Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new detrol research articles will be listed here shortly after becoming available to us.
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Medical research on detrol
Curr Med Res Opin. 2008 Jun 18;
Speakman M, Khullar V, Mundy A, Odeyemi I, Bolodeoku J
OBJECTIVE: To evaluate the cost-utility of solifenacin, a new generation antimuscarinic, compared with tolterodine in the treatment of overactive bladder syndrome (OAB), from the perspective of the UK National Health Service (NHS).RESEARCH DESIGN AND METHODS: A 1-year Markov model was constructed using data from a 12-week, randomised, double-blind study that compared flexible dosing with solifenacin (5 mg and 10 mg) with tolterodine (IR 2 mg bd/ER 4 mg) in adults with OAB. The model incorporated five discrete health states that were based on disease severity (micturitions/day and incontinence episodes/day). A 'drop out' state was also used in the model to account for patients that discontinued treatment in the first year. UK-specific costs for drug treatment and pad use as well as utilities were assigned to each health state. RESULTS: Solifenacin was a less costly and more effective treatment strategy compared with tolterodine. During the course of 1 year, the estimated cost per patient was pound509 for patients treated with solifenacin and pound526 for those given tolterodine, a cost saving of pound17 per patient. Treatment with solifenacin was also associated with a small incremental gain of 0.004 quality-adjusted-life-years (QALYs) over tolterodine. Sensitivity analysis suggests that the incremental cost effectiveness of solifenacin relative to tolterodine does not appear to exceed pound30 000/QALY with even large variations in key model parameters.CONCLUSION: Flexible dosing with solifenacin is likely to be cost-effective versus tolterodine in the treatment of OAB. Further studies are needed to confirm these results.
Impact of fesoterodine on quality of life: pooled data from two randomized trials.
BJU Int. 2008 Jul; 102(1): 56-61
Kelleher CJ, Tubaro A, Wang JT, Kopp Z
OBJECTIVE: To evaluate the effect of fesoterodine on health-related quality of life (HRQoL) in patients with overactive bladder (OAB) syndrome. PATIENTS AND METHODS: Pooled data from two randomized placebo-controlled phase III studies were analysed. Eligible patients with frequency and urgency or urgency urinary incontinence were randomized to placebo or fesoterodine 4 or 8 mg for 12 weeks; one trial also included tolterodine extended release (tolterodine-ER) 4 mg. HRQoL was assessed using the King's Health Questionnaire (KHQ), International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), a six-point Likert scale measuring the severity of bladder-related problems, and treatment response. RESULTS: By the end of treatment, all active-treatment groups had significantly improved HRQoL compared with those on placebo, as shown by an improvement in the KHQ and ICIQ-SF scores, treatment response rate, and a major improvement in self-reported bladder-related problems. The fesoterodine 8-mg group had statistically significant improvements over placebo in eight of nine KHQ domains. Fesoterodine 4 mg and tolterodine-ER produced statistically significant improvements in seven of nine KHQ domains. Fesoterodine 8 mg gave better results than 4 mg in two domains; Emotions and Symptom Severity (P < 0.05). A major improvement (>or=2 points) in bladder-related problems was reported by 33% of patients on fesoterodine 4 mg, 38% on fesoterodine 8 mg, and 34% on tolterodine-ER, vs 21% on placebo (P < 0.001). CONCLUSIONS: Fesoterodine significantly improved HRQoL in patients with OAB. Both fesoterodine 4 and 8 mg produced significant improvements on most KHQ domains, the ICIQ-SF, treatment response rate, and a Likert scale measuring bladder-related problems.
Urgency in overactive bladder: Translating experimental data into clinical practice.
Drugs Today (Barc). 2008 May; 44(5): 381-9
Wyndaele JJ, De Wachter S
In overactive bladder (OAB) syndrome, urgency is considered to be the key symptom that generates or affects all other symptoms. Urgency has been defined by the latest International Continence Society (ICS) terminology report as "the complaint of a sudden compelling desire to pass urine, which is difficult to defer". This definition has caused some debate and a final terminology has not yet been agreed upon. However, many would agree that urgency is different from urge when describing bladder sensation, and "urgency" has become one of the leading topics in OAB diagnosis and a primary endpoint in evaluation of treatment. Despite the many potential targets for pharmacological treatment, few drugs other than antimuscarinic agents have passed the proof-of-concept stage. There are multiple mechanisms, some proven in concept but more theoretical, by which a pharmacological agent may facilitate lower urinary tract filling/urine storage, bladder sensation and bladder emptying, although organ selectivity is often a problem. Oxybutynin, tolterodine, darifenacin, solifenacin and trospium have shown superiority to placebo, with a different incidence of side effects among the different drugs. Larger randomized, controlled trials in clinical settings are required to further establish the role of these medications in the management of urgency and OAB syndrome.
