piperidines and Dizziness

To develop and compare benefit-risk profiles for rimegepant, ubrogepant, and lasmiditan based on a network meta-analysis (NMA) of published clinical trials.. A fixed-effects Bayesian NMA of randomized controlled trials of lasmiditan, rimegepant, and ubrogepant for the acute treatment of adults with migraine were used to determine risk differences for efficacy and safety outcomes of the 3 treatments compared with pooled placebo. Risk differences were used to calculate number needed to treat (NNT) for pain relief and pain freedom at 2 and 2 to 24 hours and freedom from most bothersome symptoms at 2 hours; and number needed to harm (NNH) for dizziness and nausea, relative to placebo.. Results were based on 5 randomized controlled trials (NCT03461757, NCT02828020, NCT02867709, NCT02439320, and NCT02605174). NNT to achieve sustained pain relief at 2 to 24 hours was lowest for rimegepant 75 mg (5; 95% credible interval [Crl]: 4, 7) and ubrogepant 100 mg (5; 95% Crl: 4, 8) and highest for ubrogepant 25 mg (8; 95% Crl: 5, 16). Rimegepant had the lowest NNT to achieve sustained pain freedom at 2 to 24 hours and lasmiditan 50 mg had the highest (7; 95% Crl: 5, 12 vs. 26; 95% Crl: 13, 95). NNH for dizziness and nausea was highest for ubrogepant 25 mg (28; 95% Crl: 15, 62 and 99; 95% Crl: -2580, 2378, respectively). Lasmiditan 200 mg had the lowest NNH for dizziness and rimegepant 75 mg had the lowest NNH for nausea.. The benefit-risk profiles of lasmiditan, rimegepant, and ubrogepant may improve clinical decision-making.

Topics: Adult; Bayes Theorem; Benzamides; Dizziness; Double-Blind Method; Humans; Migraine Disorders; Nausea; Piperidines; Pyridines; Pyrroles; Serotonin Receptor Agonists; Treatment Outcome

Migraine has been recognized as one of common diseases in the world whose current treatment options are not ideal. Lasmiditan, an oral 5-hydroxytryptamine (HT). PubMed, Cochrane Library, Embase were searched on lasmiditan for the acute treatment of migraine from inception of the databases to Feb 1, 2020. Pain free and pain relief, global impression (very much/much better), and no/mild disability at 2 h in efficacy; total treatment-emergent adverse events (TEAEs), dizziness, nausea, fatigue, paraesthesia and somnolence in safety were extracted from the included studies. A systematic review and meta-analysis was performed using Review Manager Software version 5.3 (RevMan 5.3).. Four RCTs with a total of 4960 subjects met our inclusion criteria. The overall effect estimate showed that lasmiditan was significantly superior to placebo in terms of pain free (RR 1.71, 95% CI 1.55-1.87), pain relief (RR 1.40, 95% CI 1.33-1.47), global impression (very much/much better) (RR 1.55, 95% CI 1.44-1.67), and no/mild disability (RR 1.15, 95% CI 1.10-1.20) at 2 h. For the safety, significant number of patients experienced TEAEs with lasmiditan than with placebo (RR 2.77, 95% CI 2.53-3.03), most TEAEs were central nervous system (CNS)-related and included dizziness (RR 5.81, 95% CI 4.72-7.14), nausea (RR 2.58, 95% CI 1.87-3.57), fatigue (RR 5.38, 95% CI 3.78-7.66), paraesthesia (RR 4.48, 95% CI 3.33-6.02), and somnolence (RR 2.82, 95% CI 2.18-3.66).. This meta-analysis suggests that lasmiditan is effective for the acute treatment of migraine with a higher incidence of CNS-related adverse reactions compared with placebo. Long-term, open-label, multi-dose trials are required to verify the current findings.

Topics: Benzamides; Dizziness; Humans; Migraine Disorders; Nausea; Piperidines; Pyridines; Receptor, Serotonin, 5-HT1F; Receptors, Serotonin; Serotonin Receptor Agonists; Time Factors; Treatment Outcome; Vertigo

Lasmiditan is the first 5-HT. Patients were randomized 1:1:1 to lasmiditan 200 mg lasmiditan 100 mg, or a control group. The incidence of treatment-emergent adverse events (TEAEs), their severity, and incidence by treated attacks for frequently reported TEAEs (≥ 5%) were evaluated. The duration, onset, and relationship of efficacy with very common TEAEs (≥ 10%) was analyzed.. A total of 281 Chinese patients were included in this post hoc analysis. No deaths and no study drug-related treatment emergent serious adverse events (TESAEs) were reported. The incidence of at least one TEAE was higher in patients receiving lasmiditan 200 mg (73.9%) and 100 mg (66.3%) versus placebo (26.6%). TEAEs were generally mild or moderate in severity, and the incidence of frequently reported TEAEs was generally highest during the first attack. Very common TEAEs with lasmiditan included dizziness, asthenia, somnolence, muscular weakness, fatigue, and nausea. The duration of dizziness was longest during the first attack. There were no cardio-cerebrovascular ischemic events and serotonin syndrome. The presence of very common TEAEs (except nausea), and severe dizziness, did not appear to have a negative influence on the efficacy.. In the Chinese population of the CENTURION study, most of the TEAEs were neurologic, of mild or moderate severity, and self-limiting. The distribution of frequently reported TEAEs at the first attack differed from the primary cohort, while the overall safety profile of lasmiditan in the Chinese population was generally consistent with the CENTURION primary cohort. No new safety concerns were observed in the Chinese population.. NCT03670810.. Although there is significant unmet medical need among patients with migraine, there has been no novel compound for treatment of migraine over past two decades in China. These unmet medical needs persist because the current available medications for the acute treatment of migraine are reported to have safety and tolerability issues. Lasmiditan is a new class of acute migraine medication (5-HT receptor agonist with high selectivity for the 5-HT

