Tolterodine

Danger

H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]

P203, P264, P270, P280, P301+P316, P318, P321, P330, P405, and P501 (click each P-code to see the statement)

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

In multiple randomized controlled trials of tolterodine in patients with overactive bladder syndrome, serum aminotransferase and alkaline phosphatase elevations were not common, arising in less than 1% of treated subjects and in a similar proportion of placebo recipients. In these clinical trials there were no reports of clinically apparent liver injury or jaundice. Since the approval of tolterodine in 1998 and its widescale use (with more than 1 million prescriptions filled yearly in the United States), there has been only one published case report of liver injury with symptoms and jaundice attributed to its use (Case 1). Thus, acute symptomatic liver injury due to tolterodine must be very rare, if it occurs at all.

To prevent toxicity, patients with hepatic impairment should be given a lower dose since the drug's elimination is lower than that of healthy patients. Additionally, tolterodine demonstrated higher concentrations in patients with renal impairment. Therefore, recommendations include a decrease in drug dosage in both patients with hepatic or renal impairment.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

tolterodine

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

G04BD07

G - Genito urinary system and sex hormones

QG - Genito urinary system and sex hormones

Tolterodine is a competitive muscarinic receptor antagonist. Both urinary bladder contraction and salivation are mediated via cholinergic muscarinic receptors. After oral administration, tolterodine is metabolized in the liver, resulting in the formation of the 5-hydroxymethyl derivative, a major pharmacologically active metabolite. The 5-hydroxymethyl metabolite, which exhibits an antimuscarinic activity similar to that of tolterodine, contributes significantly to the therapeutic effect. Both tolterodine and the 5-hydroxymethyl metabolite exhibit a high specificity for muscarinic receptors, since both show negligible activity or affinity for other neurotransmitter receptors and other potential cellular targets, such as calcium channels. Tolterodine has a pronounced effect on bladder function. The main effects of tolterodine are an increase in residual urine, reflecting an incomplete emptying of the bladder, and a decrease in detrusor pressure, consistent with an antimuscarinic action on the lower urinary tract.

Both tolterodine and its active metabolite, 5-hydroxymethyltolterodine, act as competitive antagonists at muscarinic receptors. This antagonism results in inhibition of bladder contraction, decrease in detrusor pressure, and an incomplete emptying of the bladder.

WHE7A56U7K

TOLTERODINE

Established Pharmacologic Class [EPC] - Cholinergic Muscarinic Antagonist

Mechanisms of Action [MoA] - Cholinergic Muscarinic Antagonists

Tolterodine is a Cholinergic Muscarinic Antagonist. The mechanism of action of tolterodine is as a Cholinergic Muscarinic Antagonist.

TOLTERODINE

Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system.

Drugs used in the treatment of urological conditions and diseases such as URINARY INCONTINENCE and URINARY TRACT INFECTIONS.

Following administration of a 5-mg oral dose of 14C-tolterodine solution to healthy volunteers, 77% of radioactivity was recovered in urine and 17% was recovered in feces in 7 days.

113 ± 26.7 L