BJU Int. 2008 May 26;
Kaplan SA, Roehrborn CG, Chancellor M, Carlsson M, Bavendam T, Guan Z
OBJECTIVE To evaluate the efficacy of tolterodine extended-release (ER) plus tamsulosin on lower urinary tract symptoms (LUTS) as assessed by changes in the International Prostate Symptom Score (IPSS) in men who met symptom entry criteria for both overactive bladder (OAB) and benign prostatic hyperplasia (BPH) trials. PATIENTS AND METHODS Men aged >/=40 years with an IPSS of >/=12 and diary-documented OAB symptoms (>/=8 voids/24 h and >/=3 urgency episodes/24 h, with or without urgency urinary incontinence) who reported at least moderate problems related to their bladder condition were randomized to receive placebo, tolterodine ER (4 mg), tamsulosin (0.4 mg), or tolterodine ER (4 mg) + tamsulosin (0.4 mg) once daily for 12 weeks. Patients completed the IPSS at baseline and at 1, 6 and 12 weeks. RESULTS Patients receiving tolterodine ER + tamsulosin had significantly greater improvements than those taking placebo on IPSS storage subscale scores and scores for all three individual storage items included on the IPSS (urinary frequency, urgency, and nocturnal micturitions) by 12 weeks. Storage subscale and urgency scores were significantly improved vs placebo at 1 and 6 weeks, whereas frequency scores were significantly improved at 6 weeks. Changes in IPSS storage subscale and individual storage item scores in the tolterodine ER and tamsulosin monotherapy groups were not significantly different from placebo at most time points. IPSS voiding subscale scores and scores for three of four individual voiding items (sensation of incomplete emptying, intermittency, and weak stream) were significantly improved by 12 weeks for patients receiving tamsulosin monotherapy vs placebo. Voiding subscale and intermittency scores were significantly improved vs placebo at 1 week; weak stream scores were significantly improved at 1 and 6 weeks. The IPSS voiding subscale and individual voiding item scores in the tolterodine ER + tamsulosin and tolterodine ER groups were not significantly different from placebo at most time points. CONCLUSIONS In this distinct clinical research population of men who met traditional symptom entry criteria for both OAB and BPH trials, tolterodine ER + tamsulosin was significantly more effective than placebo in treating storage LUTS, including OAB symptoms. Tamsulosin monotherapy produced significant improvements in voiding LUTS.
Anticholinergic Activity of 107 Medications Commonly Used by Older Adults.
J Am Geriatr Soc. 2008 May 26;
Chew ML, Mulsant BH, Pollock BG, Lehman ME, Greenspan A, Mahmoud RA, Kirshner MA, Sorisio DA, Bies RR, Gharabawi G
The objective of this study was to measure the anticholinergic activity (AA) of medications commonly used by older adults. A radioreceptor assay was used to investigate the AA of 107 medications. Six clinically relevant concentrations were assessed for each medication. Rodent forebrain and striatum homogenate was used with tritiated quinuclidinyl benzilate. Drug-free serum was added to medication and atropine standard-curve samples. For medications that showed detectable AA, average steady-state peak plasma and serum concentrations (C(max)) in older adults were used to estimate relationships between in vitro dose and AA. All results are reported in pmol/mL of atropine equivalents. At typical doses administered to older adults, amitriptyline, atropine, clozapine, dicyclomine, doxepin, L-hyoscyamine, thioridazine, and tolterodine demonstrated AA exceeding 15 pmol/mL. Chlorpromazine, diphenhydramine, nortriptyline, olanzapine, oxybutynin, and paroxetine had AA values of 5 to 15 pmol/mL. Citalopram, escitalopram, fluoxetine, lithium, mirtazapine, quetiapine, ranitidine, and temazepam had values less than 5 pmol/mL. Amoxicillin, celecoxib, cephalexin, diazepam, digoxin, diphenoxylate, donepezil, duloxetine, fentanyl, furosemide, hydrocodone, lansoprazole, levofloxacin, metformin, phenytoin, propoxyphene, and topiramate demonstrated AA only at the highest concentrations tested (patients with above-average C(max) values, who receive higher doses, or are frail may show AA). The remainder of the medications investigated did not demonstrate any AA at the concentrations examined. Psychotropic medications were particularly likely to demonstrate AA. Each of the drug classifications investigated (e.g., antipsychotic, cardiovascular) had at least one medication that demonstrated AA at therapeutic doses. Clinicians can use this information when choosing between equally efficacious medications, as well as in assessing overall anticholinergic burden.
