Gerd Mürtz

Efficacy, tolerability and safety profile of propiverine in the treatment of the overactive bladder (non-neurogenic and neurogenic)

Abstract Propiverine hydrochloride (propiverine) is a compound that has neurotropic and musculotropic effects on the urinary bladder smooth muscle. Controlled clinical trials have shown its effectiveness in treating detrusor hyperreflexia and in treating patients with symptoms of an overactive bladder; this is true not only for adults but in children and the elderly as well. European and Japanese studies have also documented that propiverine is well tolerated. It is better tolerated than oxybutynin (particularly in regard to frequency and severity of dryness of the mouth). In several Japanese studies authors demonstrated that propiverine is well tolerated on a long-term basis. Voigt reported an adverse event incidence rate of 13% in a follow-up investigation during 10 years of treatment. A post-marketing drug surveillance consisting of 4390 patients provided additional data concerning efficacy and safety of propiverine. It is one of the few drugs recommended for the treatment of detrusor overactivity by the Committee on Pharmacological Treatment during the First International Consultation on Incontinence.

Efficacy, tolerability and safety of propiverine hydrochloride in comparison to oxybutynin in children with urge incontinence due to overactive bladder: Results of a multicentre observational cohort study

Study Type – Therapy (observational cohort)
Level of Evidence 2b

Propiverine vs oxybutynin for treating neurogenic detrusor overactivity in children and adolescents : results of a multicentre observational cohort study

To compare, in a retrospective observational cohort study, the efficacy, tolerability, safety and clinical effectiveness of propiverine and oxybutynin in children and adolescents with neurogenic detrusor overactivity (NDO).

Desmopressin treatment regimens in monosymptomatic and nonmonosymptomatic enuresis: A review from a clinical perspective

OBJECTIVE To evaluate outcomes of desmopressin treatment in monosymptomatic enuresis (ME) and nonmonosymptomatic enuresis (NME). MATERIALS AND METHODS PubMed was searched for all studies investigating enuresis, up to July 2009, in which desmopressin was administered alone or combined with other treatments. Each study was graded according to its respective level of evidence. RESULTS Altogether, 99 studies enrolling 7422 patients were identified as fulfilling the inclusion criteria. In 76 studies, desmopressin was administered as monotherapy; in 29 it was combined with other treatments such as antimuscarinics and enuresis alarm. CONCLUSION Studies incorporating a minor invasive versus a non-invasive diagnostic approach seem to achieve superior long-term success rates. Primary efficacy outcomes following desmopressin treatment are more favourable in ME than NME. Desmopressin administered with adjunct measures achieves superior outcomes compared to monotherapy, especially in NME. Compared to sudden withdrawal, the structured withdrawal programs show better long-term success and lower relapse rates. So far, no superiority has been shown for either time- or dose-dependent structured withdrawal programs. Most studies incorporated only small case series; only 25 studies with level of evidence 1 or 2 have been conducted. The broad range of mono- and adjunct treatments were evaluated according to the evidence based criteria recommended by the European Association of Urology.

Failure of monotherapy in primary monosymptomatic enuresis: a combined desmopressin and propiverine treatment regimen improves efficacy outcomes.

To evaluate, in a prospective study, the combination of the antimuscarinic propiverine and the antidiuretic hormone‐agonist desmopressin in children and adolescents not responsive to previous monotherapy, as in primary monosymptomatic enuresis (PME), combined treatments are considered a second‐line approach after the failure of monotherapy.

Urodynamic effects of propiverine in children and adolescents with neurogenic bladder: results of a prospective long-term study.

OBJECTIVE To evaluate prospectively the efficacy and tolerability of propiverine for long-term treatment of neurogenic detrusor overactivity (NDO) in children. MATERIALS AND METHODS 17 children and adolescents with NDO (10 female, 7 male; average age at last consultation 13.0 years) were evaluated during long-term treatment with propiverine (0.8 mg/kg body weight/day). Outcome measurements included urodynamic parameters, continence, hydronephrosis and tolerability of propiverine. RESULTS Average follow-up was 3.6 years (range 2.0-5.9). The average maximum detrusor pressure was 33.2 ± 4.8 cmH(2)O and bladder compliance was 20.0 ± 5.4 ml/cmH(2)O at the last follow-up visit. Maximum cystometric bladder capacity (MCBC) within the normal range was attained in 11 patients; it was still reduced (average of 61% of expected MCBC) in the remaining 6. Incontinence occurred on average once per day. Hydronephrosis was classified for each renal unit separately: grade 0 was measured in 26 and 22 cases, grade 1 or 2 in 6 and 8 cases, grade 3 or 4 in 2 and 4 cases pre and post treatment, respectively. In 6/17 patients adjuvant intravesical oxybutynin was applied, in 4 out of these 6 patients more invasive procedures, such as untethering, augmentation cystoplasty or botulinum toxin injections, were necessitated. Propiverine monotherapy was well tolerated in 11/17 patients. No serious adverse events were encountered during the study period. CONCLUSION Long-term efficacy and tolerability of propiverine for NDO in children and adolescents is promising: clinically relevant improvements in key urodynamic outcomes were paralleled by improvements in incontinence score.

Pharmacokinetics and Pharmacodynamics of Propiverine in Children Aged between 5 and 10 Years with Symptoms of Overactive Bladder

Background and ObjectivesPharmacokinetic studies in children are particularly required for drugs with intensive hepatic and regioselective intestinal elimination and pharmacological effects that may be critical for absorption at therapeutic doses, such as a delay in intestinal transit. One example is the antimuscarinic drug propiverine, the pharmacokinetics of which were evaluated in the present study in children with symptoms of overactive bladder.MethodsThe pharmacokinetics of immediate-release propiverine were studied in a dose-escalating, parallel-group study (propiverine 5, 10 and 15 mg twice daily for 14 days) in 25 subjects (11 females and 14 males aged 5–10 years; bodyweight 17–44 kg; body mass index 14–21 kg/m2) with symptoms of overactive bladder during waking hours. Serum concentration-time curves of propiverine and its major metabolite propiverine N-oxide (M-5) were evaluated up to 3 hours and 8 hours after the first and last administration, respectively, using liquid chromatography with tandem mass spectrometry. The voiding frequency, number of incontinence and urgency episodes, single voided volume and urine flow variables were measured before and after treatment.ResultsSignificant dose-related increases in the serum exposure (the area under the concentration-time curve, the maximum concentration and the minimum concentration) with propiverine and M-5 in the dose groups ≤0.3 mg/kg and 0.3 to ≤0.45 mg/kg after both single-dose and repeated-dose administration were found. The elimination half-lives of propiverine and M-5 at steady state were no different (mean ± SD 12.2±11.2 and 14.5 ± 9.94 hours, respectively). Higher doses did not result in additional dose-proportional increases in the respective pharmacokinetic parameters, particularly not after repeated-dose treatment. The voiding frequency, voided volume and urge symptoms were beneficially changed from baseline; significant dose-dependent changes were not observed. Most of the adverse events that were probably or possibly drug related were reported for patients in the high-dose group (>0.45 mg/kg).ConclusionsThe disposition of propiverine is dose related after repeated administration of the recommended doses below 0.45 mg/kg (0.3–0.45 mg/kg) twice daily in children aged 5–10 years with symptoms of overactive bladder and urinary incontinence. (Trial registration numbers: [clinicaltrials.gov] NCT00795925; [EudraCT] 2004-001243-30).