Topics: Benzamides; Dizziness; Double-Blind Method; Humans; Migraine Disorders; Nausea; Piperidines; Pyridines; Serotonin Receptor Agonists; Treatment Outcome

Determine whether common migraine comorbidities affect the efficacy and safety of lasmiditan, a 5-HT. Across all the Comorbidity Groups, with the potential exception of fatigue, treatment-by-subgroup interaction analyses did not provide evidence of a lasmiditan-driven lasmiditan versus placebo differential treatment effect dependent on Yes versus No comorbidity subgroup for either efficacy or TEAE assessments.. The efficacy and safety of lasmiditan for treatment of individual migraine attacks appear to be independent of comorbid conditions.

Topics: Adult; Benzamides; Comorbidity; Dizziness; Double-Blind Method; Female; Humans; Male; Middle Aged; Migraine without Aura; Nausea; Piperidines; Pyridines; Serotonin Receptor Agonists; Treatment Outcome; Vertigo

SAMURAI and SPARTAN were double-blind, placebo-controlled Phase 3 studies conducted in the United States, as well as the United Kingdom and Germany (SPARTAN only). Individuals with migraine were randomized to receive oral lasmiditan 50 mg (SPARTAN only), 100 mg, 200 mg, or placebo within 4 hours of onset of a migraine attack. The aim of this analysis was to characterize dizziness reported with lasmiditan treatment.. Data from SAMURAI and SPARTAN were pooled for the current post hoc analyses. Onset time and duration of dizziness were analyzed using descriptive statistics. Subgroup analyses based on presence/absence of dizziness were performed for the endpoints of interference with daily activity, patient global impression of change (PGIC), pain at 2 hours, and most bothersome symptom (MBS) at 2 hours based on adverse events occurring within 2 hours of taking study drug.. Dizziness incidence was as follows: Placebo (N = 1262), 2.9% (0.1% severe); lasmiditan 50 mg (N = 654), 8.6% (0.3% severe); lasmiditan 100 mg (N = 1265), 14.9% (0.7% severe); and lasmiditan 200 mg (N = 1258), 16.8% (1.4% severe). Among participants who received lasmiditan as their first dose, risk factors for dizziness were higher lasmiditan dosage, being non-Hispanic/Latino, mild or moderate severity of migraine attack, and lower body mass index. The median time to onset of dizziness was generally 30-40 minutes, and the median duration was 1.5-2 hours. The presence of dizziness did not appear to have a negative influence on lasmiditan's effect on daily activity, PGIC, freedom from pain, or MBS. Overall, 21 participants experienced vertigo: Lasmiditan 50 mg, n = 2 (0.3%); 100 mg, n = 11 (0.9%); 200 mg, n = 7 (0.6%); and placebo, n = 1 (<0.1%).. The incidence of dizziness with lasmiditan increased with dose. Dizziness was generally mild or moderate in severity and of quick onset and short duration. The presence of dizziness did not influence drug efficacy.

Topics: Acute Disease; Adult; Benzamides; Dizziness; Double-Blind Method; Female; Humans; Male; Middle Aged; Migraine Disorders; Outcome Assessment, Health Care; Piperidines; Pyridines; Severity of Illness Index; Vertigo

Bilastine is a highly selective, non-sedating antihistamine, indicated for the symptomatic treatment of allergic rhinoconjunctivitis and urticaria. Available data suggest that bilastine interferes neither with driving ability nor with flying-related performance. However, no data are available on the effect of bilastine on the driving ability in extreme conditions. Here we analyzed the effect of 7 days treatment with 20 mg bilastine in patients with allergic rhinitis and/or chronic urticaria, on psychophysical performance assessed by the Formula One (F1) high-speed simulator-driving test.. This study is a phase IV, interventional, prospective, mono-centric, single arm, open-label trial. Eighteen outpatients affected by allergic rhinitis and/or chronic urticaria, able to perform a preliminary driving test on F1 simulator were considered (V-1). First, the patients had a screening visit to assess their eligibility (V0). Visit 1 (V1), at the end of placebo before bilastine treatment and Visit 2 (V2), at the end of bilastine treatment. The primary variable parameter was the ability to maintain the vehicle in a central position at different speeds (50, 150, and 250 km/h).. Bilastine had a good safety profile and was well tolerated in terms of adverse events, laboratory parameters and vital signs. Bilastine did not have any negative effect on the ability to maintain the requested path, a constant speed as well as on attention and reactivity levels, even in extreme driving conditions.. This study is the first done in patients with allergic rhinitis and/or chronic urticaria using a F1-high speed simulator-driving test evaluating subjects' performance under bilastine treatment.

