Long-term safety, efficacy, and tolerability of imidafenacin in the treatment of overactive bladder: a review of the Japanese literature

Abstract

Imidafenacin is an antimuscarinic agent with high affinity for the M3 and M1 muscarinic receptor subtypes and low affinity for the M2 subtype, and is used to treat overactive bladder. Several animal studies have demonstrated that imidafenacin has organ selectivity for the bladder over the salivary glands, colon, heart, and brain. In Phase I studies in humans, the approximately 2.9-hour elimination half-life of imidafenacin was shorter than that of other antimuscarinics such as tolterodine and solifenacin. Imidafenacin was approved for clinical use in overactive bladder in Japan in 2007 after a randomized, double-blind, placebo-controlled Phase II study and a propiverine-controlled Phase III study conducted in Japanese patients demonstrated that imidafenacin 0.1 mg twice daily was clinically effective for treating overactive bladder and was not inferior to propiverine for reduction of episodes of incontinence, with a better safety profile than propiverine. Several short-term clinical studies have demonstrated that imidafenacin also improves sleep disorders, nocturia, and nocturia-related quality of life. In addition, it is speculated that addon therapy with imidafenacin is beneficial for men with benign prostatic hyperplasia whose overactive bladder symptoms are not controlled by alpha-1 adrenoceptor antagonists. No cognitive impairment or influence of imidafenacin on the QTc interval has been observed. Although there have been very few relevant long-term clinical studies, the available information suggests the long-term efficacy, safety, and tolerability of imidafenacin, with less frequent severe adverse events, such as dry mouth and constipation. In addition, imidafenacin can be used safely for a long time even for cognitively vulnerable elderly patients with symptoms of overactive bladder. Thus, it is highly likely that imidafenacin is safe, efficacious, and tolerable to control symptoms of overactive bladder even over the long term. However, it remains unknown if the practical effectiveness of imidafenacin is applicable to ethnic groups other than Japanese.

Comprehensive Health-Related Quality of Life is Influenced by Nocturia and Sleep Disturbance: Investigation Based on the SF-8

“…Intervention with such drugs may be useful for reducing nighttime voiding and several anticholinergic agents are currently available in Japan. Imidafenacin was released in Japan in 2007 [20,21]. It is more bladder-selective compared with other drugs [22], leading to mild anticholinergic adverse effects such as dry mouth and constipation [23], along with good long-term (52 weeks) efficacy, safety, and tolerability [24,25] in OAB patients.…”

A multicenter real-life study of the efficacy of an alpha-blocker with or without anticholinergic agent (imidafenacin) treatment in patients with lower urinary tract symptoms/benign prostatic hyperplasia and storage symptoms

“…19 In addition, the elimination half-life of imidafenacin (3.0 hours) is shorter than the elimination half-lives of other antimuscarinic agents. 21 The results from these studies have provided evidence that supports the efficacy, safety, and tolerability of imidafenacin in male LUTS patients with storage symptoms. In an effort to reduce storage symptoms without the severe AEs associated with anticholinergic agents and to compare studies of combination therapy involving low-dose anticholinergic agents, Bae et al, 9 and Kim et al 22 undertook studies and the results showed that combination therapy comprising low-dose propiverine improved the total IPSS and the storage symptom score, 9 and that compared with the standard dose, combination therapy comprising low-dose tolterodine had similar efficacy and safety profiles.…”

“…Furthermore, imidafenacin displays greater selectivity for bladder tissue compared with salivary gland tissue . In addition, the elimination half‐life of imidafenacin (3.0 hours) is shorter than the elimination half‐lives of other antimuscarinic agents . The results from these studies have provided evidence that supports the efficacy, safety, and tolerability of imidafenacin in male LUTS patients with storage symptoms.…”

Cognitive Safety and Overall Tolerability of Imidafenacin in Clinical Use: A Long‐Term, Open‐Label, Post‐Marketing Surveillance Study

“…To confirm the efficacy of a particular drug, a study should determine whether the therapeutic agent is superior to a placebo and whether it is also not inferior to a pre‐existing drug. However, imidafenacin has already been reported to have significantly higher efficacy than placebos in both phase 2 and 3 trials,and these findings have been well‐reviewed …”