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Clinical Drug Investigation Sep 2022The source data of four individual randomised, double-blind, reference- and/or placebo-controlled clinical trials with virtually identical study design were pooled for... (Meta-Analysis)
Meta-Analysis
Efficacy and Safety of a Fixed-Dose Combination of Cinnarizine 20 mg and Dimenhydrinate 40 mg in the Treatment of Patients with Vestibular Vertigo: An Individual Patient Data Meta-Analysis of Randomised, Double-Blind, Controlled Clinical Trials.
BACKGROUND AND OBJECTIVE
The source data of four individual randomised, double-blind, reference- and/or placebo-controlled clinical trials with virtually identical study design were pooled for the present meta-analysis. The main objective was to further evaluate the efficacy and safety of the fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg in comparison to various other antivertigo treatments in patients suffering from central and/or peripheral vestibular vertigo.
METHODS
Adult male and female outpatients were subjected to a 4-week treatment with the fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg, cinnarizine (20 mg, 50 mg), dimenhydrinate (40 mg, 100 mg), betahistine dimesylate (12 mg), betahistine dihydrochloride (16 mg) and placebo, respectively. The primary efficacy endpoint was the reduction of a validated mean vertigo score (MVS), a composite score of 12 individual vertigo symptoms, the intensities of which were each evaluated by the patients on a 5-point visual analogue scale. For analysis of primary and further secondary efficacy endpoints, baseline-adjusted analysis of covariance (ANCOVA) was used to calculate adjusted least squares means (LSM) with associated two-sided 95% confidence intervals (CIs) for the difference in MVS reductions between treatment groups. Moreover, various sensitivity analyses, responder and subgroup analyses as well as descriptive analyses with respect to safety/tolerability of the treatments were conducted.
RESULTS
Of 795 randomised patients, 779 belonged to the intent-to treat (ITT) and 723 to the per-protocol (PP) population. The main efficacy analysis was based on the ITT population (mean age 52.1 years, 61% female). The mean decrease of the MVS from baseline to Week 4 in the cinnarizine/dimenhydrinate group (-1.10) proved to be significantly larger than in any of the comparator groups. LSM differences for comparators versus the fixed combination ranged between 0.16 (95% confidence interval (CI) 0.03; 0.30, p = 0.017) for cinnarizine 20 mg and 0.60 (95% CI 0.42; 0.78; p < 0.001) for betahistine dimesylate 12 mg in favour of the fixed combination. Furthermore, after 4 weeks of treatment, 74 patients (24.7%) in the cinnarizine/dimenhydrinate group were completely symptom free (MVS = 0), a significantly greater proportion than in any of the comparator groups. Sensitivity analyses showed that baseline characteristics such as age, sex, duration of vertigo and antivertigo pretreatment had only a very minor and clinically non-relevant impact on the efficacy results regarding the primary efficacy outcome. Subgroup analyses with respect to age groups (< 65 years/≥ 65 years) and sex showed no significant differences in efficacy within any of the treatment groups. All treatments were well tolerated. A total of 55 patients (6.9%) reported 75 non-serious adverse events (AEs), and 19 patients (2.4%) discontinued the study prematurely because of AEs. Nearly 95% of the patients (cinnarizine/dimenhydrinate group: 97.9%) rated the tolerability of the study medications as either "good" or "very good".
CONCLUSION
The findings of the present meta-analysis indicate that the fixed combination of cinnarizine and dimenhydrinate is a safe and potentially superior treatment option for patients suffering from central and/or peripheral vestibular vertigo, as compared to current standard treatments such as cinnarizine, dimenhydrinate or betahistine given alone in monotherapy.
Topics: Adult; Aged; Betahistine; Cinnarizine; Dimenhydrinate; Double-Blind Method; Female; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; Vertigo
PubMed: 35864302
DOI: 10.1007/s40261-022-01184-0 -
Brazilian Journal of Biology = Revista... 2022Chrozophora tinctoria (L.) A.Juss. is herbaceous, monecious annual plant used traditionally to cure gastrointestinal disorders. The present study was carried out to find...
