A Pilot Study Assessing Common Medication Organizers for Child-Resistant Features.

Introduction: Prescription and most over-the-counter medicines are required to have child-resistant packaging and/or labeled with instructions "Keep out of reach of children." Although medication organizers are not required to have such design features or instructions, these could help prevent unsupervised ingestions by children. Commonly purchased medication organizers were evaluated for child-resistant design features and instructions for safe use to prevent unsupervised ingestions. Methods: The 29 best-selling medication organizers on Amazon.com were identified, and product identifiers, design characteristics, and safety characteristics were recorded using a standardized instrument. Results: Of the 29 medication organizers, none claimed to be child resistant. Only 31% provided a specific warning that the organizer was not child resistant on the packaging; only 41% communicated "Keep out of reach of children." Most organizers (59%) provided neither a warning that the organizer was not child resistant nor instructions to store out of reach of children. The majority of organizers (79%) shared the following characteristics: plastic construction, rectangular shape, nonelectronic flip-top opening mechanisms, and 7-day usage. Conclusions: Opportunities exist for manufacturers of medication organizers to improve child-resistant product design, provide information to help prevent unsupervised ingestions (directions to keep the device out of the reach of children), and help to reduce unsupervised ingestions.

Sleep improvements following atopic dermatitis management in young children.

OBJECTIVES: The purpose of this pilot study was to assess improvements in associated sleep and caregiver mood following treatment of atopic dermatitis in young children. METHODS: Participants included children (n = 23; Mage = 22.0 months) and their caregivers. Topical management of atopic dermatitis was conducted for 2 weeks, with measures of skin, sleep (child, caregiver), and mood (caregiver) at baseline and day 14. RESULTS: Topical management resulted in significant improvements in child skin, with associated increases in sleep consolidation. There were similar improvements in caregiver nightwakings, with nighttime sleep duration improving by over an hour. Caregivers also reported more energy to engage with their family and feeling better rested. CONCLUSIONS: Overall, topical management significantly improved atopic dermatitis. There were concomitant improvements in sleep outcomes for children and their caregivers, as well as caregiver mood. Daily management of atopic dermatitis may result in improvements in not just skin health but also sleep and family well-being.

Results from a prospective observational study of men with premature ejaculation treated with dapoxetine or alternative care: the PAUSE study.

BACKGROUND: Dapoxetine hydrochloride is a selective serotonin reuptake inhibitor and the first drug approved for the on-demand treatment of premature ejaculation (PE). Its safety was established in a thorough clinical development program. OBJECTIVE: To characterize the safety profile of dapoxetine in PE treatment and to report the incidence, severity, and type of adverse events. DESIGN, SETTING, AND PARTICIPANTS: We conducted a 12-wk, open-label, observational study with a 4-wk, postobservational contact. A total of 10,028 patients were enrolled, with 6712 patients (67.6%) treated with dapoxetine 30-60 mg (group A) and 3316 (32.4%) treated with alternative care/nondapoxetine (group B). INTERVENTIONS: Treatment with dapoxetine or alternative care/nondapoxetine. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Treatment-emergent adverse events (TEAEs) and concomitant therapy use during the 12-wk observational and the postobservational period were reported. RESULTS AND LIMITATIONS: The mean age for all patients was 40.5 yr. In group A, 93.0% of the patients were initially prescribed dapoxetine 30 mg. Treatment options for group B patients included clomipramine, paroxetine, fluoxetine, sertraline, topical drugs, condoms, and behavioral counseling. Both treatment regimens were well tolerated. TEAEs were reported by 12.0% and 8.9% of group A and group B, respectively, with the highest incidence observed in patients aged >65 yr for group A (21.4%) and 30-39 yr (9.8%) for group B. The most commonly reported TEAEs were nausea, headache, and vertigo, with a higher incidence in group A (3.1%, 2.6%, and 1.0%, respectively) than in group B (oral drugs: 2.3%, 1.3%, and 0.9%, respectively). There were no cases of syncope in group A and one case in group B. A major limitation is that this was a nonrandomized, open-label, short-term study lacking efficacy data. CONCLUSIONS: The results of this postmarketing observational study demonstrated that dapoxetine for treatment of PE has a good safety profile and low prevalence of TEAEs. Syncope and major cardiovascular adverse events were not reported. The high level of adherence by healthcare providers to the contraindications, special warnings, and precautions for dapoxetine minimizes the risk for its use in routine clinical practice. The current risk minimization measures for its identified and potential risks are effective.

