imidafenacin and propiverine

To carry out a network meta-analysis of randomised controlled trials (RCTs) of anticholinergic drug treatment for people with overactive bladders.. Comprehensive searches for relevant RCTs were carried out starting with RCTs included in previous systematic reviews with the last search in February 2017. Searches included terms for the anticholinergic drugs tolterodine, oxybutynin, trospium, propiverine, solifenacin, darifenacin, imidafenacin, and fesoterodine. Data was extracted from the systematic reviews or reports of studies for cure or improvement, voids per 24 hr, leakage episodes per 24 hr and dry mouth. Data was analysed using frequentist network meta-analysis.. 128 studies were found. There was no clearly best treatment for cure or improvement. The differences between treatments for voids and leakages were small and unlikely to be of clinical importance. Transdermally delivered oxybutynin was clearly the best treatment for dry mouth but was still worse than placebo.. All the anticholinergic drugs were better than placebo but apart from dry mouth were similar in effect. Transdermal oxybutynin caused less dry mouth than the other treatments, so may be worth considering as the first treatment.

Topics: Benzhydryl Compounds; Benzilates; Benzofurans; Cholinergic Antagonists; Humans; Imidazoles; Mandelic Acids; Network Meta-Analysis; Pyrrolidines; Solifenacin Succinate; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

We carried out a systematic review and meta-analysis to assess the efficacy and safety of imidafenacin for treating overactive bladder in adult.. A literature review was performed to identify all published randomized placebo-controlled trials of imidafenacin for the treatment of OAB. The search included the following databases: MEDLINE, EMBASE. The reference lists of retrieved studies were also investigated.. Five publications involving a total of 1,428 patients were used in the analysis, which compared imidafenacin with propiverine and solifenacin. We found that imidafenacin was effective in treating OAB in our meta-analysis, which was similar to propiverine in its efficacy. The mean number of UI per week (the standardized mean difference (SMD) = 1.23, 95% CI -0.19 to 2.65, p = 0.09), the mean number of urgency episodes per day (SMD = 0.26, 95% CI -0.11 to 0.63, p = 0.17), the mean number of micturitions per day (SMD = 0.01, 95% CI -0.30 to 0.31, p = 0.96), and the mean urine volume (ml) per micturition (SMD = -13.04, 95% CI -20.45 to -5.62, p = 0.0006) indicated that imidafenacin was similar to propiverine in its efficacy. Mean OABSS (SMD = 0.48, 95% CI -0.08 to 1.03, p = 0.09) indicated that imidafenacin was also similar to solifenacin in its efficacy. Besides, imidafenacin was better tolerated than propiverine in the safety, indicated by dry mouth (OR 0.73, 95% CI 0.54-0.98, p = 0.04) and any adverse events (OR 0.63, 95% CI 0.46-0.88, p = 0.006). Moreover, imidafenacin was also better tolerated than solifenacin in the safety, indicated by constipation (OR 0.21, 95% CI 0.08-0.53, p = 0.001) and any adverse events (OR 0.33, 95% CI 0.15-0.71, p = 0.004).. This meta-analysis indicates that imidafenacin was similar to propiverine or solifenacin in its efficacy for OAB and was better tolerated than propiverine or solifenacin in the safety for OAB. We conclude that imidafenacin is preferable to propiverine or solifenacin from a perspective of safety.

Topics: Adult; Benzilates; Constipation; Humans; Imidazoles; Randomized Controlled Trials as Topic; Solifenacin Succinate; Urinary Bladder, Overactive; Urological Agents; Xerostomia

Antimuscarinics (AMs) are the mainstay of pharmacological treatment of overactive bladder (OAB), a symptom complex defined by the presence of urinary urgency, usually associated with frequency and nocturia, with or without urgency urinary incontinence. The AMs used to treat OAB differ in their pharmacological profiles, which may affect their potential for causing adverse effects (AEs).. The present article aims to review the literature about pharmacokinetics (PK) of the different AMs used in the treatment of OAB. Furthermore, the AEs related to the use of these drugs and their incidence are presented. This systematic review is based on material searched and obtained via Medline, Pubmed and EMBASE up to March 2012 using the search terms "adverse events, pharmacokinetics, tolerability" in combination with "darifenacin, fesoterodine, imidafenacin, oxybutynin, propiverine, solifenacin, tolterodine, and trospium.". Antimuscarinics are the first-line pharmacological treatment for OAB. Despite the development of new molecules that improve their efficacy/safety profile, there are some drugs that are pharmacokinetically more appropriate to be prescribed in specific populations such as patients with neurological disease or the elderly. Moreover, research should be encouraged in evaluating antimuscarinics in conjunction with other drugs such as estrogens or beta-agonists. The identification of prognostic criteria for pharmacological therapy would be helpful.

