DOSAGE & ADMINISTRATION SECTION

Highlight: • The recommended dosage of Trospium Chloride Extended-Release Capsules is one 60 mg capsule daily in the morning. Trospium Chloride Extended-Release Capsules should be dosed with water on an empty stomach, at least one hour before a meal. (2)

•Trospium Chloride Extended-Release Capsules are not recommended for use in patients with severe renal impairment (creatinine clearance less than 30 mL/minute). (2)

2 DOSAGE AND ADMINISTRATION

The recommended dosage of Trospium Chloride Extended-Release Capsules is one 60 mg capsule daily in the morning. Trospium Chloride Extended-Release Capsules should be dosed with water on an empty stomach, at least one hour before a meal.

Trospium Chloride Extended-Release Capsules are not recommended for use in patients with severe renal impairment (creatinine clearance less than 30 mL/minute) [see Warnings and Precautions (5.6), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3)].

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WARNINGS AND PRECAUTIONS SECTION

Highlight: • Trospium Chloride Extended-Release Capsules should be administered with caution to patients with clinically significant bladder outflow obstruction or gastrointestinal obstructive disorders due to risk of urinary or gastric retention. ( 5.1, 5.3)

• Angioedema of the face, lips, tongue and/or larynx has been reported with trospium chloride. ( 5.2)

• In patients with narrow angle glaucoma, Trospium Chloride Extended-Release Capsules should be used only with careful monitoring. ( 5.4)

• Central Nervous System Effects: Somnolence has been reported with Trospium Chloride Extended-Release Capsules. Advise patients not to drive or operate heavy machinery until they know how Trospium Chloride Extended-Release Capsules affects them. ( 5.5)

• Trospium Chloride Extended-Release Capsules are not recommended for use in patients with severe renal impairment (creatinine clearance less than 30 mL/minute). ( 5.6)

• Alcohol should not be consumed within 2 hours of Trospium Chloride Extended- Release Capsules administration. ( 5.7)

5 WARNINGS AND PRECAUTIONS

5.1 Risk of Urinary Retention

Trospium Chloride Extended-Release Capsules should be administered with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention [see contraindications ( 4)].

5.2 Angioedema

Angioedema of the face, lips, tongue and/or larynx has been reported with trospium chloride. In one case, angioedema occurred after the first dose of trospium chloride. Angioedema associated with upper airway swelling may be life threatening. If involvement of the tongue, hypopharynx, or larynx occurs, trospium chloride should be promptly discontinued and appropriate therapy and/or measures necessary to ensure a patent airway should be promptly provided.

5.3 Decreased Gastrointestinal Motility

Trospium Chloride Extended-Release Capsules should be administered with caution to patients with gastrointestinal obstructive disorders because of the risk of gastric retention [ see Contraindications (4)]. Trospium Chloride Extended-Release Capsules, like other antimuscarinic agents, may decrease gastrointestinal motility and should be used with caution in patients with conditions such as ulcerative colitis, intestinal atony and myasthenia gravis.

5.4 Controlled Narrow-angle Glaucoma

In patients being treated for narrow-angle glaucoma,Trospium Chloride Extended-Release Capsules should only be used if the potential benefits outweigh the risks, and in that circumstance only with careful monitoring [see Contraindications (4)].

5.5 Central Nervous System Effects

Trospium Chloride Extended-Release and Trospium Chloride Immediate Release Capsules are associated with anticholinergic central nervous system (CNS) effects [see Adverse Reactions (6.2 )]. A variety of CNS anticholinergic effects have been reported, including dizziness, confusion, hallucinations and somnolence. Patients should be monitored for signs of anticholinergic CNS effects, particularly after beginning treatment or increasing the dose. Advise patients not to drive or operate heavy machinery until they know how Trospium Chloride Extended-Release Capsules affects them. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered.

5.6 Patients with Severe Renal Impairment

Trospium Chloride Extended-Release Capsules are not recommended for use in patients with severe renal impairment (creatinine clearance less than 30 mL/minute) [see Dosage and Administration (2), Use in Specific Populations (8.6), and Clinical Pharmacology (12.3 )].

5.7 Alcohol Interaction

Alcohol should not be consumed within 2 hours of Trospium Chloride Extended- Release Capsules administration. In addition, patients should be informed that alcohol may enhance the drowsiness caused by anticholinergic agents.

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DRUG INTERACTIONS SECTION

Highlight: • 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 DRUG INTERACTIONS

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, 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.

7.1 Digoxin

Concomitant use of trospium chloride 20mg 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 )].

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NONCLINICAL TOXICOLOGY SECTION

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis: Carcinogenicity studies with trospium chloride 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 1 and 16 times, respectively (based on AUC), the expected clinical exposure levels at the maximum recommended human dose (MRHD) of 60 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 mouse 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).

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INFORMATION FOR PATIENTS SECTION

17 PATIENT COUNSELING INFORMATION

"See FDA-Approved Patient labeling (Patient Information)"

17.1 Angioedema

Patients should be informed that Trospium Chloride Extended-Release Capsules may produce angioedema which could result in life-threatening airway obstruction. Patients should be advised to promptly discontinue Trospium Chloride Extended-Release Capsules therapy and seek immediate medical attention if they experience edema of the tongue, edema of the laryngopharynx, or difficulty breathing.

17.2 When Not to Use

Prior to treatment, patients should fully understand the risks and benefits of Trospium Chloride Extended-Release Capsules. In particular, patients should be informed not to take Trospium Chloride Extended-Release Capsules if they:

• have urinary retention;

• gastric retention;

• uncontrolled narrow-angle glaucoma;

• are allergic to any component of Trospium Chloride Extended-Release Capsules

17.3 Administration

Patients should be instructed regarding the recommended dosing and administration of Trospium Chloride Extended-Release Capsules:

• Take one Trospium Chloride Extended-Release Capsule daily in the morning with water.

• Take Trospium Chloride Extended-Release Capsules on an empty stomach or at least 1 hour before a meal.

• Use of alcoholic beverages within 2 hours of dosing with Trospium Chloride Extended-Release Capsules is not recommended.

17.4 Adverse Reactions

Patients should be informed that the most common side effects with Trospium Chloride Extended-Release Capsules are dry mouth and constipation and that other less common side effects include trouble emptying the bladder, blurred vision, and heat prostration. Because anticholinergics, such as Trospium Chloride Extended-Release Capsules , may produce dizziness or blurred vision, patients should be advised to exercise caution in decisions to engage in potentially dangerous activities until the drug’s effects have been determined. Patients should be informed that alcohol may enhance the drowsiness caused by anticholinergic agents.

• Listed trademarks are the property of their respective owners.

Manufactured For:
Burel Pharmaceuticals, Inc.
Brandon, MS 39042

Manufactured By:
Granules Pharmaceuticals Inc.
Chantilly, VA 20151

Rev. 02/2021

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