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The Medical Letter on Drugs and... Oct 2019
Review
Topics: Animals; Antimalarials; Diarrhea; Humans; Insect Bites and Stings; Malaria; Travel; Travel-Related Illness
PubMed: 31599872
DOI: No ID Found -
Clinical Drug Investigation Nov 2019Vertigo derived from peripheral vestibular disorders is quite frequently encountered in daily clinical practice and can be a severely disabling symptom associated with... (Comparative Study)
Comparative Study Randomized Controlled Trial
Efficacy and Safety of a Fixed Combination of Cinnarizine 20 mg and Dimenhydrinate 40 mg vs Betahistine Dihydrochloride 16 mg in Patients with Peripheral Vestibular Vertigo: A Prospective, Multinational, Multicenter, Double-Blind, Randomized, Non-inferiority Clinical Trial.
BACKGROUND AND OBJECTIVE
Vertigo derived from peripheral vestibular disorders is quite frequently encountered in daily clinical practice and can be a severely disabling symptom associated with substantial impairment of health-related quality of life for the affected patients. Betahistine, a structural analogue of histamine and presumably the most widely prescribed anti-vertigo drug worldwide, has previously been shown to be an effective and safe treatment for these patients. The objective of the present study was to evaluate whether the fixed combination of cinnarizine and dimenhydrinate (Arlevert) is non-inferior and thus a potentially useful alternative to betahistine dihydrochloride in the treatment of patients suffering from peripheral vestibular vertigo.
METHODS
In this prospective, multicenter, double-blind, randomized, non-inferiority clinical trial, outpatients from 8 ENT clinics in Austria, Bulgaria, the Czech Republic and Russia were randomly assigned to receive three times daily one tablet of either the fixed combination cinnarizine 20 mg/dimenhydrinate 40 mg or betahistine dihydrochloride 16 mg for 4 weeks. Primary endpoint was the reduction of the mean vertigo score (MVS), a validated 12-item composite score defined as the mean of 6 vertigo symptoms (dystasia and walking unsteadiness, staggering, rotary sensation, tendency to fall, lift sensation, blackout) and 6 trigger factors for vertigo (change of position, bowing, getting up, driving by car/train, head movements, eye movement), after 4 weeks of therapy, as judged by the patient on a 5-point visual analogue scale (VAS). The non-inferiority margin was set to 0.3. Secondary outcomes included the patient's and investigator's judgment of global efficacy, the patient's rating of impairment of daily activities, and safety/tolerability of the treatments.
RESULTS
Three hundred and six patients (mean age 53.5 years, approximately 60% female) were enrolled and randomized to the fixed combination cinnarizine/dimenhydrinate (n = 152) or betahistine (n = 154) groups; 297 patients completed the study and 294 (146 and 148, respectively) were valid for the per-protocol analysis, which was used for the non-inferiority analysis. Treatment with cinnarizine/dimenhydrinate led to a stronger reduction of the MVS [least squares mean (LSM)] after 4-week therapy (primary endpoint) in comparison to betahistine (0.395 vs 0.488; difference: - 0.093, 95% CI - 0.180; - 0.007, p = 0.035); since the upper limit of the two-sided 95% confidence interval was not only below the non-inferiority margin of 0.3, but also entirely below 0, superiority of the fixed combination could be demonstrated. The combination preparation was also more effective after 1 week of therapy and received more favorable patient's ratings on overall efficacy and impairment of daily activities. Both treatments were very well tolerated. Only 12 patients (3.92%) reported 13 non-serious adverse events; 2 cinnarizine/dimenhydrinate-treated patients discontinued the study prematurely due to adverse events as compared to 5 betahistine-treated patients.
CONCLUSION
The fixed combination of cinnarizine 20 mg and dimenhydrinate 40 mg was found to be not only non-inferior, but superior to betahistine 16 mg in the improvement of peripheral vestibular vertigo. Furthermore, taking into account a good and slightly favorable safety profile, the present study provides evidence that the fixed-combination preparation is a potent and even superior alternative to betahistine in the treatment of vertigo related to peripheral vestibular disorders.
STUDY REGISTRATION
EudraCT No. 2011-004025-27.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Betahistine; Cinnarizine; Dimenhydrinate; Double-Blind Method; Drug Combinations; Female; Humans; Male; Middle Aged; Prospective Studies; Vertigo; Young Adult
PubMed: 31571128
DOI: 10.1007/s40261-019-00858-6 -
BMJ Quality & Safety Dec 2019Benzodiazepines and sedative hypnotics (BSH) have numerous adverse effects that can lead to negative outcomes, particularly in vulnerable hospitalised older adults. At... (Comparative Study)
Comparative Study
BACKGROUND
Benzodiazepines and sedative hypnotics (BSH) have numerous adverse effects that can lead to negative outcomes, particularly in vulnerable hospitalised older adults. At our institution, over 15% of hospitalised older adults are prescribed sedative-hypnotics inappropriately. Of these prescriptions, 87% occurred at night to treat insomnia and almost 20% came from standard admission order sets.
