Trospium Chloride

Mechanism of Action

Reduces the smooth muscle tone of the bladder by antagonizing the effects of acetyl choline on muscarinic receptors.

Pharmacokinetics

Absorption: <10%; reduced when administered with high-fat meal

Half-life: 20 hr (immediate release)

Peak plasma time: 5-6 hr

Protein bound: 45-85%

Metabolism: Not fully elucidated; major pathway is thought to be ester hydrolysis followed by glucuronide conjugation of benzylic acid

Renal clearance: 29.07 L/hr

Excretion: Feces (85.2%); urine (5.8% with 60% unchanged drug)

Trospium Chloride tablets are contraindicated in patients with:

• urinary retention
• gastric retention
• uncontrolled narrow-angle glaucoma.
• known hypersensitivity to the drug or its ingredients. Angioedema, rash and anaphylactic reaction have been reported.

7.1 Digoxin

Concomitant use of Trospium Chloride tablets and digoxin did not affect the pharmacokinetics of either drug [see Clinical Pharmacology (12.3)].

7.2 Drugs Eliminated by Active Tubular Secretion

Although demonstrated in a drug-drug interaction study not to affect the pharmacokinetics of digoxin, Trospium Chloride tablets have the potential for pharmacokinetic interactions with other drugs that are eliminated by active tubular secretion (e.g., procainamide, pancuronium, morphine, vancomycin, and tenofovir). Co-administration of Trospium Chloride tablets with these drugs may increase the serum concentration of Trospium Chloride tablets and/or the coadministered drug due to competition for this elimination pathway. Careful patient monitoring is recommended in patients receiving such drugs [see Clinical Pharmacology (12.3)].

Antimuscarinic Agents

The concomitant use of Trospium Chloride tablets with other antimuscarinic agents that produce dry mouth, constipation, and other anticholinergic pharmacological effects may increase the frequency and/or severity of such effects. Trospium Chloride tablets may potentially alter the absorption of some concomitantly administered drugs due to anticholinergic effects on gastrointestinal motility.

Metformin

Co-administration of 500 mg metformin immediate release tablets twice daily with Trospium Chloride 60 mg extended release tablets reduced the steady-state systemic exposure of trospium by approximately 29% for mean AUC0-24 and by 34% for mean Cmax [see Clinical Pharmacology (12.3)].

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Carcinogenicity studies with Trospium Chloride tablets were conducted in mice and rats for 78 weeks and 104 weeks, respectively, at maximally tolerated doses. No evidence of a carcinogenic effect was found in either mice or rats administered up to 200 mg/kg/day, approximately 9 times the expected clinical exposure levels at the maximum recommended human dose (MRHD) of 40 mg.  

Mutagenesis

Trospium Chloride was not mutagenic nor genotoxic in tests in vitro in bacteria (Ames test) and mammalian cells (L5178Y mouse lymphoma and CHO cells) or in vivo in the rat micronucleus test. 

Impairment of Fertility

No evidence of impaired fertility was observed in rats administered doses up to 200 mg/kg/day (about 16 times the expected clinical exposure at the MRHD, based on AUC).

Trospium Chloride tablets, USP 20 mg (brownish-yellow, round, biconvex, film-coated tablets, engraved “APO” on one side and “TR” over “20” on the other side) are supplied as follows:

Bottles of 60       NDC 60505-3454-6

Bottles of 500     NDC 60505-3454-5

Bottles of 1000   NDC 60505-3454-8

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].