Efficacy and safety of dapoxetine in men with premature ejaculation and concomitant erectile dysfunction treated with a phosphodiesterase type 5 inhibitor: randomized, placebo-controlled, phase III study.

INTRODUCTION: Men with comorbid erectile dysfunction (ED) and premature ejaculation (PE) may be concomitantly prescribed a phosphodiesterase type 5 (PDE5) inhibitor and dapoxetine. AIM: Evaluate efficacy and safety of dapoxetine 30 mg and 60 mg on demand (prn) in men with PE and ED who were being treated with PDE5 inhibitors. METHODS: This randomized, double-blind, placebo-controlled, flexible-dose, multicenter study enrolled men ≥18 years who met diagnostic criteria for PE including intravaginal ejaculatory latency time (IELT) of ≤2 minutes in ≥75% of sexual intercourse episodes; were on stable regimen of a PDE5 inhibitor; and had International Index of Erectile Function-erectile function domain score ≥21. Subjects received placebo, dapoxetine 30 mg, or dapoxetine 60 mg prn (1-3 hours before intercourse) for 12 weeks. MAIN OUTCOME MEASURE: Stopwatch-measured average IELT, Clinical Global Impression of Change (CGIC) in PE, Premature Ejaculation Profile (PEP), and treatment-emergent adverse events (TEAEs). RESULTS: Of 495 subjects randomized, 429 completed the study. Arithmetic mean average IELT significantly increased with dapoxetine vs. placebo at end point (5.2 vs. 3.4 minutes) and weeks 4, 8, and 12 (P ≤ 0.002 for all). Men who described their PE at least "better" using the CGIC were significantly greater with dapoxetine vs. placebo at end point (56.5% vs. 35.4%) and weeks 4, 8, and 12 (P ≤ 0.001 for all). Significantly better outcomes were also reported with dapoxetine vs. placebo on PEP measures. Incidence of TEAEs was 20.0% and 29.6% in placebo- and dapoxetine-treated subjects, respectively (P = 0.0135). TEAEs led to discontinuation in 1.6% of subjects in both groups. Most frequent TEAEs were known adverse drug reactions of dapoxetine treatment including nausea (9.2%), headache (4.4%), diarrhea (3.6%), dizziness (2.4%), and dizziness postural (2.4%). CONCLUSIONS: In men with PE and comorbid ED on a stable regimen of PDE5 inhibitor, dapoxetine provided meaningful treatment benefit and was generally well tolerated.

Cardiovascular safety profile of dapoxetine during the premarketing evaluation.