Topics: Adult; Attention; Automobile Driving; Benzimidazoles; Chronic Disease; Computer Simulation; Dizziness; Female; Histamine Antagonists; Histamine H1 Antagonists, Non-Sedating; Humans; Male; Middle Aged; Piperidines; Prospective Studies; Rhinitis, Allergic; Urticaria; Young Adult

While community distribution of topical repellents has been proposed as an additional malaria control intervention, the safety of this intervention at the population level remains poorly evaluated. We describe the safety of mass distribution of the picaridin repellent during a cluster-randomised trial in rural Cambodia in 2012-2013.. The repellent was distributed among 57 intervention villages with around 25,000 inhabitants by a team of village distributors. Information on individual adverse events, reported by phone by the village distributors, was obtained through home visits. Information on perceived side effects, reported at the family level, was obtained during two-weekly bottle exchange. Adverse events were classified as adverse reactions (events likely linked to the repellent), cases of repellent abuse and events not related to the repellent use, and classified as per Common Terminology Criteria for Adverse Events.. Of the 41 adverse events notified by phone by the village distributors, there were 22 adverse reactions, 11 cases of repellent abuse (6 accidental, 5 suicide attempts) and 8 non-related events. All adverse reactions were mild, occurred in the first few months of use, and mainly manifested as skin conditions. Of the 11 cases of abuse, 2 were moderate and 2 life-threatening. All cases with adverse reactions and repellent abuse recovered completely. 20% of families reported perceived side effects, mainly itching, headache, dizziness and bad smell, but few discontinued repellent use.. Adverse reactions and abuse during mass use of picaridin were uncommon and generally mild, supporting the safety of the picaridin repellent for malaria control.

Topics: Cambodia; Dizziness; Headache; Humans; Insect Repellents; Mosquito Control; Piperidines; Rural Population; Treatment Outcome

Sustained-release, high-dose (23 mg/d) donepezil has been approved for treatment of moderate to severe Alzheimer disease (AD). Based on a previous clinical trial, body weight of less than 55 kg is a risk factor for adverse events with donepezil 23 mg/d treatment in global population.. To clarify whether this finding is consistent across ethnic groups that vary in absolute body mass, we recruited Korean patients aged 45 to 90 years with moderate to severe AD who had been receiving standard donepezil immediate release 10 mg/d for at least 3 months. After screening, we analyzed a final cohort of 166 patients who received donepezil 23 mg/d for 24 weeks to compare the occurrence of treatment-emergent adverse events (TEAEs) between patients with high versus low body mass index (BMI) based on the World Health Organization overweight criteria for Asian populations (23 kg/m).. Treatment-emergent adverse events were reported by 79.45% of patients in the lower BMI group and 58.06% of patients in the higher BMI group (odds ratio, 2.79; 95% confidence interval, 1.39-5.63; χ = 7.58, P = 0.006). In a multivariable survival analysis, the group with lower BMI showed a higher occurrence of TEAEs (hazard ratio, 1.83; 95% confidence interval, 1.25-2.68; P = 0.002).. In Korean patients with moderate to severe AD receiving high-dose donepezil over 24 weeks, TEAEs were significantly more common in those with lower BMI (not clinically overweight), especially nausea. This finding may inform clinical practice for Asian patients.

Topics: Administration, Oral; Aged; Aged, 80 and over; Alzheimer Disease; Body Mass Index; Body Weight; Cholinesterase Inhibitors; Delayed-Action Preparations; Dizziness; Donepezil; Female; Humans; Indans; Male; Middle Aged; Nausea; Piperidines; Prospective Studies; Republic of Korea

To describe secondary analyses from a 12-week, randomized, open-label trial where adult schizophrenia outpatients receiving risperidone, olanzapine, or aripiprazole were switched to iloperidone.. Patients were randomized into two groups: one where the antecedent antipsychotic dose was titrated downwards to zero over 2 weeks (n=240), and the other group where the antecedent antipsychotic was abruptly stopped (n=260). Adaptations of the Clinical Global Impression scale were used to evaluate clinical changes. Other assessments included the reporting of adverse events (AEs), study discontinuation, body weight, and metabolic variables.. Improvement was steady throughout the study for both gradual- and immediate-switch groups starting at Week 1 and continuing through Week 12. Discontinuations due to AEs in the first 2 weeks of treatment were higher for the immediate-switch group compared with the gradual-switch group (10.8% vs. 5.4%, NNT 19, 95% CI 10-151). Fewer patients in the gradual-switch group experienced dizziness as an AE, whereas a higher percentage of patients in the immediate-switch group exhibited earlier onset of a therapeutic response within the first 2 weeks; both groups were comparable thereafter with low rates of dizziness and similar efficacy outcomes.. Switching to iloperidone can be accomplished either with a gradual crossover or immediate discontinuation of the prior antipsychotic; however, the immediate-switch method is associated with greater proportion of initial dizziness. The observed outcomes are consistent with what has been previously reported regarding iloperidone's favorable akathisia/EPS profile and modest impact on somnolence/sedation, body weight, and metabolic variables.