Int Urogynecol J Pelvic Floor Dysfunct. 2008 May 27;
Chuang YC, Thomas CA, Tyagi S, Yoshimura N, Tyagi P, Chancellor MB
The objective of the study was to evaluate the local effects of three antimuscarinics excreted into human urine after oral ingestion. Two normal adult collected their voided urine after taking oral doses of tolterodine, darifenacin, and solifenacin for 7 days with a 14-day washout period. The urodynamic effect of intravesically administered human urine on carbachol-induced bladder overactivity was studied in female rats. Cystometric parameters were measured during continuous infusion of saline and human urine and then a mixture of carbachol (30 microM) and human urine. Carbachol significantly reduced the intercontraction interval and bladder capacity in the control (urine taken in the absence of oral antimuscarinics) and tolterodine- or darifenacin-administered groups. However, human urine obtained after taking solifenacin prevented the carbachol-induced detrusor overactivity. Urine excreted after oral ingestion of solifenacin provides a localized pharmacological advantage for the treatment of the overactive bladder syndrome.
Hyponatremia associated with tolterodine therapy.
Am J Health Syst Pharm. 2008 Jun 1; 65(11): 1054-6
Madewell KA, Kuo P
PURPOSE: The case of a patient who developed hyponatremia after recent initiation of tolterodine is reported. SUMMARY: An 86-year-old woman arrived at the hospital due to an acute change in her mental status. The patient's daughter found her mother slumped over and stated that she was unresponsive for approximately four minutes. The admitting diagnosis was transient ischemic attack or syncope. Baseline laboratory tests revealed an abnormal basic metabolic panel, including a serum sodium concentration of 125 mmol/L and a serum chloride concentration of 88 mmol/L. The results of a complete blood count and thyroid function tests were within normal limits. Unsuccessful attempts at sodium correction included initial fluid restriction and, later, the administration of 0.9% sodium chloride injection over 24 hours. Physiological causes of hyponatremia were ruled out. The attending physician and team pharmacist reviewed the patient's medication profile for potential causes of hyponatremia. Hydrochlorothiazide, a home medication for the patient, was discontinued at hospital admission and ruled out as a cause of her hyponatremia. A documented association between lisinopril, mirtazapine, or omeprazole and hyponatremia exists in various case reports. However, per the patient's primary care physician, tolterodine was the only modification of an otherwise stable medication profile at an outpatient office visit approximately four weeks prior to admission. Once tolterodine was discontinued, the patient's hyponatremia quickly resolved. Tolterodine was discontinued on hospital day 5, and the hyponatremia was corrected by the next day. CONCLUSION: An 86-year-old woman developed hyponatremia after recent initiation of tolterodine therapy.
Int J Clin Pract. 2008 Jun; 62(6): 925-31
Coyne KS, Elinoff V, Gordon DA, Deng DY, Brodsky M, Glasser DB, Jumadilova Z, Carlsson M
AIMS: Relationships were evaluated between treatment-related improvements in overactive bladder (OAB) symptoms as recorded in bladder diaries and patient-reported symptom bother, bladder-related problems and health-related quality of life (HRQL). METHODS: A post hoc analysis was performed on data from patients with OAB (n = 863) enrolled in a 12-week open-label trial of tolterodine extended release (ER) in a primary care setting. At baseline and week 12, patients recorded every micturition, urgency episode and urgency urinary incontinence episode in 3-day bladder diaries. Patients also completed the Overactive Bladder Questionnaire (OAB-q) and Patient Perception of Bladder Condition (PPBC). Relationships between week 12 changes in bladder diary variables and OAB-q and PPBC scores were evaluated using Spearman correlations. RESULTS: By week 12, tolterodine ER-related improvements in all bladder diary variables were significantly correlated with improvements on the PPBC (r = 0.26-0.36; p < 0.001), OAB-q Symptom Bother scale (r = 0.30-0.51; p < 0.001), and all OAB-q HRQL domains (r = -0.24 to -0.42; p < 0.001), although the correlations were generally small to moderate in size. Improvements on the PPBC were also significantly correlated with improvements on the OAB-q Symptom Bother scale (r = 0.63; p < 0.001) and all HRQL domains (r = -0.40 to -0.59; p < 0.001). CONCLUSIONS: Tolterodine ER-related improvements in OAB symptoms (assessed by diary variables) and patients' perceptions of the changes in symptom bother, bladder-related problems and HRQL (assessed by PPBC and OAB-q) were significantly correlated. The OAB-q and the PPBC provide a relevant and important patient perspective for OAB treatment evaluation.