Topics: Benzhydryl Compounds; Benzilates; Benzofurans; Chronic Disease; Cresols; Drug Combinations; Female; Humans; Imidazoles; Mandelic Acids; Muscarinic Antagonists; Nocturia; Phenylpropanolamine; Pyrrolidines; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Urinary Bladder, Overactive; Urinary Incontinence

This analysis was conducted to investigate the cardiovascular (CV) safety outcomes from the MILAI II study. MILAI II was conducted to evaluate the long-term safety and efficacy of antimuscarinic add-on therapy to mirabegron over 52 weeks in patients with overactive bladder (OAB) symptoms.. MILAI II consisted of a 2-week screening period (patients received mirabegron 50 mg once daily) plus a 52-week treatment period (patients were randomized to receive a combination of mirabegron 50 mg/d plus solifenacin 5 mg/d, propiverine 20 mg/d, imidafenacin 0.2 mg/d, or tolterodine 4 mg/d). CV safety was assessed using treatment-emergent adverse events (TEAEs), vital signs, and 12-lead electrocardiograms (ECGs). Vital signs and ECG data were evaluated for each patient using worst post-baseline values reported.. Of 647 patients, 570 (88.1%) were female with a mean age of 65 years. CV history at baseline and CV-related concomitant medication use throughout the study were balanced between groups. The incidences of overall and drug-related CV TEAEs were ≤8.1% and ≤6.2%, respectively, for all groups. The most common TEAEs were ECG T wave amplitude decreased, ECG QT prolonged, and ventricular extrasystoles. Overall, 36 TEAEs of interest related to the CV system that were possibly/probably related to treatment were reported with similar incidences for each group. For the worst post-baseline vital signs and ECGs, no relationships were noted in terms of either timing or treatment group.. A favorable CV safety profile was observed following long-term combination treatment with mirabegron and an antimuscarinic in patients with OAB symptoms.

Topics: Acetanilides; Aged; Aged, 80 and over; Benzilates; Cardiovascular Diseases; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Imidazoles; Japan; Male; Middle Aged; Muscarinic Antagonists; Solifenacin Succinate; Thiazoles; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urological Agents

To evaluate the long-term safety (primary objective) and efficacy (secondary objective) of antimuscarinic add-on therapy in patients receiving mirabegron.. During a 2-week screening period, patients (aged ≥20 years, mirabegron treatment for ≥6 weeks, residual overactive bladder symptoms) received mirabegron 50 mg once daily. These patients were subsequently randomized to 52 weeks' treatment with mirabegron 50 mg/day plus an antimuscarinic (solifenacin 5 mg, propiverine 20 mg, imidafenacin 0.2 mg, or tolterodine 4 mg) with the potential to double the antimuscarinic dose (except for tolterodine) at week 8. Safety assessments included treatment-emergent adverse events, vital signs, 12-lead electrocardiograms, post-void residual volume, and laboratory evaluations. Efficacy was assessed using changes from baseline in overactive bladder symptom score total score; overactive bladder questionnaire short form score; micturitions, urgency episodes, urinary incontinence episodes, and urgency urinary incontinence episodes/24 h; mean volume voided per micturition; and number of night-time micturitions.. Overall, 80.2% of patients (88.1% women, mean age 65 years) experienced at least one treatment-emergent adverse event, with similar rates for all treatments. The adverse events most commonly reported were dry mouth, nasopharyngitis, and constipation. No marked change was observed in systolic or diastolic blood pressure for any treatment, although pulse rate increased slightly in the mirabegron and propiverine, and mirabegron and tolterodine groups. For all treatments, significant improvements were observed in all efficacy parameters, including overactive bladder symptom score total and questionnaire short form scores.. Antimuscarinic add-on therapy is well tolerated and effective after initial treatment with mirabegron in patients with overactive bladder symptoms.