The cardiovascular safety profile of dapoxetine, a novel selective serotonin reuptake inhibitor (SSRI) developed as an on-demand oral treatment for premature ejaculation (PE) in men, is evaluated. The cardiovascular assessment of dapoxetine was conducted throughout all stages of drug development, with findings from preclinical safety pharmacology studies, phase I clinical pharmacology studies investigating the effect of dapoxetine on QT/corrected QT (QTc) intervals in healthy men, and phase III, randomized, placebo-controlled studies evaluating the safety (and efficacy) of the drug. Preclinical safety pharmacology studies did not suggest an adverse electrophysiologic or hemodynamic effect with concentrations of dapoxetine up to 2-fold greater than recommended doses. Phase I clinical pharmacology studies demonstrated that dapoxetine did not prolong the QT/QTc interval and had neither clinically significant electrocardiographic effects nor evidence of delayed repolarization or conduction effects, with dosing up to 4-fold greater than the maximum recommended dosage. Phase III clinical studies of dapoxetine in men with PE indicated that dapoxetine was generally safe and well tolerated with the dosing regimens used (30 mg and 60 mg as required). Events of syncope were reported during the clinical development program, with the majority occurring during study visits (on site) on day 1 following administration of the first dose when various procedures (e.g. orthostatic maneuvers, venipunctures) were performed, suggesting that the procedures contributed to the incidence of syncope. This was consistent with previous reports showing that these and similar factors contribute to or trigger vasovagal syncope. Findings of the dapoxetine development program demonstrate that dapoxetine is associated with vasovagal-mediated (neurocardiogenic) syncope. No other associated significant cardiovascular adverse events were identified.

Efficacy and safety of dapoxetine for the treatment of premature ejaculation: integrated analysis of results from five phase 3 trials.

INTRODUCTION: Dapoxetine has been evaluated for the on-demand treatment of premature ejaculation (PE) in five phase 3 studies in various populations worldwide and has recently been approved in several countries. AIM: To present integrated efficacy and safety data from phase 3 trials of dapoxetine. METHODS: Data were from five randomized, multicenter, double-blind, placebo-controlled studies conducted in over 25 countries. Men (N=6,081)≥18 years who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision criteria for PE; four studies required a baseline intravaginal ejaculatory latency time (IELT) of ≤2 minutes. Dapoxetine 30 and 60 mg on demand (prn; 1-3 hours before intercourse) were evaluated for either 12 or 24 weeks in four studies; one study evaluated dapoxetine 60 mg daily (qd; included in safety assessments only) or prn for 9 weeks. MAIN OUTCOME MEASURES: End points included stopwatch-measured IELT, Premature Ejaculation Profile (PEP) items, clinical global impression of change (CGIC) in PE, and adverse events (AEs). RESULTS: Average IELT (mean [standard deviation], geometric mean [standard error]) increased from baseline (across groups, 0.9 [0.49] minutes, 0.8 [1.01] minutes) to a significantly greater extent with dapoxetine 30 (3.1 [3.91] minutes, 2.0 [1.03] minutes) and 60 mg (3.6 [3.85] minutes, 2.3 [1.03] minutes) vs. placebo (1.9 [2.43] minutes, 1.3 [1.02] minutes; P<0.001 for all) at week 12 (geometric mean fold increase, 2.5, 3.0, and 1.6, respectively). All PEP items and CGIC improved significantly with both doses of dapoxetine vs. placebo (P<0.001 for all). The most common AEs included nausea, dizziness, and headache, and evaluation of validated instruments demonstrated no anxiety, akathisia, suicidality, or changes in mood with dapoxetine use and no discontinuation syndrome following abrupt withdrawal. CONCLUSIONS: In this diverse population, dapoxetine significantly improved all aspects of PE and was generally well tolerated.

Baseline characteristics and treatment outcomes for men with acquired or lifelong premature ejaculation with mild or no erectile dysfunction: integrated analyses of two phase 3 dapoxetine trials.