Int Braz J Urol. 2008 Mar-Apr; 34(2): 250-1
Snow BW
J Manag Care Pharm. 2008 Apr; 14(3): 291-301
D'Souza AO, Smith MJ, Miller LA, Doyle J, Ariely R
BACKGROUND: Pharmacotherapy constitutes an important adjunct to behavioral therapy for the treatment of overactive bladder (OAB). Tolterodine and oxybutynin are commonly prescribed drugs for OAB treatment that exert their beneficial effect by suppressing bladder muscle contractions. However, high discontinuation rates have been observed for these drugs in clinical trials, as well as in real-world settings, in part due to adverse effects. Extended-release (ER) formulations were introduced with an improved tolerability profile over immediate-release (IR) versions of the 2 drugs. No study has compared persistence and adherence to therapy for both the ER and IR versions of tolterodine and oxybutynin. OBJECTIVE: To compare persistence, adherence, and switch rates for the IR and ER formulations of oxybutynin and tolterodine for patients enrolled in a regional managed care plan. METHODS: Study patients were adults (aged e 18 years), with at least 1 pharmacy claim for either tolterodine extended-release (tol-ER), oxybutynin extended-release (oxy-ER), tolterodine immediate-release (tol-IR), or oxybutynin immediate-release (oxy-IR) during the period from July 1, 1999, to December 31, 2003, and were continuously eligible for benefits from 6 months before through 12 months after the initial OAB pharmacy claim (index) date. A retrospective cohort study design was used following patients from the index date to the occurrence of non-persistence with the index medication (i.e., a gap of > 45 days between successive prescription fills or a switch to any other OAB medication), or the end of a 1-year follow-up period, through December 31, 2004. Switching was defined as any change from the index medication, including a change in dose form (e.g., tol-IR to tol-ER), to one of the other 3 study drugs, or to a different OAB treatment (e.g., trospium chloride, oxybutynin patch, flavoxate, hyoscyamine sulfate, or propantheline bromide) during the follow-up period. Adherence was measured as the proportion of patients with a medication possession ratio (MPR) of at least 80%. MPR was calculated as (1) the sum of days supply for all pharmacy claims except the last pharmacy claim, divided by (2) the total number of days from the first fill date to the fill date of the last pharmacy claim. The association of drug therapy with study outcomes was assessed with bivariate and adjusted (multivariate) analyses. Multivariate analyses controlled for demographic and clinical characteristics, plan type, patient out-of-pocket cost for the index medication, and year of therapy initiation. RESULTS: 1,117 patients had at least 1 pharmacy claim for an OAB study drug (n = 454 for tol-ER [40.6%], n = 249 for oxy-ER [22.3%], n = 306 for tol-IR [27.4%], n = 108 for oxy-IR [9.7%]), of whom 81.6% were women. The mean (standard deviation [SD]) age of the study population was 55.7 (14.5) years. Only 53.7% had at least 1 OAB diagnosis recorded during the 18-month eligibility period. 44.5% of patients did not have a refill after the initial (index) pharmacy claim (39.4% for oxy-ER, 42.7% for tol-ER, 46.1% for tol-IR, and 59.3% for oxy-IR; P = 0.004). Only 13.2% persisted with treatment for at least 1 year (tol-ER = 15.0%, oxy-ER = 15.3%, tol-IR = 11.4%, oxy-IR = 6.5%; P = 0.050). The median days to discontinuation (non-persistency) were 31.0 overall, 33.0 for tol-ER, 34.0 for oxy-ER, 32.0 for tol-IR, and 0 for oxy-IR; P = 0.010. The overall switch rate as a percentage of all study patients was 13.3%, ranging from 9.9% for tol-ER, 13.7% for tol-IR, 16.5% for oxy-ER, and 19.4% for oxy-IR; P = 0.020. Of patients who refilled their initial prescription at least once, 24.0% made a medication switch. Adherence rates as measured by percentage of patients with MPR >or= 80% were 30.3% overall and higher for the ER formulations: 35.2% for tol-ER, 36.1% for oxy-ER, 23.5% for tol-IR, and 14.8% for oxy-IR; P < 0.001. CONCLUSIONS: Adherence was significantly better for ER than IR agents. The high rate of non-persistence (44.5%) following the first (index) prescription highlights the need for medication counseling by health care professionals.