Chrozophora tinctoria (L.) A.Juss. is herbaceous, monecious annual plant used traditionally to cure gastrointestinal disorders. The present study was carried out to find the bioactive compounds by Gas Chromatography-Mass Spectrometry, the acetylcholinesterase inhibitory potential acute toxicity, and emetic activity present in the ethyl acetate fraction of Chrozophora tinctoria (EAFCT) and dichloromethane fraction of Chrozophora tinctoria (DCMFCT). The compounds detected in both fractions were mostly fatty acids, with about seven compounds in EAFCT and 10 in DCMFCT. These included pharmacologically active compounds such as imipramine, used to treat depression, or hexadecanoic acid methyl ester, an antioxidant, nematicide, pesticide, hypocholesterolemic, 9,12,15-Octadecatrienoic acid, ethyl ester, (Z,Z,Z)- is used as a cancer preventive, antiarthritic, antihistaminic, hepatoprotective, insectifuge, nematicide, Pentadecanoic acid, 14-methyl-, methyl ester have antifungal, antimicrobial and antioxidant activities, 10-Octadecanoic acid, methyl ester have the property to decrease blood cholesterol, Antioxidant and antimicrobial, 1-Eicosanol is used as an antibacterial, 1-Hexadecene has antibacterial, antioxidant, and antifungal activities. Both DCMFCT and EAFCT fractions inhibited acetylcholinesterase (AChE) activity with IC50 values of 10 µg and 130 µg, respectively. Both the fractions were found to be toxic in a dose-dependent manner, inducing emesis at 0.5g onward and lethargy and mortality from 3-5 g upwards. Both the fractions combined with distilled water showed highly emetic activity. The significant increase in the number of vomits was shown by EAFCT plus distilled water which are 7.50±1.29, 7.25±3.10, and 11.75±2.22 number of vomits at 1g, 2g, and 3g/kg concentration respectively, while DCMFCT plus distilled water showed 5.25±2.22, 7.50±2.52 and 10.25±2.22 number of vomits at 1g, 2, and 3g/kg correspondingly. The antiemetic standard drug metoclopramide has a higher impact against the emesis induced by both the fractions than dimenhydrinate. Metoclopramide decreases the number of vomits caused by EAFCT to 1.00±0.00, 2.00±0.00, 4.00±1.00 at 1g, 2, and 3g/kg sequentially, while dimenhydrinate decreases the number of vomits to 1.33±0.58, 2.33±1.15, 4.33±0.58 at 1g, 2, and 3g respectively. In the same way, Metochloprimide decreases the number of emesis caused by DcmCt from 5.25±2.22, 7.50±2.52, 10.25±2.22 to 1.33±0.58, 2.33±1.1, 4.33±0.58 at 1g, 2, and 3g/kg concentrations. The present study is the first documented report that scientifically validates the folkloric use of Chrozophora tinctoria as an emetic agent.
Topics: Acetylcholinesterase; Animals; Anti-Bacterial Agents; Antifungal Agents; Antioxidants; Dimenhydrinate; Emetics; Esters; Euphorbiaceae; Gas Chromatography-Mass Spectrometry; Metoclopramide; Models, Animal; Plant Extracts; Vomiting; Water
PubMed: 35613215
DOI: 10.1590/1519-6984.260566 -
Wilderness & Environmental Medicine Jun 2022Acute altitude exposure is a common event in Latin America that can result in mild to severe altitude illness. Medical students from some Latin American countries...
INTRODUCTION
Acute altitude exposure is a common event in Latin America that can result in mild to severe altitude illness. Medical students from some Latin American countries receive little information on this topic. Our aim was to determine the knowledge and incidence of acute mountain sickness (AMS), as well as the methods used to prevent AMS among medical students attending the Pan-American Student Meeting in Cusco, Peru, a city at high altitude (3400 m).
METHODS
We conducted a cross-sectional study on medical students attending a conference. Participants completed a questionnaire on the day of registration that collected demographic data and investigated students' knowledge of AMS, its prophylaxis, and their personal experience of symptoms.
RESULTS
A total of 840 students attended the meeting. Two hundred eighty-eight returned surveys, 51 from high altitude locations. Respondent age was 23±3 y (mean±SD), and 72% were female. Thirty-two percent had basic knowledge about symptoms of AMS. Headache was recognized as a symptom by 79%. Knowledge of AMS prophylaxis was reported by 70%. Coca leaf products and dimenhydrinate were mentioned by 30 and 16%, respectively, whereas acetazolamide was recognized by only 10% of participants. AMS incidence was 42%. Prophylactic measures were adopted by 47% of the participants in our study. Thirty-six percent used dimenhydrinate and 27% used coca tea. Less than 1% used acetazolamide as recommended.