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dizziness; Female; Humans; Isoxazoles; Male; Olanzapine; Piperazines; Piperidines; Quinolones; Risperidone; Schizophrenia; Treatment Outcome

Breech presentation occurs in up to 3% of pregnancies at term and may be an indication for caesarean delivery. External cephalic version can be effective in repositioning the fetus in a cephalic presentation, but may be painful for the mother. Our aim was to assess the efficacy of remifentanil versus placebo for pain relief during external cephalic version.. A randomized, double-blind, controlled trial that included women at 36-41 weeks of gestation with non-cephalic presentations was performed. Women were randomized to receive either a remifentanil infusion at 0.1 μg/kg/min and demand boluses of 0.1 μg/kg, or saline placebo. The primary outcome was the numerical rating pain score (0-10) after external cephalic version.. Sixty women were recruited, 29 in the control group and 31 in the remifentanil group. There were significant differences in pain scores at the end of the procedure (control 6.5 ± 2.4 vs. remifentanil 4.7 ± 2.5, P = 0.005) but not 10 min later (P = 0.054). The overall success rate for external cephalic version was 49% with no significant differences between groups (remifentanil group 54.8% vs. control group 41.3%, P = 0.358). In the remifentanil group, there was one case of nausea and vomiting, one of drowsiness and three cases of fetal bradycardia. In the control group, there were three cases of nausea and vomiting, one of dizziness and nine cases of fetal bradycardia.. Intravenous remifentanil with bolus doses on demand during external cephalic version achieved a reduction in pain and increased maternal satisfaction. There were no additional adverse effects, and no difference in the success rate of external cephalic version or the incidence of fetal bradycardia.

Topics: Adult; Analgesia; Analgesics, Opioid; Bradycardia; Breech Presentation; Dizziness; Double-Blind Method; Female; Fetal Diseases; Humans; Nausea; Pain; Pain Management; Patient Satisfaction; Piperidines; Placebos; Pregnancy; Remifentanil; Treatment Outcome; Version, Fetal; Vomiting

To assess the 1-year safety profile of the dopaminergic stabilizer pridopidine in patients with Huntington disease.. Patients received pridopidine 45 mg/day for 4 weeks then pridopidine 90 mg/day for 22 weeks in this 6-month open-label extension (OLE) of the 6-month MermaiHD randomized controlled trial (RCT). Any adverse events (AEs) were recorded. Patients were categorized by their RCT treatment group (placebo, pridopidine 45 mg/day, pridopidine 90 mg/day).. Of the 386 patients who completed the RCT, 353 entered the OLE and 305 (86.4%) completed. In 1 year, similar percentages of patients from each group reported ≥1 AE (placebo, 79.6% [n = 90/113]; 45 mg/day, 80.8% [n = 101/125]; 90 mg/day, 82.6% [n = 95/115]) and ≥1 serious AE (8.0% [n = 9/113], 12.8% [n = 16/125], and 8.7% [n = 10/115], respectively). The AE profile across both studies was similar; falls and worsening of chorea were most commonly reported. During the OLE, more patients previously receiving pridopidine reported ≥1 AE (67.9% [n = 163/240]) than those who had received placebo (56.6% [n = 64/113]). Early in the RCT, small increases in heart rate were reported in patients receiving pridopidine. During 1 year, no clinically meaningful changes in laboratory parameters or EKG-related safety concerns were identified.. Pridopidine (≤90 mg/day) has an acceptable safety profile and is well-tolerated for 1 year.. This study provides Class IV evidence that pridopidine (≤90 mg/day) is generally safe and well-tolerated in patients with Huntington disease for up to 1 year.

Topics: Adult; Depression; Dizziness; Female; Humans; Huntington Disease; Male; Middle Aged; Piperidines; Time Factors; Treatment Outcome

To prospectively evaluate the efficacy and safety of alogliptin versus glipizide in elderly patients with type 2 diabetes mellitus (T2DM) over 1 year of treatment.. This was a randomized, double-blind, active-controlled study of elderly T2DM patients (aged 65-90 years) with mild hyperglycaemia on diet/exercise therapy alone [glycosylated haemoglobin (HbA1c) 6.5-9.0%] or plus oral antidiabetic monotherapy (HbA1c 6.5-8.0%). Patients were randomized to once-daily alogliptin 25 mg or glipizide 5 mg titrated to 10 mg, if needed. Hypoglycaemic episodes were systematically captured under predefined criteria.. In the primary analysis, HbA1c mean changes from a baseline of 7.5% were -0.14% with alogliptin (n = 222) and -0.09% with glipizide (n = 219) at the end of the study, demonstrating non-inferiority of alogliptin to glipizide [least squares (LS) mean difference = -0.05%; one-sided 97.5% confidence interval (CI): -∞, 0.13%]. More clinically relevant HbA1c reductions occurred among patients who completed the study: -0.42 and -0.33% with alogliptin and glipizide, with non-inferiority again confirmed (LS mean difference = -0.09%; one-sided 97.5% CI: -∞, 0.07%). Overall, alogliptin was safe and well tolerated, with notably fewer hypoglycaemic episodes than glipizide [5.4% (31 episodes) vs. 26.0% (232 episodes), respectively]; three patients experienced severe hypoglycaemia, all with glipizide. Alogliptin also resulted in favourable weight changes versus glipizide (-0.62 vs. 0.60 kg at week 52; p < 0.001).. Alogliptin monotherapy maintained glycaemic control comparable to that of glipizide in elderly patients with T2DM over 1 year of treatment, with substantially lower risk of hypoglycaemia and without weight gain.