INTRODUCTION: Premature ejaculation (PE) is classified as an acquired or lifelong condition but data on baseline characteristics and response to treatment of men with acquired or lifelong PE and mild erectile dysfunction (ED) or normal erectile function (EF) is limited. AIM: To present integrated analyses of baseline characteristics and treatment outcomes from phase 3 dapoxetine trials in men with acquired or lifelong PE and mild or no ED. METHODS: Data were analyzed from two randomized, double-blind, placebo-controlled, phase 3 clinical trials (International and Asia-Pacific) that evaluated efficacy and safety of dapoxetine (30 mg or 60 mg as needed [PRN]) in patients with PE. Men were ≥18 years, in a stable monogamous relationship for ≥6 months, met DSM-IV-TR criteria for PE for ≥6 months, had an International Index of Erectile Function EF domain score ≥21, and had an intravaginal ejaculatory latency time (IELT) ≤2 minutes in ≥75% of intercourse episodes. MAIN OUTCOME MEASURES: Demographics, sexual history, and PE symptomatology at baseline, and mean IELT and patient-reported outcomes (PROs) at study end (week 12), were analyzed for men with acquired or lifelong PE and mild or no ED (EF score 21-25 vs. ≥26). RESULTS: Baseline characteristics except duration of PE were similar in men with acquired and lifelong PE, with no other differentiating features by ED status. Dapoxetine treatment improved significantly mean IELT (arithmetic and geometric) and PRO responses (perceived control over ejaculation, satisfaction with sexual intercourse, ejaculation-related personal distress, and interpersonal difficulty) for acquired and lifelong subtypes, but presence of mild ED diminished PRO responsiveness in both subtypes, particularly those with lifelong PE. CONCLUSIONS: Baseline characteristics and treatment outcomes were generally similar in men with acquired and lifelong PE. The presence of mild ED appears to be associated with a more modest treatment response, irrespective of lifelong or acquired PE subtype.

Validity of the patient-reported Clinical Global Impression of Change as a measure of treatment response in men with premature ejaculation.

INTRODUCTION: The Clinical Global Impression of Change (CGIC) measures have high utility in clinical practice. However, it is unknown whether the CGIC is valued for assessing premature ejaculation (PE) symptoms and/or the relationship between CGIC and other validated PE patient-reported measures. AIM: The study aims to assess the validity of the patient-reported CGIC measure in men with PE and to examine the relationship between CGIC ratings and assessments of control, satisfaction, personal distress, and interpersonal difficulty. METHODS: Data from a randomized, double-blind, 24-week phase 3 trial in 1,162 men with PE who received dapoxetine (30 mg or 60 mg) or placebo on demand provided the basis for the analysis. Patients were ≥18 years, in a stable monogamous relationship for ≥6 months, met the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revision criteria for PE for ≥6 months, and had an intravaginal ejaculatory latency time (IELT) ≤2 minutes in ≥75% of intercourse episodes. MAIN OUTCOME MEASURES: The CGIC asked patients to rate improvement or worsening of their PE compared with the start of the study using a 7-point response scale; other patient-reported measures were control over ejaculation, satisfaction with sexual intercourse, interpersonal difficulty, and personal distress related to ejaculation. Stopwatch-measured IELT was recorded. Associations between CGIC and change in other measures at study end point were assessed. RESULTS: The magnitude of IELT increased for each category of improvement on the CGIC: 1.63, 4.03, and 7.15 minutes for slightly better, better, and much better, respectively. Higher CGIC ratings were correlated with greater improvement in control (r = 0.73), satisfaction (r = 0.62), greater reduction in distress (r = -0.52), and interpersonal difficulty (r = -0.39). Total variance accounted for was 57.4%: control (48.7%), satisfaction (4.5%), IELT (2.8%), and distress (1.15%). CONCLUSIONS: The analyses support the validity of the CGIC measure in men with PE. The CGIC can provide clinicians in practice with a valid and brief outcome assessment of their patient's condition.

Pharmacokinetics of dapoxetine hydrochloride in healthy Chinese, Japanese, and Caucasian men.

Dapoxetine is a short-acting selective serotonin reuptake inhibitor developed for the on-demand treatment of premature ejaculation and is approved in some European Union countries, as well as Mexico and Korea, for this indication. The pharmacokinetics of dapoxetine 30 mg and 60 mg in healthy Chinese (single dose), Japanese, and Caucasian men (single and multiple dose) were assessed in 2 studies. In the 3 ethnic groups, dapoxetine was rapidly absorbed following oral administration, with peak plasma concentrations evident approximately 1 hour after dosing, independent of dose, dosing frequency (single or multiple dosing), or ethnicity. Dapoxetine was eliminated in a biphasic manner with an apparent mean terminal half-life of 14 to 17 hours. There was a dose-proportional increase in dapoxetine maximum plasma concentration (C(max)) and area under concentration-time curves (AUCs). The single-dose pharmacokinetic parameters of dapoxetine metabolites were also similar for the 3 ethnic groups, as were the pharmacokinetics of dapoxetine and its metabolites following single and multiple dosing in Caucasian and Japanese men. Dapoxetine was well tolerated by all 3 ethnic groups.

