in groups B and C (p < 0.05, respectively). Compared with propofol, remimazolam tosylate did not cause injection pain, had less impact on haemodynamics and caused less respiratory depression. What is new and conclusion: Remimazolam tosylate and propofol have similar success rates for painless hysteroscopy, and both can provide safe and effective sedation. The safety of remimazolam tosylate for hysteroscopy appears to be better than that of propofol.

Topical Glycopyrronium Tosylate in Primary Axillary Hyperhidrosis: A Profile of Its Use

Glycopyrronium tosylate (Qbrexza^?) is available as single-use, pre-moistened cloths and has been approved in the USA for the topical treatment of primary axillary hyperhidrosis in adults and children ≥ 9 years of age. Glycopyrronium tosylate is effective in reducing patient-reported severity of disease and gravimetrically measured sweat production in this patient population; improvements have been shown to be maintained throughout long-term treatment (up to 48 weeks). Glycopyrronium tosylate is generally well tolerated, with most adverse events being mild to moderate in severity. Glycopyrronium tosylate thus provides a self-administered, non-invasive alternative to topical antiperspirant therapy and clinic-based treatments in adults with primary axillary hyperhidrosis, and is the only alternative to topical antiperspirants specifically approved in children and adolescents ≥ 9 years of age.

Topical glycopyrronium tosylate in Japanese patients with primary axillary hyperhidrosis: A randomized, double-blind, vehicle-controlled study

Glycopyrronium tosylate cloth, an anticholinergic drug, has been approved for the topical treatment of primary axillary hyperhidrosis in the USA, but its effects in Japanese patients have not been previously investigated. This 4-week, randomized, double-blind, vehicle-controlled, multicenter study was conducted to evaluate the efficacy and safety of glycopyrronium tosylate cloth for primary axillary hyperhidrosis patients in Japan. Eligible patients, who were ≥9 years of age and had primary axillary hyperhidrosis ≥6 months, with gravimetrically-measured sweat production ≥50 mg/5 min, and Hyperhidrosis Disease Severity Scale ≥3 (moderate) were randomized 1:1:1 to once daily topical glycopyrronium tosylate 3.75%, 2.5%, or vehicle. Overall, 497 patients (163 in the glycopyrronium tosylate 3.75% group, 168 in the glycopyrronium tosylate 2.5% group, and 166 in the vehicle group, hereinafter in this order) were randomized. Statistically higher proportions of patients in the glycopyrronium tosylate groups achieved ≥2-point improvement in Hyperhidrosis Disease Severity Scale and ≥50% reduction in sweat production from baseline versus vehicle at week 4 (51.6%, 41.1%, and 16.4%, respectively; p < 0.001 in both cases). Higher responder rates in the glycopyrronium tosylate groups compared with the vehicle group occurred as early as week 1. The most common treatment-emergent adverse events in patients treated with glycopyrronium tosylate were photophobia, mydriasis, thirst, and dysuria. Most treatment-emergent adverse events were mild as determined by the investigators. The incidence of treatment-emergent adverse events leading to treatment modification was low in the three groups. The 4-week use of topical glycopyrronium tosylate improved the patient-reported outcome measure Hyperhidrosis Disease Severity Scale and objectively-evaluated sweat production with a favorable benefit/risk profile.

Structural Polymorphism of Sorafenib Tosylate as a Key Factor in Its Solubility Differentiation

The presence of active pharmaceutical ingredients (APIs) in the forms of different polymorphic states can induce differences in their physicochemical properties. In the case of poorly soluble APIs, like the oncological drug sorafenib tosylate, small variations in solubility may result in large bioavailability differences. The control of its therapeutic dose is crucial from the effective pharmacotherapy point of view and the reduction of side effects. Therefore, this study aimed to assess the influence of sorafenib tosylate polymorphic forms on its solubility and, consequently, permeability, based on passive diffusion through membranes simulating the gastrointestinal tract (GIT) conditions. In the first part of the work, two crystalline forms of sorafenib tosylate were identified using the X-ray powder diffraction, FT-IR, and Raman spectroscopy. Subsequently, solubility studies were carried out. Both forms of sorafenib tosylate were insoluble in 0.1 N hydrochloric acid (HCl), in acetate buffer (pH 4.5), and in phosphate buffer (pH 6.8). Solubility (mg/mL) of form I and III of sorafenib tosylate in 0.1 N HCl + 1.0% SDS was 0.314 ± 0.006 and 1.103 ± 0.014, respectively, in acetate buffer pH 4.5 + 1.0% SDS it was 2.404 ± 0.012 and 2.355 ± 0.009, respectively, and in phosphate buffer pH 6.8 + 1.0% SDS it was 0.051 ± 0.005 and 1.805 ± 0.023, respectively. The permeability study was assessed using the parallel artificial membrane permeability assay (PAMPA) model. The apparent permeability coefficient (P_app-cm s^-1) of form I and III in pH 1.2 was 3.01 × 10^-5 ± 4.14 × 10^-7 and 3.15 × 10^-5 ± 1.89 × 10^-6, respectively, while in pH 6.8 it was 2.72 × 10^-5 ± 1.56 × 10^-6 and 2.81 × 10^-5 ± 9.0 × 10^-7, respectively. Changes in sorafenib tosylate concentrations were determined by chromatography using the high-performance liquid chromatography (HPLC)-DAD technique. As a result of the research on the structural polymorphism of sorafenib tosylate, its full spectral characteristics and the possibility of using FT-IR and Raman spectroscopy for the study of polymorphic varieties were determined for the first time, and the HPLC method was developed, which is appropriate for the assessment of sorafenib solubility in various media. The consequences of various physicochemical properties resulting from differences in the solubility of sorafenib tosylate polymorphs are important for pre-formulation and formulation studies conducted with its participation and for the safety of oncological sorafenib therapy.

Lumateperone tosylate, A Selective and Concurrent Modulator of Serotonin, Dopamine, and Glutamate, in the Treatment of Schizophrenia

Purpose of review: This is a comprehensive review of the literature regarding the use of Lumateperone tosylate for schizophrenia. This review presents the background, evidence, and indications for the use of lumateperone tosylate in the treatment of schizophrenia.
Recent findings: Schizophrenia is a chronic mental health disorder that affects approximately 3.3 million people in the United States. Its symptoms, which must be present more than six months, are comprised of disorganized behavior and speech, a diminished capacity to comprehend reality, hearing voices unheard by others, seeing things unseen by others, delusions, decreased social commitment, and decreased motivation. The majority of these symptoms can be managed with antipsychotic medication. Lumateperone is a selective and concurrent modulator of serotonin, dopamine, and glutamate, which all mediate or modulate serious mental illness.
Summary: Schizophrenia is a complex, severe mental illness that affects how the brain processes information. There are many medications used to treat schizophrenia. One antipsychotic agent, lumateperone tosylate, is a newer agent that the FDA recently approved. The most common adverse effects are shown to be mild such as somnolence, constipation, sedation, and fatigue, with the 42 mg recommended dose. Lumateperone tosylate is an FDA-approved drug that can be given only at the 42mg dose once daily with no titration requirements.