Topics: Aged; Aged, 80 and over; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dizziness; Double-Blind Method; Female; Glipizide; Glycated Hemoglobin; Headache; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Male; Metformin; Piperidines; Prospective Studies; Treatment Outcome; Triglycerides; Uracil; Weight Gain

Performance of middle-ear surgery under local anaesthesia has several advantages, but many patients complain of pain, anxiety and adverse events (e.g. dizziness and nausea). To minimise such problems, we compared sedation with midazolam alone versus midazolam with remifentanil.. We initially observed 19 patients undergoing middle-ear surgery under local anaesthesia, as controls. We then sedated a further 40 patients undergoing such surgery, with either midazolam or midazolam plus remifentanil.. The sedated patients had significantly lower incidences of local anaesthesia injection pain (p < 0.001), intra-operative pain (p < 0.001), intra-operative anxiety (p < 0.001) and adverse events, compared with the control group. Patients sedated with midazolam plus remifentanil reported less intra-operative anxiety (p = 0.010) and greater post-operative satisfaction with sedation (p = 0.007), compared with those sedated with midazolam only.. Patients undergoing middle-ear surgery under local anaesthesia alone frequently report pain, anxiety and adverse events. However, the majority of our patients who were sedated with midazolam satisfactorily overcame pain, anxiety and adverse events. Results were better still when midazolam was accompanied by remifentanil.

Topics: Adult; Anesthetics, Local; Anxiety; Conscious Sedation; Dizziness; Drug Therapy, Combination; Ear, Middle; Female; Humans; Hypnotics and Sedatives; Infusions, Intravenous; Injections, Intradermal; Intraoperative Complications; Male; Midazolam; Middle Aged; Otologic Surgical Procedures; Pain; Patient Satisfaction; Piperidines; Postoperative Nausea and Vomiting; Remifentanil

Early recovery of patients following sedation/analgesia and anesthesia is important in ambulatory practice. The aim of this study was to assess whether modafinil, used for the treatment of narcolepsy, improves recovery following sedation/analgesia.. Patients scheduled for extracorporeal shock wave lithotripsy were randomly assigned to one of four groups. Two groups received a combination of fentanyl/midazolam with either modafinil or placebo. The remaining groups received remifentanil/propofol with either modafinil or placebo. Modafinil 200 mg was administered to the treatment group patients 1 h before sedation/analgesia. Groups were compared using the digital symbol substitution test (DSST), trail making test (TMT), observer scale of sedation and analgesia (OAA/S) and Aldrete score. Verbal rating scale (VRS) scores for secondary outcome variables e.g. energy, tiredness and dizziness were also recorded before and after treatment.. Sixty-seven patients successfully completed the study. Groups received similar doses of sedation and analgesic drugs. No statistically significant difference was found for DSST between groups. No significant adverse effects occurred in relation to modafinil. No statistically significant difference between groups was identified for TMT, OAA/S and Aldrete scores. The mean VRS score for tiredness was lesser in the modafinil/fentanyl/midazolam group [1.3 (2.0)] compared with the placebo group [3.8 (2.5)], P=0.02. Such a difference was not found between the remifentanil/propofol groups [placebo 2.6 (2.2) vs. modafinil 3.1(2.7)], p>0.05. Dizziness was greater in the modafinil/remifentanil/propofol group 1.7 (2.0) vs. placebo 0.0 (0.5), p<0.05.. Modafinil reduces patient-reported tiredness after sedation/analgesia but does not improve recovery in terms of objective measures of patient psychomotor skills.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesia; Anesthesia Recovery Period; Anesthetics, Inhalation; Appetite; Benzhydryl Compounds; Central Nervous System Stimulants; Deep Sedation; Dizziness; Fatigue; Fentanyl; Humans; Lithotripsy; Midazolam; Middle Aged; Modafinil; Nausea; Neuropsychological Tests; Pain; Piperidines; Placebos; Propofol; Psychomotor Agitation; Psychomotor Performance; Relaxation; Remifentanil; Sleep Stages; Young Adult