CONCLUSIONS
We found poor knowledge of AMS and effective prophylaxis among medical students from several South American countries traveling to 3400 m.
Topics: Acetazolamide; Acute Disease; Altitude Sickness; Cross-Sectional Studies; Dimenhydrinate; Female; Humans; Latin America; Male; Students, Medical
PubMed: 35361528
DOI: 10.1016/j.wem.2021.12.004 -
Journal of AOAC International Jun 2022Reverse phase liquid chromatography (RP-LC) is considered the most extensively used chromatographic technique in drug separation and quantification, yet its routine use...
Simple Eco-Friendly RP-LC Method for the Synchronous Separation of Six Widely Used Drugs in the Treatment of Cerebrovascular and Vestibular Disorders: Application for Analysis in Their Single and Combined Drug Products.
BACKGROUND
Reverse phase liquid chromatography (RP-LC) is considered the most extensively used chromatographic technique in drug separation and quantification, yet its routine use shows increasing environmental challenges about energy consumption, solvent used, and waste engendered. From this perception, efforts for greening the developed RP-LC methods are focused on using green solvents and reducing the amount of solvent used and waste produced.
OBJECTIVE
The target of this work is to develop an eco-friendly RP-LC method for the synchronous separation of six widely used drugs in the treatment of cerebrovascular and vestibular disorders, namely neurotropic piracetam, antihistamines dimenhydrinate, cinnarizine, and fluranizine, and vasodilators vincamine and vinpocetine.
METHOD
Separation and quantification are accomplished at ambient temperature by isocratic elution mode using acetonitrile-0.2% triethylamine (85:15 by volume) as a mobile phase at a flow rate of 1.5 mL/min on a Hypersil C18 column. UV detection and quantification are carried out at 225 nm.
RESULTS
The method is fully validated per ICH guidelines, where all analytical parameters are within the acceptable range (r > 0.9999), accuracy (≥99.55%), and precision (0.02-0.97%).
CONCLUSIONS
The method is applied for the routine analysis of the cited drugs in their single and combined drug products, and it is considered excellent in terms of greenness with respect to Eco-Scale assessment.
HIGHLIGHTS
As the routine use of the RP-LC technique shows increasing environmental challenges, efforts for greening are attempted focusing on the use of green solvents and reducing the amount of solvent used and waste produced. A simple eco-friendly RP-LC method for the synchronous separation of six widely used drugs in the treatment of cerebrovascular and vestibular disorders is developed. The method is fully validated per ICH guidelines, where all analytical parameters are within the acceptable range. The method is applied for the routine analysis of the cited drugs in their single and combined drug products.
Topics: Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Solvents
PubMed: 35167683
DOI: 10.1093/jaoacint/qsac021 -
Deutsches Arzteblatt International May 2022Nausea and vomiting are common and distressing side effects of tumor therapy. Despite prophylaxis, 40-50% of patients suffer from nausea, and 20-30% from vomiting....
BACKGROUND
Nausea and vomiting are common and distressing side effects of tumor therapy. Despite prophylaxis, 40-50% of patients suffer from nausea, and 20-30% from vomiting. Antiemetic prophylaxis and treatment are therefore of great importance for improving patients' quality of life and preventing sequelae such as tumor cachexia.
METHODS
The recommendations presented here are based on international and national guidelines, updated with publications retrieved by a selective search in the PubMed and Cochrane Library databases, with special attention to randomized controlled trials and meta-analyses that have appeared in the past 5 years since the German clinical practice guideline on supportive therapy was published.
RESULTS
Risk-adjusted prevention and treatment is based on the identification of treatment-related and patient-specific risk factors, including female sex and younger age. Parenteral tumor therapy is divided into four risk classes (minimal, low, moderate, high), and oral tumor therapy into two (minimal/low, moderate/high). In radiotherapy, the radiation field is of decisive importance. The antiemetic drugs most commonly used are 5-HT3-RA, NK1-RA, and dexamethasone; olanzapine has proven beneficial as an add-on or rescue drug. The use of steroids in patients being treated with drug combinations including checkpoint inhibitors is discussed controversially because of the potentially reduced therapeutic response. Benzodiazepines, dimenhydrinate, and cannabinoids can be used as backup antiemetics. Acupuncture/acupressure, ginger, and progressive muscle relaxation are pos - sible alternative methods.
