Darifenacin

Like most anticholinergic agents, darifenacin has not been linked to liver enzyme elevations during therapy or to instances of clinically apparent liver injury with symptoms or jaundice. In multiple prospective clinical trial of darifenacin in patients with overactive bladder syndrome, ALT elevations were reported in less than 1% of treated subjects, rates similar to that of placebo recipients. Despite widespread clinical use for almost two decades, there have been no published case reports of clinically apparent liver injury convincingly attributed to darifenacin use.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

darifenacin

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

G04BD10

G - Genito urinary system and sex hormones

QG - Genito urinary system and sex hormones

Darifenacin is a competitive muscarinic receptor antagonist. <i>In vitro</i> studies using human recombinant muscarinic receptor subtypes show that darifenacin has greater affinity for the M3 receptor than for the other known muscarinic receptors (9 and 12-fold greater affinity for M3 compared to M1 and M5, respectively, and 59-fold greater affinity for M3 compared to both M2 and M4). Muscarinic receptors play an important role in several major cholinergically mediated functions, including contractions of the urinary bladder smooth muscle and stimulation of salivary secretion. Adverse drug effects such as dry mouth, constipation and abnormal vision may be mediated through effects on M3 receptors in these organs.

Hepatic. Primarily mediated by the cytochrome P450 enzymes CYP2D6 and CYP3A4.

Hepatic. Primarily mediated by the cytochrome P450 enzymes CYP2D6 and CYP3A4. Half Life: The elimination half-life of darifenacin following chronic dosing is approximately 13-19 hours.

APG9819VLM

DARIFENACIN

Established Pharmacologic Class [EPC] - Cholinergic Muscarinic Antagonist

Mechanisms of Action [MoA] - Cholinergic Muscarinic Antagonists