In recent years, there has been an increased interest in using a multimodal approach with combined agents to treat postoperative nausea and vomiting. This study evaluated whether the addition of an oral dose of the neurokinin-1 receptor antagonist casopitant improved the antiemetic efficacy of an intravenous dose of ondansetron hydrochloride.. The authors enrolled 702 premenopausal or perimenopausal, nonsmoking, female patients aged 18-55 yr with a history of postoperative nausea and vomiting and/or motion sickness undergoing a laparoscopic or laparotomic gynecologic surgical procedure or laparoscopic cholecystectomy with general anesthesia. Subjects were randomized to one of five treatment arms: standard ondansetron 4 mg with casopitant at 0, 50, 100, or 150 mg, or 0 mg ondansetron with casopitant at 150 mg (the latter arm was considered an exploratory study group and was included in the safety analysis but not in the efficacy analysis).. A significantly greater proportion of patients in all of the active casopitant plus ondansetron groups achieved a complete response (i.e., no vomiting, retching, rescue medication, or premature withdrawal) during the first 24 h postoperatively versus those in the ondansetron-alone group (59-62% vs. 40%, respectively; P = 0.0006). All active doses seemed to be well tolerated; headache, dizziness, and constipation were the most frequently reported adverse events.. Compared with ondansetron alone, the casopitant and ondansetron combination results in superior emesis prevention during the first 24 h postoperatively in female patients with known risk factors for postoperative nausea and vomiting.

Topics: Administration, Oral; Adolescent; Adult; Anesthesia, General; Antiemetics; Cholecystectomy, Laparoscopic; Constipation; Dizziness; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Gynecologic Surgical Procedures; Headache; Humans; Middle Aged; Neurokinin-1 Receptor Antagonists; Ondansetron; Piperazines; Piperidines; Postoperative Nausea and Vomiting; Risk Factors; Treatment Outcome; Young Adult

Gabapentin is an anticonvulsant drug that has analgesic properties for acute postoperative pain. However, the analgesic effect of gabapentin as an antiepileptic prophylactic drug on patients undergoing craniotomy is unclear. In this study, we evaluated the postoperative effectiveness of gabapentin on acute postoperative pain when it is used for antiepileptic prophylaxis in patients undergoing craniotomy for supratentorial tumor resection.. Eighty patients undergoing craniotomy for supratentorial tumor resection were randomly assigned into two groups. Patients in Group G (n = 40) received oral gabapentin (3 x 400 mg), and patients in Group P (n = 40) received oral phenytoin (3 x 100 mg) for 7 days before the operation and postoperatively. An identical anesthesia protocol was performed for both the groups. Anesthesia was maintained with propofol and remifentanil infusion. Patient-controlled analgesia with morphine was used, and pain levels were measured. The antiepileptic-related side effects, anesthetic consumption, duration of anesthesia and surgery, tracheal extubation time, postoperative pain scores, morphine consumption, and sedation scores were recorded.. Thirty-seven patients in Group G and 38 patients in Group P completed the study. During the preoperative period in Group G, one patient had severe fatigue, one had severe dizziness, and one patient's surgical procedure was changed. The median plasma levels of gabapentin were 34 micromol/mL (range, 23-51 micromol/mL) in 34 patients. In Group P, one patient withdrew from the study preoperatively and one developed transient neurological symptoms postoperatively. The demographic data and mean duration of anesthesia and surgery were similar in both the groups. The total propofol and remifentanil consumption in Group G (1847 +/- 548 mg/3034 +/- 1334 microg) was significantly less than that of Group P (2293 +/- 580 mg/4287 +/- 1282 microg) (P = 0.01). However, tracheal extubation could be done earlier in Group P (4.5 +/- 2 min) than in Group G (16.6 +/- 22 min) (P < 0.001). Pain scores were significantly higher in Group P at 15 min, 30 min, and 1 h (P < 0.001). The total morphine consumption was also significantly higher in Group P (33 +/- 17 mg vs 24 +/- 19 mg) (P = 0.01). The postoperative sedation scores were significantly higher in Group G at 15 min, 30 min, 1 h, and 2 h (P < 0.001).. The administration of gabapentin to patients undergoing craniotomy for supratentorial tumor resection was effective for acute postoperative pain. It also decreased analgesic consumption after surgery. However, it may lead to side effects such as delayed tracheal extubation and increased sedation postoperatively.

Topics: Administration, Oral; Adult; Amines; Analgesia, Patient-Controlled; Analgesics; Analgesics, Opioid; Anesthetics, Intravenous; Anticonvulsants; Craniotomy; Cyclohexanecarboxylic Acids; Dizziness; Drug Administration Schedule; Fatigue; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Intubation, Intratracheal; Male; Middle Aged; Morphine; Pain Measurement; Pain, Postoperative; Phenytoin; Piperidines; Preanesthetic Medication; Propofol; Prospective Studies; Remifentanil; Sleep; Supratentorial Neoplasms; Time Factors; Treatment Outcome