CONCLUSION
Detailed, effective, risk profile-adapted algorithms for the prevention and treatment of nausea and vomiting are now available for patients undergoing classic chemotherapy regimens or combined radiotherapy and chemotherapy. Optimal symptom control for patients undergoing oral tumor therapy over multiple days in the outpatient setting remains a challenge.
Topics: Antiemetics; Antineoplastic Agents; Female; Humans; Mouth Neoplasms; Nausea; Quality of Life; Vomiting
PubMed: 35140010
DOI: 10.3238/arztebl.m2022.0093 -
Canadian Geriatrics Journal : CGJ Dec 2021Older age increases the likelihood of chronic diseases and polypharmacy with the likelihood of potentially inappropriate medications (PIMs) in secondary and tertiary...
BACKGROUND
Older age increases the likelihood of chronic diseases and polypharmacy with the likelihood of potentially inappropriate medications (PIMs) in secondary and tertiary care levels, but in the primary care settings of Thailand there still is a need for more evidence. This study aimed to examine the prevalence of PIM in primary care settings, and to identify factors that influence the use of PIM.
METHODS
A cross-sectional retrospective study was conducted in 2017. Eight primary care units from four regions of Thailand were randomly selected. People aged ≥ 60 years in the eight units were studied as participants. The List of Risk Drugs for Thai Elderly (LRDTE) was used as the reference. Multivariate logistic regression was carried out to identify factors that influence.
RESULTS
A total of 4,848 patients aged ≥60 years with 20,671 prescriptions were studied. The mean age was 70.7±8.3 years for males, and 61.2% for females. A little more than 5% (5.1%) had ≥ 3 chronic diseases and 15.0% received polypharmacy (≥5 medications). The prevalence of prescriptions with PIMs was 65.9%. The most frequent PIMs were antidepressants: amitriptyline (28.1%), antihistamines: dimenhydrinate (22.4%) and chlorpheniramine maleate (CPM) (11.2%); and Benzodiazepines: lorazepam (6.5%). Three factors that significantly influenced prescribing of PIMs were polypharmacy (adjusted OR 3.51; 95% CI 2.81-4.32), having ≥3 chronic diseases (adjusted OR 1.44; 95% CI 1.04-2.01), and age ≥75 years (adjusted OR 1.18; 95% CI 1.01-1.38).
CONCLUSION
More than two-thirds of elderly Thai patients in the primary care settings were prescribed PIMs. Multidisciplinary prescription review and PIM screening in patients aged ≥75 years who have ≥3 chronic diseases or polypharmacy should be implemented in primary care and supportive computerized PIMs alert system is needed.
PubMed: 34912488
DOI: 10.5770/cgj.24.516 -
Brazilian Journal of Anesthesiology... 2024We tested the hypothesis that, within the margin of 15% of risk difference, palonosetron is not inferior to ondansetron in reducing the incidence of postoperative nausea... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
We tested the hypothesis that, within the margin of 15% of risk difference, palonosetron is not inferior to ondansetron in reducing the incidence of postoperative nausea and vomiting (PONV) in laparoscopic cholecystectomy.
METHODS
We conducted a double-blind, non-inferiority, randomized, controlled trial of 212 patients aged 18 to 65 years undergoing laparoscopic cholecystectomy under general anesthesia in two secondary care hospitals. Patients were randomly assigned to receive either palonosetron (0.075.ßmg) or ondansetron (8.ßmg) intravenously at induction of anesthesia. Ondansetron (8.ßmg) was also administered 8 and 16.ßhours postoperatively. All anesthetic and surgical procedures were standardized. Patients were evaluated for 24.ßhours postoperatively for the occurrence of PONV.
RESULTS
A high incidence of PONV was observed at 2...6.ßhours postoperatively, with a rate of 36.8% (95% confidence interval [CI] 28.2...46.3) in the palonosetron group, as compared to 43.4% (95% CI 34.4...52.9) in the ondansetron group. The risk difference (95% CI) between palonosetron and ondansetron for PONV was 0 (-10.9 to 10.9) at 0...2.ßhours, -6.6 (-19.4 to 6.5) at 2...6.ßhours, -0.9 (-11.0 to 9.2) at 6...12.ßhours, and -2.8 (-9.6 to 3.6) at 12...24.ßhours. There was no statistically significant difference between the palonosetron and ondansetron groups in the use of rescue medication (dimenhydrinate). There were no adverse events associated with the medications under study.