Topics: Acetanilides; Adrenergic beta-3 Receptor Agonists; Adult; Aged; Aged, 80 and over; Benzilates; Blood Pressure; Constipation; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Imidazoles; Japan; Male; Middle Aged; Muscarinic Antagonists; Nasopharyngitis; Severity of Illness Index; Solifenacin Succinate; Thiazoles; Time Factors; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Xerostomia

To assess the efficacy and safety of imidafenacin compared with propiverine for treatment of overactive bladder (OAB) in Korean patients.. Patients with OAB symptoms were randomised to double-blind treatment with 0.1 mg of imidafenacin twice daily (group A) or propiverine 20 mg once daily (group B) for 12-week regimen, and assessed for efficacy and safety. The primary efficacy outcome was per cent change of weekly urgency urinary incontinence (UUI) episodes at week 12. The secondary efficacy outcomes were changes in the micturitions per day, urine volume voided per micturition, urgency episodes per day, complete disappearance of incontinence episodes and severity of urgency from baseline to week 12. Quality of life and safety profiles were also compared.. Of 162 patients randomised, 140 completed the study protocol. The per cent change of weekly UUI episodes at week 12 was -69.1% in group A and -70.4% in group B (both p < 0.0001). The lower limit of 95% one-sided confidence interval of the difference between the groups was above the non-inferiority margin (-19.42%). Other voiding parameters and quality of life significantly improved at week 12 in both the groups. The discontinuation rates caused by adverse events were low in both the groups. While dry mouth was the most common adverse event (group A: 28.4% vs. B: 30.4%, p = 0.783), the severity of dry mouth was significantly less in the group A than B (p = 0.042) There were no significant differences in other safety profiles.. After the 12-week treatment of imidafenacin 0.1 mg twice daily, all OAB symptoms and quality of life improved. Imidafenacin was not inferior to propiverine for the reduction of UUI episodes, and was better tolerated than propiverine in the safety profile. Our results indicate that imidafenacin is a safe and effective drug in Korean patients with OAB.

Topics: Benzilates; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Imidazoles; Male; Middle Aged; Muscarinic Antagonists; Prospective Studies; Treatment Outcome; Urinary Bladder, Overactive; Urinary Incontinence; Urination; Urological Agents

To compare the efficacy and tolerability of imidafenacin, a novel antimuscarinic agent, with propiverine and a placebo in Japanese patients with overactive bladder (OAB).. Men and women having OAB symptoms were randomized to double-blind treatment with 0.1 mg of imidafenacin twice daily, 20 mg of propiverine once daily, or a placebo for 12 weeks, and assessed for efficacy and safety.. Overall, 781 patients were randomized to imidafenacin (324), propiverine (310), or a placebo (147). After 12 weeks of treatment, a significantly larger reduction in the mean number of incontinence episodes was observed in the imidafenacin group than in the placebo group (P < 0.0001). The non-inferiority of imidafenacin compared with propiverine was confirmed for the reduction in using incontinence episodes (P = 0.0014, non-inferiority margin: 14.5%). Imidafenacin was well tolerated. The incidence of adverse events with imidafenacin was significantly lower than with propiverine (P = 0.0101). Dry mouth, the most common adverse event, was significantly more common in the propiverine group than in the imidafenacin group (P = 0.0302). There were no significant increases in either the imidafenacin or placebo group in the mean QTc interval, whereas there was a significant increase in the mean QTc interval in the propiverine group (P < 0.0001), but there were no clinical arrhythmia and clinical arrhythmic events in any of the treatment groups.. The novel antimuscarinic agent imidafenacin at a dose of 0.1 mg twice daily was not inferior to propiverine for the reduction of incontinence episodes, and well tolerated for the treatment of OAB symptoms.

Topics: Adult; Aged; Aged, 80 and over; Asian People; Benzilates; Cholinergic Antagonists; Double-Blind Method; Female; Humans; Imidazoles; Male; Middle Aged; Muscarinic Antagonists; Placebos; Treatment Outcome; Urinary Bladder, Overactive; Young Adult

Antimuscarinics are the first-line choice of treatment for overactive bladder (OAB). Imidafenacin distributes in the bladder more selectively than in the submaxillary gland and colon, and hence, this drug is considered more useful for OAB than other antimuscarinics. However, the examination of imidafenacin selectivity to bladder over colon using in vivo models is limited. Thus, the author examined whether imidafenacin could induce more selective blockade of the bladder over colon in conscious rats using two pharmacological indices (colonic transit and neostigmine-induced fecal pellet output) and compared its bladder selectivity with propiverine. In the bladder study, the inhibitory doses of antimuscarinics were calculated using the area under the curve of the distension-induced rhythmic contraction in conscious rats. The relative bladder selectivity of imidafenacin to propiverine was 50-fold and 61-fold, respectively, in a dye marker colonic transit model and in a neostigmine-induced fecal pellet output model. This comparative study shows that the functional bladder selectivity of imidafenacin is higher than that of propiverine tested under the present conditions in conscious rats.

