Overactive bladder medication: Persistence, drug switching, and reinitiation

Soda, Takeshi; Tashiro, Yu; Koike, Shuhei; Ikeuchi, Ryosuke; Okada, Takuya

doi:10.1002/nau.24527

Cited by 19 publications

(37 citation statements)

References 27 publications

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“…40 Treatment persistence with mirabegron was significantly longer than that with AMs when administered as either the first-or second-line medication. 41 The PILLAR trial evaluated safety and tolerability of mirabegron in patients aged ≥65 years with OAB-wet: 42 treatment-emergent adverse events (TEAEs), the majority mild or moderate in severity, were reported in 39.4% of placebo patients and 44.2 and 49.8% of those who received mirabegron 25 mg or 50 mg, respectively, consistent with the known mirabegron safety profile. The most common TEAEs in mirabegron-treated patients were urinary tract infection, headache, and diarrhea.…”

Section: Adverse Effectsmentioning

confidence: 96%

See 1 more Smart Citation

Pharmacological Management of Urinary Incontinence: Current and Emerging Treatment

Gandi¹,

Sacco²

2021

CPAA

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Section: Adverse Effectsmentioning

confidence: 96%

“… 40 Treatment persistence with mirabegron was significantly longer than that with AMs when administered as either the first- or second-line medication. 41 …”

Section: Beta-3-agonistsmentioning

confidence: 99%

Pharmacological Management of Urinary Incontinence: Current and Emerging Treatment

Gandi¹,

Sacco²

2021

CPAA

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“…Under normal conditions, voiding is effectuated by cholinergic detrusor contractions, following muscarinic receptor activation on bladder smooth muscle cells after cholinergic neurotransmission (Andersson, 2011;Andersson and Arner, 2004). Muscarinic receptor antagonists represent the goldstandard for medical treatment of storage symptoms, but show limited efficacy with disproportional side effects, resulting in discontinuation rates up to 90% within twelve month following first prescription (Chancellor et al, 2013;Nambiar et al, 2018;Sexton et al, 2011;Soda et al, 2020). Mirabegron has been introduced as an alternative, and was initially believed to reduce symptoms by relaxation of bladder smooth muscle by activation of β 3 -adrenoceptors on bladder smooth muscle cells (Nambiar et al, 2018;Oelke et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Full Smooth Muscle Contraction in Isolated Human Detrusor Tissues by Mirabegron Is Limited to Off-Target Inhibition of Neurogenic Contractions

Huang

Tamalunas

Waidelich

et al. 2022

J Pharmacol Exp Ther

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Mirabegron is used for treatment of storage symptoms in overactive bladder (OAB), caused by spontaneous bladder smooth muscle contractions. However, owing to limitations in available studies using human tissues central questions are still unresolved, including mechanisms underlying improvements by mirabegron and its anticontractile effects in the detrusor. Here, we assessed concentration-dependent mirabegron effects on contractions of human detrusor tissues in frequence-response curves and concentration-response curves for different cholinergic and non-cholinergic agonists. Detrusor tissues were sampled from patients undergoing radical cystectomy. Contractions were induced by electric field stimulation (EFS), and by cumulative concentrations of cholinergic agonists, endothelin-1 and the thromboxane A 2 analog U46619. EFS-induced contractions were inhibited using 10 µM mirabegron, but not using 1 µM. Inhibition by 10 µM mirabegron was resistant to the β 3adrenergic antagonist L-748,337. Concentration-dependent contractions by carbachol were not inhibited by 1 µM or 10 µM mirabegron. Concentration response curves for methacholine were slightly right-shifted by 10 µM, but not 1 µM mirabegron. Concentration-dependent contractions by endothelin-1 or U46619 were not changed by mirabegron. In contrast, the muscarinic antagonist tolterodine right-shifted concentration response curves for carbachol and methacholine, and inhibited EFS-induced contractions. In conclusion, inhibition of neuogenic contractions in isolated detrusor tissues by mirabegron requires concentrations highly exceeding known plasma levels during standard dosing and the known K i values for β 3 -adrenoceptors. Full contractions by cholinerigc agonists, endothelin-1 and U46619 are not affected by therapeutic concentrations of mirabegron. Improvements of storage symptoms are most likely not imparted by inhibition of β 3 -adrenoceptors in the bladder wall itself.

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“…However, some patients experience a gradual decrease in treatment efficacy. Nearly 40% of the patients would eventually abandon the medication because of inadequate response, 5 and they are the potential candidates for further therapies.…”

Section: Introductionmentioning

confidence: 99%

Utilization rate and long‐term persistence of combination pharmacotherapy with β3‐agonists and antimuscarinics for overactive bladder refractory to monotherapy in a real‐world setting

Soda

Koike

Ikeuchi

et al. 2022

Neurourology and Urodynamics

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To assess real-world treatment profiles, including utilization rate, time to and reasons for discontinuation of combination pharmacotherapy with β 3 -agonists and antimuscarinics for refractory overactive bladder (OAB) through a retrospective chart review. Methods:We retrospectively reviewed the records of OAB patients who received β 3 -agonists or antimuscarinics at our hospital between 2012 and 2020 and analyzed the clinical course of patients who progressed to combination therapy. Data on age, sex, major complaints, OAB symptom score at the initiation of combination therapy, treatment persistence, and reasons for discontinuation were collected. Treatment persistence was assessed with respect to the median time to discontinuation and persistence rate at 12 months. Results: Of the 2163 patients receiving β 3 -agonists or antimuscarinics, only 84 (3.8%) progressed to combination therapy with both drug classes. At therapy initiation, most (98%) of these patients had moderate to severe OAB symptoms. Median treatment duration and 12-month persistence rate for combination therapy were 595 days and 64.0%, respectively. The reasons for discontinuation were insufficient treatment efficacy followed by adverse effects including voiding impairment in nearly 10% of the patients. None of the baseline parameters was independently associated with persistence in the multivariate analysis. Conclusion: While underutilized among OAB patients refractory to monotherapy, combination pharmacotherapy showed a greater persistence rate than published mirabegron or antimuscarinic monotherapy when applied to patients with moderate to severe symptoms. Treatment-emergent voiding impairment is a concern associated with this mode of therapy. A small sample size at a single institution is the limitation of this study.

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Overactive bladder medication: Persistence, drug switching, and reinitiation

Cited by 19 publications

References 27 publications

Pharmacological Management of Urinary Incontinence: Current and Emerging Treatment

Pharmacological Management of Urinary Incontinence: Current and Emerging Treatment

Inhibition of Full Smooth Muscle Contraction in Isolated Human Detrusor Tissues by Mirabegron Is Limited to Off-Target Inhibition of Neurogenic Contractions

Utilization rate and long‐term persistence of combination pharmacotherapy with β3‐agonists and antimuscarinics for overactive bladder refractory to monotherapy in a real‐world setting

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