CONCLUSION
Palonosetron is not inferior to ondansetron in patients at risk of PONV undergoing laparoscopic cholecystectomy, providing a good option for PONV prophylaxis, as it can be administered in a single dose.
Topics: Humans; Ondansetron; Palonosetron; Postoperative Nausea and Vomiting; Antiemetics; Cholecystectomy, Laparoscopic; Treatment Outcome; Anesthesia, General; Double-Blind Method
PubMed: 34280455
DOI: 10.1016/j.bjane.2021.06.020 -
Pakistan Journal of Pharmaceutical... Jan 2021Development of dimenhydrinate (DMN) emulgel formulation has been described in this work with enhanced permeation for transdermal delivery of DMN for effective management...
Development of dimenhydrinate (DMN) emulgel formulation has been described in this work with enhanced permeation for transdermal delivery of DMN for effective management of motion sickness. Various DMN emulgel formulations were prepared using central composite design in response surface methodology. Propylene glycol and olive oil were used in varying ratios as permeation enhancers along-with carbopol-934 as gelling agent. Prepared formulations were evaluated by physico-chemical properties, stability and Fourier transform infrared spectroscopy (FTIR) studies. In-vitro drug release was studied using cellophane membrane. Formulation F2 showed maximum drug permeation following diffusion-based release mechanism and was used in further studies. Rat skin was used in Franz cell for ex-vivo studies to determine various permeation kinetic parameters. FTIR studies provided no evidence of chemical interaction between DMN and polymers used, whereas molecular docking revealed formation of a stable complex in the presence of aqueous environment with stable intermolecular binding and the complex was well hydrated. No evidence of skin irritation was observed in human volunteers following application of the optimized formulation. Histopathology data of the rat skin showed a decreased proliferation of the lymphocytes whereas monocytes were induced. In conclusion, combination of propylene glycol and olive oil was successfully employed for delivery of DMN through transdermal route with good permeability and prolonged release time that can be highly beneficial in treating motion sickness in unusual circumstances.
Topics: Administration, Cutaneous; Animals; Antiemetics; Dimenhydrinate; Drug Delivery Systems; Emulsions; Gels; Molecular Docking Simulation; Motion Sickness; Olive Oil; Propylene Glycol; Rats; Skin; Skin Absorption; Spectroscopy, Fourier Transform Infrared
PubMed: 34275848
DOI: No ID Found -
Frontiers in Neurology 2021The Mean Vertigo Score (MVS) is a composite score for defining the burden of disease of patients suffering from vestibular disorders. It has been used in clinical...
The Mean Vertigo Score (MVS) is a composite score for defining the burden of disease of patients suffering from vestibular disorders. It has been used in clinical research for about 30 years. This study investigates discriminant validity of the MVS and describes structural relationships of the 12 single criteria used for construction of the MVS. The statistical analyses are based on the raw data of an earlier conducted randomized, doubleblind, placebo-controlled clinical trial, which compared the following four randomized treatment groups: a fixed combination of cinnarizine and dimenhydrinate (Arlevert), two groups with only one of the two study drugs, and a group with placebo. The method used for the statistical calculations is the Wei-Lachin procedure, a multivariate generalization of the Mann-Whitney test, which takes into account correlations among the 12 single symptoms of the composite score. All 12 single symptoms of the composite endpoint proved to be useful for detecting differences (Mann-Whitney effect size measures: 0.58-0.73) and thus for discriminating between treatment groups. Their Pearson product-moment correlations are all positive (range 0.07-0.71) and point to the same direction, which indicates one-dimensionality and good internal consistency of the composite index MVS. Furthermore, our statistical calculations revealed that successively increasing the number of single items of the MVS to up to twelve enhances its reliability ( = 0.923), which leads to a substantially higher test power and reduction of the number of patients needed (sample size) in a clinical trial. The use of the multivariate Wei-Lachin procedure provides further evidence of the validity of the 12-item composite score MVS, based on the efficacy data of its 12 single vertigo symptoms. The present findings demonstrate that the MVS is a powerful tool, which can be used to adequately describe the patients' self-perceived vertigo complaints, both qualitatively and quantitatively. It may therefore be regarded as a clinically meaningful alternative to other questionnaires that are presently used in vestibular research.
PubMed: 34025547
DOI: 10.3389/fneur.2021.601749