darifenacin
Regulatory sources consulted
Approved indications
- Overactive bladder with urge urinary incontinence, urgency, and frequency.
Contraindications
Absolute
- Urinary or gastric retention, uncontrolled narrow-angle glaucoma, or hypersensitivity.
Clinical warnings
- Major warning · It may cause severe constipation, urinary retention, reduced gastrointestinal motility, central anticholinergic effects, and angioedema. — FDA/DailyMed, set_id 28ed5b58-46dd-4140-a877-4b422f780a94
Drug interactions
- HighStrong CYP3A4 inhibitors
Mechanism: They substantially increase darifenacin exposure.
Recommendation: Do not exceed 7.5 mg once daily.
FDA/DailyMed, set_id 28ed5b58-46dd-4140-a877-4b422f780a94https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=28ed5b58-46dd-4140-a877-4b422f780a94
- ModerateOther anticholinergics
Mechanism: They increase anticholinergic effects.
Recommendation: Avoid cumulative burden and monitor.
FDA/DailyMed, set_id 28ed5b58-46dd-4140-a877-4b422f780a94https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=28ed5b58-46dd-4140-a877-4b422f780a94
- HighNarrow-therapeutic-index CYP2D6 substrates, such as flecainide, thioridazine, or tricyclic antidepressants
Mechanism: Darifenacin moderately inhibits CYP2D6 and may increase substrate exposure.
Recommendation: Use cautiously and monitor for toxicity; adjust the substrate when appropriate.
FDA/DailyMed, set_id 28ed5b58-46dd-4140-a877-4b422f780a94https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=28ed5b58-46dd-4140-a877-4b422f780a94
Adverse events
Common (≥1%)
Dry mouth · Constipation · Headache · Dry eyes · Dyspepsia
Rare but serious
Urinary retention · Angioedema · Intestinal obstruction
Pregnancy and lactation
Not recommended during pregnancy. During breastfeeding, decide between avoiding the drug or stopping breastfeeding based on benefit and risk.
Recent literature (PubMed)
bladder based on a systematic review and network meta-analysis approach. Pubmed, Embase, Web of Science, and the Cochrane Register of Clinical Trials databases were systematically searched. The search time frame was from database creation to June 2, 2022. Randomized controlled double-blind trials of oral medication for overactive bladder were screened against the protocol's entry criteria. Trials were evaluated for quality using the Cochrane Risk of Bias Assessment Tool, and data were statistically analyzed using Stata 16.0 software. A total of 60 randomized controlled double-blind clinical trials were included involving 50,333 subjects. Solifenacin 10mg was the most effective in mean daily micturitions and incontinence episodes, solifenacin 5/10mg in mean daily urinary urgency episodes and nocturia episodes, fesoterodine 8mg in urgency incontinence episodes/d and oxybutynin 5mg in voided volume/micturition. In terms of safety, solifenacin 5mg, ER-tolterodine 4mg, mirabegron, vibegron and ER-oxybutynin 10mg all showed a better incidence of dry mouth, fesoterodine 4mg, ER-oxybutynin 10mg, tolterodine 2mg, and vibegron in the incidence of constipation. Compared to placebo, imidafenacin 0.1mg showed a significantly increased incidence in hypertension, solifenacin 10mg in urinary tract infection, fesoterodine 4/8mg and darifenacin 15mg in headache. Solifenacin showed better efficacy. For safety, most anticholinergic drugs were more likely to cause dry mouth and constipation, lower doses were better tolerated. The choice of drugs should be tailored to the patient's specific situation to find the best balance between efficacy and safety.