Pharmacokinetic, pharmacodynamic, and electrocardiographic effects of dapoxetine and moxifloxacin compared with placebo in healthy adult male subjects.

Selective serotonin reuptake inhibitors (SSRIs) may be associated with electrocardiographic effects. The electrocardiographic pharmacodynamics of dapoxetine, a short-acting SSRI being developed for the treatment of premature ejaculation, are compared with those of placebo and moxifloxacin (positive control) in 2 single-center, randomized, crossover studies in healthy men. In study 1, subjects receive 2 doses of dapoxetine 120 mg, given 3 hours apart; a single dose of moxifloxacin 400 mg; and 2 doses of placebo, given 3 hours apart. In study 2, subjects receive single doses of dapoxetine 60 mg, dapoxetine 120 mg, moxifloxacin 400 mg, and placebo. Moxifloxacin significantly increases QT and corrects QT intervals (QTc) compared with placebo in both studies (eg, Bazett-corrected QTc of 11.90 milliseconds [95% confidence interval, 2.68 to 21.11] and 5.06 [95% confidence interval, -2.26 to 12.38]). Dapoxetine 60, 120, and 240 mg do not prolong the QT/QTc interval and have no clinically significant electrocardiographic effects. Dapoxetine and moxifloxacin pharmacokinetics are similar to previous reports. Adverse events are generally mild in severity; nausea is the most common. The results demonstrate that dapoxetine does not have electrocardiographic effects at doses of 60, 120, and 240 mg.

Efficacy and safety of extended-release oxybutynin in combination with tamsulosin for treatment of lower urinary tract symptoms in men: randomized, double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy and tolerability of extended-release oxybutynin in combination with the alpha1-blocker tamsulosin in reducing lower urinary tract symptoms in men. PATIENTS AND METHODS: In this multicenter, double-blind trial performed between March 29, 2004, and June 22, 2005, 420 men aged 45 years or older with a total International Prostate Symptom Score (IPSS) of 13 or more and IPSS for storage of 8 or more were randomized to receive tamsulosin (0.4 mg/d) with either extended-release oxybutynin (10 mg/d) or placebo for 12 weeks. Eligibility requirements included a maximum flow rate of 8 mL/s or more with voided volume of 125 mL or more and a postvoid residual volume of 150 mL or less on 2 occasions. Postvoid residual volume and peak flow rates at weeks 4, 8, and 12 were measured. The primary end point was change from baseline in total IPSS after 12 weeks of treatment. Secondary outcomes included change in IPSSs for storage and quality of life. RESULTS: Tamsulosin combined with extended-release oxybutynin resulted in significantly greater improvement in total IPSS compared with tamsulosin and placebo after 8 (P=.03) and 12 (P=.006) weeks of treatment, and improved IPSS for storage and quality of life at all assessment points (P<.01). The incidence of postvoid residual volume higher than 300 mL was 2.9% (6/209) in patients receiving combination therapy compared with 0.5% (1/209) in patients receiving tamsulosin alone (P=.12). Occurrence of peak flow rates below 5 mL/s was 3.8% (8/209) for combination therapy and 5.7% (12/209) for tamsulosin alone (P=.49). CONCLUSION: In men with substantial storage symptoms, combination therapy with tamsulosin and extended-release oxybutynin demonstrated greater efficacy than and comparable safety and tolerability to tamsulosin monotherapy.