This randomized, double-blind study was designed to evaluate analgesic effectiveness and side effects of two remifentanil infusion rates in patients undergoing extracorporeal shock wave lithotripsy (ESWL) for renal stones. We included 200 patients who were administered remifentanil either 0.05 microg x kg(-1) x min(-1) (n = 100) or 0.1 microg x kg(-1) x min(-1) (n = 100) plus demand bolus of 10 microg of remifentanil via a patient-controlled analgesia (PCA) device. No other sedating drugs were given. The frequencies of PCA demands and deliveries were recorded. Arterial blood pressure, oxygen saturation, and respiratory rate were recorded throughout the procedure; postoperative nausea and vomiting (PONV), dizziness, itching, agitation, and respiratory depression were measured posttreatment. Visual analog scale (VAS) scores were taken preoperatively, directly postoperatively, and 30 min after finishing the procedure. There were no statistically significant differences in the frequency of PCA demands and delivered boluses or among perioperative VAS scores. The extent of PONV and frequency of dizziness and itching immediately after and dizziness 30 min after the end of treatment were significantly reduced in the smaller dose group. We conclude that a remifentanil regimen of 0.05 microg x kg(-1) x min(-1) plus 10 microg demands is superior to 0.1 microg x kg(-1) x min(-1) plus demands, as there was no difference in the VAS scores recorded between groups and it has a less frequent incidence of side effects in patients receiving ESWL.. Remifentanil is an appropriate analgesic choice for patients undergoing extracorporeal shock wave lithotripsy (ESWL) therapy, as it has both fast onset and offset times. We studied remifentanil as a sole drug for ESWL and have shown that an infusion rate of 0.05 microg x kg-1 x min-1 plus patient-controlled analgesia demands of 10 microg provides adequate analgesia and has significantly less side effects than a dose of 0.1 microg x kg-1 x min-1 plus 10 microg demands.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Analgesia, Patient-Controlled; Analgesics, Opioid; Dizziness; Dose-Response Relationship, Drug; Female; Humans; Infusions, Intravenous; Kidney Calculi; Lithotripsy; Male; Middle Aged; Pain Measurement; Piperidines; Postoperative Complications; Postoperative Nausea and Vomiting; Pruritus; Remifentanil; Single-Blind Method

Stapedotomy for otosclerosis presents particular anaesthesiology demands as the surgeon has to assess functional results during the operation, work with some bleeding, be ensured the collaboration of the patient, and limit the occurrence of intra- and post-operative symptoms (dizziness, nausea, vomiting and pain). Remifentanyl, a micro-opioid selective agonist characterised by short latency and duration, has been used for about 2 years at the Otolaryngological Unit of the "Federico II" University of Naples for patients with otosclerosis undergoing stapedotomy. Aim of the study was, therefore, to assess: efficacy and tolerability of Remifentanyl in combination with a local anaesthetic in surgical procedures for otosclerosis; intra- and post-operative reduction in patient symptoms of dizziness, nausea, vomiting and pain; reduction of intra-operative bleeding; degree of patient collaboration and optimisation of anaesthesiological and vital parameters monitored during surgery. The study was carried out on 92 patients with otosclerosis, (17 M, 75 F), median age 41 years (range 25-56), undergoing stapedotomy. Patients were randomly assigned to one of two groups, which were homogeneous as far as concerns age, sex and pre-operative hearing: i. Group A (50 patients), received Remifentanyl infusion in combination with canal injection for local anaesthesia with Mepivacaine 2% and Adrenalin 1/100,000; ii. Group B (42 patients), received only local anaesthetic by infiltration of the external canal ear. Remifentanyl led to an improvement over the local anaesthetic technique previously used, with a clear decrease in intra- and post-operative neurovegetative symptoms such as dizziness, nausea, vomiting and pain, as well as reduced bleeding.

Topics: Adult; Analgesics, Opioid; Dizziness; Female; Humans; Hypnotics and Sedatives; Intraoperative Complications; Male; Middle Aged; Nausea; Otosclerosis; Pain; Piperidines; Postoperative Complications; Remifentanil; Stapes Surgery; Vomiting

Donepezil is an acetylcholinesterase inhibitor marketed for treatment of memory loss and behavioral deterioration associated with the acetylcholine deficit of Alzheimer's disease. We investigated the utility and tolerability of donepezil in nongeriatric affective illness for treatment of psychotropic-induced memory loss, dry mouth, and constipation.. Nondemented outpatients with stabilized DSM-IV affective illness took 5 mg/day of donepezil for 3 weeks and then increased to 10 mg/day in open trials. Self-rating scales of target symptoms were completed by patients before and 3 to 4 weeks after starting each dose condition. Patients who chose to continue donepezil therapy returned for clinical monitoring every 4 to 8 weeks.. Eleven women and 11 men (mean +/- SD age = 45.4+/-8.5 years) completed donepezil trials. Nineteen patients with memory loss rated improvement while taking 5 mg/day of donepezil (p<.001); subsequently, 6 rated further improvement with 10 mg/day (p = .057). Donepezil, 5 mg/day, also reduced ratings of dry mouth (N = 16; p<.001) and constipation (N = 11; p<.05). Side effects included insomnia, nausea, vomiting, and diarrhea; surprisingly, 2 bipolar patients became manic within hours of starting donepezil. Sixteen patients (72%) continued donepezil for an average of 7 months. Consideration of family histories suggested that donepezil response in affective illness may be an early indicator of vulnerability to dementia of the Alzheimer's type.. (1) Donepezil can reduce memory loss, dry mouth, and constipation in nongeriatric affective patients, but may trigger mania; and (2) long-term follow-up will reveal the predictive value for dementia of donepezil's memory restoration in nongeriatric subjects.

