Cizolirtine Citrate

With the ageing population, lower urinary tract symptoms are becoming more prevalent with an estimate that by 2025, 52 million adults in the USA will be affected. After lifestyle modifications fail to resolve symptoms, second-line therapy with medications is often recommended by both the European Association of Urology and the American Urological Association. Considering the vulnerability of older patients to co-morbidities, physicians must be more aware of adverse side effects. This study aims to identify a linkage between common overactive bladder and interstitial cystitis medication and adverse ocular symptoms.

A comprehensive literature search was conducted in MEDLINE, EMBASE, CINAHL, PsycInfo, and HealthSTAR alongside a grey literature search in clinicaltrials.gov to include all articles relating to bladder medication and vision-threatening loss. Covidence review software was utilised to conduct the systematic review.

In total, 222 articles were screened, and 23 articles met the inclusion criteria. Comprehensive coverage of 10 available medications was analysed. All medications reported adverse vision effects stratified over 15 categories. The most common adverse effect was reported to be blurred vision (n = 12 studies). Mirabegron had the most number of adverse types of ocular symptoms that covered 6 categories. Cizolirthine Citrate and Elocatitol had the least amount of ocular side effects reported. From the total of 8459 patients that were treated for either overactive bladder syndrome or interstitial cystitis with oral medications, 422 reported adverse vision effects.

This review suggests that ocular safety should be assessed in patients requiring systematic drug therapy in order to guide future research, focussing on long-term tolerability.

Cizolirtine, a substance-P and calcitonin gene-related peptide release modulator developed for the treatment of pain and urinary incontinence, was orally administered for 26-weeks to rats at dosages of 20, 60 and 200 mg/kg/day. Clinical signs were limited to post-dosing salivation and brown staining on head and muzzle. There were slight decreases in bodyweight gain and slight increases in water consumption among cizolirtine-treated animals. Slight increases in plasma alkaline phosphatase activity, and cholesterol and phospholipid concentrations were observed in mid- and/or high-dose animals. Low urinary volume, pH and sodium and potassium outputs were observed after 12-weeks, and low urinary pH, low sodium and high potassium outputs at end of treatment. Increased relative (to bodyweight) liver weight was observed in high-dose animals. Treated males and high-dose females showed a dose-related increase in the incidence and severity of periacinar hepatocytic hypertrophy and midzonal/periacinar hepatocytic fat vacuolization. Increased incidences of hepatic clear cell foci were observed in all cizolirtine-treated male groups and, to a lesser extent, in treated females. Ovaries of treated females showed a dose-dependent increased incidence of absent corpora lutea and, occasionally, follicular cysts. The dosages of 20 and 60 mg/kg/day were considered as the No-Observed-Adverse-Effect Levels for males and females, respectively.