Trospium chloride extended-release

Trospium is metabolized by ester hydrolysis and excreted by the kidneys through a combination of tubular secretion and glomerular filtration. Based on in vitro data, no clinically relevant metabolic drug-drug interactions are anticipated with Trospium Chloride Extended-Release Capsules. However, some drugs which are actively secreted by the kidney may interact with Trospium Chloride Extended-Release Capsules by competing for renal tubular secretion. The concomitant use of Trospium Chloride Extended-Release Capsules with other antimuscarinic agents that produce dry mouth and constipation and other anticholinergic effects may increase the frequency and/or severity of such effects.

Trospium Chloride Extended-Release Capsules may potentially alter the absorption of some concomitantly administered drugs due to anticholinergic effects on gastrointestinal motility. • Some drugs which are actively secreted by the kidney may interact with Trospium Chloride Extended-Release Capsules by competing for renal tubular secretion. ( 7 ) • Concomitant use with digoxin did not affect the pharmacokinetics of either drug. ( 7.1 ) • Exposure to trospium on average was comparable in the presence of and without antacid, however, some individuals demonstrated increases or decreases in trospium exposure in the presence of antacid. The clinical relevance of these findings is not known.

( 7.2 ) • Concomitant use with metformin immediate release tablets reduced exposure and peak concentration of trospium. ( 7.3 )

7.1 Digoxin Concomitant use of trospium chloride 20 mg twice daily and digoxin did not affect the pharmacokinetics of either drug [ see CLINICAL PHARMACOLOGY (12.3) ].

7.2 Antacid While the systemic exposure of trospium on average was comparable with and without antacid containing aluminum hydroxide and magnesium carbonate, 5 out of 11 individuals in a drug interaction study demonstrated either an increase or decrease in trospium exposure, in presence of antacid. The clinical relevance of these findings is not known [ see CLINICAL PHARMACOLOGY (12.3) ].

7.3 Metformin Co-administration of 500 mg metformin immediate-release tablets twice daily reduced the steady-state systemic exposure of trospium by approximately 29% for mean AUC (0-24) and by 34% for mean C max . The effect of a decrease in trospium exposure on the efficacy of Trospium Chloride Extended-Release Capsules is unknown. The steady-state pharmacokinetics of metformin were comparable when administered with or without 60 mg Trospium Chloride Extended-Release Capsules once daily under fasted condition. The effect of metformin at higher doses on trospium PK is unknown [ see CLINICAL PHARMACOLOGY (12.3) ].

8.1 Pregnancy Teratogenic Effects Pregnancy Category C: There are no adequate and well-controlled studies of Trospium Chloride Extended-Release Capsules in pregnant women. Trospium Chloride Extended-Release Capsules should be used during pregnancy only if the potential benefit to the patient outweighs the risk to the patient and fetus. Women who become pregnant during Trospium Chloride Extended-Release Capsules treatment are encouraged to contact their physician. Trospium chloride was not teratogenic at statistically significant levels in rats or rabbits administered doses up to 200 mg/kg/day.

This corresponds to systemic exposures up to approximately 16 and 32 times, respectively (based on AUC), the clinical exposure at the maximum recommended human dose (MRHD) of 60 mg. However, in rabbits, one fetus in each of the three treated dose groups (1, 1, and 32 times the MRHD) demonstrated multiple malformations, including umbilical hernia and skeletal malformations. A no effect level for maternal and fetal toxicity was observed at levels approximately equivalent to the clinical exposure at the MRHD (20 mg/kg/day in rats and rabbits). No developmental toxicity was observed in the offspring of female rats exposed pre- and post-natally to up to 200 mg/kg/day.

8.3 Nursing Mothers Trospium chloride (2 mg/kg orally and 50 mcg/kg intravenously) was excreted, to a limited extent (< 1%), into the milk of lactating rats (primarily as parent compound). It is not known whether this drug is excreted into human milk. Because many drugs are excreted into human milk, Trospium Chloride Extended-Release Capsules should be used during lactation only if the potential benefit justifies the potential risk.