Topics: Adult; Ambulatory Care; Cholinesterase Inhibitors; Constipation; Depressive Disorder; Diarrhea; Dizziness; Donepezil; Drug Administration Schedule; Female; Humans; Indans; Male; Memory Disorders; Middle Aged; Piperidines; Psychotropic Drugs; Sleep Initiation and Maintenance Disorders; Xerostomia

Given increased knowledge from molecular biology and pharmacology, it is apparent that multiple factors can interact to produce clinically meaningful differences in a drug's effect in specific individuals (i.e., personalized medicine). This topic is discussed in this column using iloperidone as an example. The variables discussed include dose, dosing schedule, genes, drug-drug interactions, and other medical factors. How such variables can combine to alter a drug's effect is illustrated with a case example and the results of a thorough QTc study of iloperidone.

Topics: Affective Disorders, Psychotic; Aged; Antipsychotic Agents; Depressive Disorder, Major; Dizziness; Drug Interactions; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels; Humans; Isoxazoles; Male; Paroxetine; Pharmacogenetics; Piperidines; Precision Medicine

Flecainide, a new antiarrhythmic agent, was given to eight healthy men to ascertain plasma drug levels and to assess tolerance for the drug. Each subject received a single intravenous (IV) dose (0.5, 1, 1.5, or 2 mg/kg) of flecainide, and plasma levels of unchanged flecainide were measured by gas-liquid chromatography. After an initial rapid distribution phase, the drug's plasma half-life (terminal elimination phase) ranged from seven to 15 hours (mean, 11 hours); half-life was apparently independent of dose level. Immediately after IV administration, the relatively high plasma drug levels seen during the short distribution phase were associated with minor and transient side effects in some subjects receiving the two higher doses; overall, the drug was well tolerated. Plasma flecainide levels 60 minutes after administration (after distribution) ranged from 52 to 300 ng/ml and were reasonably proportional to dose level. The drug's relatively long plasma half-life in humans indicates that plasma levels will be maintained for prolonged periods; thus flecainide should provide sustained therapeutic activity in patients with cardiac arrhythmias.

Topics: Adult; Anti-Arrhythmia Agents; Chromatography, Gas; Dizziness; Drug Tolerance; Electrocardiography; Flecainide; Half-Life; Humans; Male; Piperidines; Vision, Ocular; Xerostomia

During a one-week short-term in-hospital period, 60 patients with chronic ventricular arrhythmias were treated with 200 mg flecainide twice a day. Flecainide reduced premature ventricular complexes (PVCs) by more than 85% without causing important side-effects in 47 patients, who entered a one-year follow-up period and were followed with bimonthly 24-h ECGs. Median PVC-frequency remained reduced by more than 99% during the follow-up period. Repetitive ventricular beats and ventricular tachycardia were present in 83% and 42% of patients, respectively, before flecainide. During follow-up, these arrhythmias were seen in less than 32% and less than 10% of patients, respectively, at each 24-h ECG. Furthermore, the mean number of hours with repetitive ventricular beats and ventricular tachycardia remained reduced by more than 76% and more than 79%, respectively, throughout the follow-up period. Ventricular arrhythmias remained suppressed despite a gradual reduction in flecainide dosages (to a median of 300 mg day-1) and flecainide plasma levels. In nine out of 47 patients, an increase in ventricular arrhythmias above baseline values on one or more occasions was observed. During a flecainide withdrawal period, a 65-fold increase in median PVC-frequency was observed and ventricular tachycardia reappeared in 18 patients. Subjective side-effects were acceptable except for two patients. During the follow-up period, one patient developed reversible heart failure and sinus node dysfunction. During the total study period, four patients, with either severe coronary artery disease (2) or cardiomyopathy (2) developed lethal arrhythmias (3) or ischaemic events (1). We conclude that prolonged flecainide treatment is effective in a high proportion of patients with chronic ventricular arrhythmias. In some patients an arrhythmogenic effect may occur.

Topics: Adult; Aged; Arrhythmias, Cardiac; Chronic Disease; Dizziness; Drug Evaluation; Electrocardiography; Female; Flecainide; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Piperidines; Time Factors

The results of a well-controlled multicenter shortterm safety and efficacy study, supported by results from several long-term studies, indicate that therapeutic doses of flecainide are well tolerated by most patients. The most frequently reported extracardiac adverse experiences were dizziness (30%) and visual disturbances (28%), often occurring in tandem. Headache, nausea, dyspnea and chest pain occurred at incidences of 6 to 9%; other adverse experiences occurred at incidences of greater than or equal to 5%. Because of study design, it is likely that these figures are overestimates; they include all reports, whether or not they were caused by flecainide. Extracardiac adverse experiences were given as reasons contributing to discontinuation of therapy in 10% of patients in the short-term and 6% of patients in the long-term studies. In most cases the inability to tolerate flecainide became evident early in therapy. No new adverse experiences indicative of any chronic toxic effect of flecainide were reported during the long-term studies. Side effects tended to be intermittent and to decrease over time.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Dizziness; Dyspnea; Flecainide; Headache; Humans; Nausea; Piperidines; Vision Disorders

Topics: Dizziness; Humans; Ketotifen; Piperidines; Sleep Stages; Thiophenes