METHODS
We conducted a time-series study from January 2015 to August 2016 among medical and cardiology inpatients following the implementation in August 2015 of a sedative reduction bundle (education, removal of BSH from available admission order sets and non-pharmacological strategies to improve sleep). Preintervention period was January-July 2015 and postintervention period was August 2015-August 2016. A surgical ward served as control. Primary outcome was the proportion of BSH-naive (not on BSH prior to admission) patients 65 years or older discharged from medical and cardiology wards who were prescribed any new BSH for sleep in hospital. Data were analysed on statistical process control (SPC) p-charts with upper and lower limits set at 3δ using standard rules. Secondary measures included Patient-reported Median Sleep Quality scores and rates of fall and sedating drug prescriptions that may be used for sleep (dimenhydrinate).
RESULTS
During the study period, there were 5805 and 1115 discharges from the intervention and control units, respectively. From the mean baseline BSH prescription rate of 15.8%, the postintervention period saw an absolute reduction of 8.0% (95% CI 5.6% to 10.3%; p<0.001). Adjusted for temporal trends, the intervention produced a 5.3% absolute reduction in the proportion of patients newly prescribed BSH (95% CI 5.6% to 10.3%; p=0.002). BSH prescription rates remained stable on the control ward. Patient-reported measure of sleep quality, falls and use of other sedating medications remained unchanged throughout the study duration.
CONCLUSION
A comprehensive intervention bundle was associated with a reduction in inappropriate BSH prescriptions among older inpatients.
Topics: Aged; Aged, 80 and over; Drug Utilization; Female; Health Education; Health Personnel; Hospitalization; Hospitals, University; Humans; Hypnotics and Sedatives; Inpatients; Male; Ontario; Prescription Drug Misuse; Sleep Initiation and Maintenance Disorders
PubMed: 31270252
DOI: 10.1136/bmjqs-2018-009241 -
Drug Delivery and Translational Research Oct 2019The objective of the study was the development and in vitro characterization of a self-emulsifying drug delivery system (SEDDS) for the nasal application of...
The objective of the study was the development and in vitro characterization of a self-emulsifying drug delivery system (SEDDS) for the nasal application of dimenhydrinate. Final composition of SEDDS was established based on drug solubility and stability studies. Dimenhydrinate was loaded into the SEDDS pre-concentrates to 7.5% (m/v). The droplet size of the final SEDDS formulations was in a range between 60 and 220 nm. Permeability, as well as tissue toxicity, of the formulations was investigated using bovine nasal mucosa. Enhancement in permeation up to 2.8-fold compared to pure dimenhydrinate was confirmed. Furthermore, toxicity studies did not reveal any serious tissue damages related to the SEDDS. Additionally, irritation potential of SEDDS was evaluated in ciliary beat frequency measurements. Incorporation of dimenhydrinate into SEDDS might therefore be considered as a promising approach within the field of nasal delivery of antiemetics by utilizing permeation enhancement strategy.
Topics: Administration, Intranasal; Animals; Antiemetics; Cattle; Cilia; Dimenhydrinate; Drug Delivery Systems; Drug Liberation; Emulsions; In Vitro Techniques; Nasal Mucosa; Permeability; Solubility
PubMed: 30877627
DOI: 10.1007/s13346-019-00634-1 -
Journal of Addiction Medicine 2019: Reporting of intoxication and withdrawal from aberrant use of over-the-counter medication has been sparse and inconsistent in literature. Attributed to their...
: Reporting of intoxication and withdrawal from aberrant use of over-the-counter medication has been sparse and inconsistent in literature. Attributed to their anticholinergic properties, medications such as dimenhydrinate (Gravol) taken in supratherapeutic doses have been associated with euphoria, anxiolysis, and hallucinations. We present a case of a woman in her forties, with a psychiatric history of bipolar disorder, and complex concurrent medical history including familial Mediterranean fever (FMF), and fibromyalgia, admitted for withdrawal management of her intravenous dimenhydrinate use. As a result of her FMF, there were numerous hospital admissions and treatment which required intravenous access. Hence, a physician-inserted intravenous access port was placed on her chest. The port was maintained monthly with the help of a community agency. In this port, she was injecting 100 to 200 mg of dimenhydrinate hourly for its euphoric and calming effects, consuming upwards of 2400 mg/d. Comprehensive laboratory work-up and urine drug screening were unremarkable. Vital signs were stable. Her mental status at time of admission was lethargic, unfocused, but calm. Her withdrawal symptoms included severe nausea, vomiting, sedation, headaches, dizziness, anxiety, and muscle stiffness. Her detoxification was managed with benztropine and lorazepam, and was well tolerated. The patient was discharged to a community inpatient rehabilitation center. Urine drug testing before discharge was negative. This case draws attention to the addictive potential of dimenhydrinate and offers a regime for its medical withdrawal management. Additionally, this case highlights that screening and management of over-the-counter medications warrants further clinical consideration and investigation.
Topics: Benztropine; Bipolar Disorder; Dimenhydrinate; Female; Humans; Infusions, Intravenous; Lorazepam; Middle Aged; Poisoning; Psychotropic Drugs
PubMed: 30844875
DOI: 10.1097/ADM.0000000000000511