Catheter-related bladder discomfort (CRBD) is a common complication of intraoperative urinary catheterization. Various studies have evaluated the efficacy of different interventions in postoperative CRBD. The present review was performed to assess the efficacy of these interventions. PubMed, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) databases were systematically searched to identify randomized controlled trials (RCTs) investigating the efficacy of different drugs for the prevention of postoperative CRBD. This review evaluated the incidence and severity of CRBD after different interventions at 0, 1, 2, and 6 h postoperatively. Forty-five studies including 31 different drugs were analyzed. Eleven drugs were investigated in more than two RCTs, of which dexmedetomidine, gabapentin, tolterodine, tramadol, ketamine, nefopam, oxybutynin, pregabalin, and pudendal nerve block (PNB) generally showed significantly higher efficacy than controls postoperatively. Solifenacin only showed significant efficacy compared with the control at 0 h, and intravenous lidocaine only showed significant efficacy compared with the control at 6 h. There were insufficient trials to draw conclusions regarding atropine, butylscopolamine, chlorpheniramine, clonidine, darifenacin, diphenhydramine, glycopyrrolate, intravesical bupivacaine, ketamine-haloperidol, pethidine-haloperidol, ketorolac, lidocaine-prilocaine cream, magnesium, hyoscine n-butyl bromide, oxycodone, paracetamol, parecoxib, trospium, resiniferatoxin, or amikacin. However, all but pethidine-haloperidol and chlorpheniramine showed some efficacy at various time points compared with controls. This review suggests that dexmedetomidine, gabapentin, tolterodine, tramadol, ketamine, nefopam, oxybutynin, pregabalin, and PNB are effective in preventing postoperative CRBD. Considering the efficacy and adverse effects of all drugs, dexmedetomidine and gabapentin were ranked best.
Anticholinergics (ACs) are among the most prescribed drugs. Investigating the impaired cognitive domains due to individual ACs usage is associated with controversial findings. The objective of this study was to investigate the effects of individual ACs on different aspects of cognitive function based on clinical trial studies. This systematic review was conducted following the PRISMA statement. A systematic search was performed in Embase, PubMed, Cochrane Library, Scopus, and Web of Science databases. Risk of bias (RoB) was assessed by the Joanna Briggs Institute checklists and the meta-analysis was performed using the CMA software. Out of 3,026 results of searching, 138 studies were included. A total of 38 studies that assess the cognitive impacts of scopolamine were included in the meta-analysis. Included studies reported cognitive effects of scopolamine, mecamylamine, atropine, biperiden, oxybutynin, trihexyphenidyl, benzhexol, and dicyclomine; however, glycopyrrolate, trospium, tolterodine, darifenacin, fesoterodine, tiotropium, and ipratropium were not associated with cognitive decline. Based on the meta-analyses, scopolamine was associated with reduced recognition (SDM -1.84; 95%CI -2.48 to -1.21; p<0.01), immediate recall (SDM -1.82; 95%CI -2.35 to -1.30; p<0.01), matching to sample (SDM -1.76; 95%CI -2.57 to -0.96; p<0.01), delayed recall (SDM -1.54; 95%CI -1.97 to -1.10; p<0.01), complex memory tasks (SDM -1.31; 95%CI -1.78 to -0.84; p<0.01), free recall (SDM -1.18; 95%CI -1.63 to -0.73; p<0.01), cognitive function (SDM -0.95; 95%CI -1.46 to -0.44; p<0.01), attention (SDM -0.85; 95%CI -1.38 to -0.33; p<0.01), and digit span (SDM -0.65; 95%CI -1.21 to -0.10; p=0.02). There was a high RoB in our included study, especially in terms of dealing with possible cofounders. The limitations of this study suggest a need for more well-designed studies with a longer duration of follow-up on this topic to reach more reliable evidence. Os anticolinérgicos (ACs) estão entr
Antimuscarinics are often the first-choice medications used to treat overactive bladder (OAB), a condition that increasingly affects the aging population. However, concerns regarding their potential impact on cognitive function have persisted for more than a decade. This review was conducted to update the literature on the cognitive safety profiles of various antimuscarinics, integrating findings from both recent and earlier studies to present an updated and comprehensive analysis. A search of English-language publications, including electronic databases and gray literature, focused on the cognitive impacts of antimuscarinics, resulting in a review and assessment of diverse studies and their associated outcomes. Oxybutynin requires caution due to potential adverse effects, suggesting a need to consider alternative therapies. Darifenacin, while promising in preserving cognitive function, warrants further investigation for use in dementia patients. Fesoterodine has shown tolerance without cognitive decline in controlled trials. However, Tolterodine and Solifenacin present conflicting evidence regarding cognitive impairment and dementia risk, respectively, necessitating additional research to ascertain their safety profiles. Careful monitoring and treatment of patients taking these medications for cognitive impairment are essential. Further research, particularly in vulnerable populations, is crucial to establish cognitive safety profiles of various antimuscarinics and inform optimal OAB treatment strategies.