Topics: Animals; Benzilates; Colon; Defecation; Gastrointestinal Transit; Imidazoles; Male; Muscarinic Antagonists; Neostigmine; Rats, Sprague-Dawley; Urinary Bladder

To investigate patient satisfaction with antimuscarinic treatment of overactive bladder syndrome, and to identify factors having a significant influence on satisfaction.. A cross-sectional questionnaire survey was carried out to assess treatment satisfaction among male and female patients with overactive bladder (age ≥20 years) in the Hokuriku district of Japan. The overactive bladder symptom scores, treatment efficacies, adverse events (dry mouth and constipation), and patient satisfaction scores were investigated and compared among patients using different antimuscarinic therapeutics.. In total, 977 survey respondents (52.6% men; mean age 73.6 years) received antimuscarinic treatment. The mean overactive bladder symptom score of these patients was 6.17; in addition, 32.3% patients were satisfied with their treatment, but 33.1% were dissatisfied. Factors having a significant influence on treatment satisfaction were sex (men were less satisfied), efficacy, adverse events and the overactive bladder symptom score. Constipation negatively influenced patient satisfaction to a greater extent than did dry mouth. Patient satisfaction varied according to the drug used. Constipation was less severe with the immediate-release-type agents (imidafenacin and oxybutynin) than with the extended-release-type (propiverine, solifenacin or tolterodine).. Just one-third of Japanese Hokuriku patients with overactive bladder seem to be satisfied with their antimuscarinic treatment. Patient satisfaction is impaired by poor efficacy and the presence of adverse events; furthermore, constipation should be recognized as an adverse event that negatively influences patient satisfaction to a greater extent than dry mouth. Patient satisfaction differs according to the antimuscarinic agent used, with higher patient satisfaction being associated with less severe constipation.

Topics: Aged; Aged, 80 and over; Benzhydryl Compounds; Benzilates; Cresols; Cross-Sectional Studies; Female; Humans; Imidazoles; Japan; Male; Mandelic Acids; Middle Aged; Muscarinic Antagonists; Patient Satisfaction; Phenylpropanolamine; Quinuclidines; Solifenacin Succinate; Tetrahydroisoquinolines; Tolterodine Tartrate; Treatment Outcome; Urinary Bladder, Overactive

To investigate the effects of the antimuscarinic agent, propiverine, on the bladder and urethra in rats.. A total of 54 female rats were given propiverine, imidafenacin (an antimuscarinic agent), or distilled water by gavage once or twice daily. After 2 weeks, bladder and urethral activity were recorded under urethane anesthesia. In the propiverine group, the changes of bladder and urethral activity before and after intravenous injection of α(1) -adrenergic antagonists (prazosin, silodosin and naftopidil) were also recorded. Furthermore, the leak point pressure after electrical stimulation of abdominal wall muscles was measured in rats with vaginal distension from the control and propiverine groups.. Intravesical baseline pressure was significantly lower in the propiverine and imidafenacin groups compared with the control group, whereas the urethral baseline pressure was significantly higher in the propiverine group compared with the control or imidafenacin groups. Intravenous injection of prazosin (an α(1) -receptor antagonist) significantly decreased the urethral baseline pressure in both of the propiverine and control groups. Intravenous injection of silodosin and naftopidil (α(1A) - and α(1D) -receptor antagonists, respectively) significantly decreased the maximum contraction pressure and the urethral baseline pressure in the propiverine group. The leak point pressure of the propiverine group was significantly higher than that of the control group.. An increase of catecholamines after propiverine administration might activate smooth muscle of the proximal urethra via α(1A) - and α(1D) -adrenergic receptors, as well as activating urethral and pelvic floor striated muscle via the spinal motoneurons.

Topics: Adrenergic alpha-Antagonists; Animals; Benzilates; Female; Imidazoles; Indoles; Muscarinic Antagonists; Muscle Contraction; Muscle, Smooth; Naphthalenes; Piperazines; Prazosin; Pressure; Rats; Rats, Sprague-Dawley; Urethra; Urinary Bladder