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FDA Approval

Trospium Chloride

FDA-approved pharmaceutical product with comprehensive regulatory information, manufacturing details, and complete labeling documentation.

FDA Approval Summary

Effective Date
April 2, 2024
Labeling Type
HUMAN PRESCRIPTION DRUG LABEL
Trospium(20 mg in 1 1)

Manufacturing Establishments1

FDA-registered manufacturing facilities and establishments involved in the production, packaging, or distribution of this drug product.

Aphena Pharma Solutions - Tennessee, LLC

Aphena Pharma Solutions - Tennessee, LLC

128385585

Products1

Detailed information about drug products covered under this FDA approval, including NDC codes, dosage forms, ingredients, and administration routes.

Trospium Chloride

Product Details

NDC Product Code
71610-812
Application Number
ANDA204945
Marketing Category
ANDA (C73584)
Route of Administration
ORAL
Effective Date
April 2, 2024
HYPROMELLOSE, UNSPECIFIEDInactive
Code: 3NXW29V3WOClass: IACT
BUTYL ALCOHOLInactive
Code: 8PJ61P6TS3Class: IACT
CROSCARMELLOSE SODIUMInactive
Code: M28OL1HH48Class: IACT
MAGNESIUM STEARATEInactive
Code: 70097M6I30Class: IACT
LACTOSE MONOHYDRATEInactive
Code: EWQ57Q8I5XClass: IACT
POVIDONE, UNSPECIFIEDInactive
Code: FZ989GH94EClass: IACT
MICROCRYSTALLINE CELLULOSEInactive
Code: OP1R32D61UClass: IACT
POLYETHYLENE GLYCOL, UNSPECIFIEDInactive
Code: 3WJQ0SDW1AClass: IACT
SHELLACInactive
Code: 46N107B71OClass: IACT
PROPYLENE GLYCOLInactive
Code: 6DC9Q167V3Class: IACT
TALCInactive
Code: 7SEV7J4R1UClass: IACT
TrospiumActive
Code: 1E6682427EClass: ACTIBQuantity: 20 mg in 1 1
SUCROSEInactive
Code: C151H8M554Class: IACT
SILICON DIOXIDEInactive
Code: ETJ7Z6XBU4Class: IACT
FERRIC OXIDE REDInactive
Code: 1K09F3G675Class: IACT
TITANIUM DIOXIDEInactive
Code: 15FIX9V2JPClass: IACT

Drug Labeling Information

Complete FDA-approved labeling information including indications, dosage, warnings, contraindications, and other essential prescribing details.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

PRINCIPAL DISPLAY PANEL - 20mg

NDC 71610-812 - Trospium Chloride, USP 20mg Tablets - Rx Only

Label


RECENT MAJOR CHANGES SECTION

Highlight: Warnings and Precautions, Central Nervous System Effects ( 5.5) 07/2012

RECENT MAJOR CHANGES

Warnings and Precautions, Central Nervous System Effects ( 5.5) 07/2012


DESCRIPTION SECTION

11 DESCRIPTION

Trospium chloride is a quaternary ammonium compound with the chemical name of Spiro [8-azoniabicyclo[3.2.1]octane-8,1'-pyrrolidinium], 3-[(hydroxydiphenylacetyl)oxy]-, chloride, (1α, 3β, 5α). The empirical formula of trospium chloride is C 25H 30ClNO 3and its molecular weight is 427.96. The structural formula of trospium chloride is represented below:

structure

Trospium chloride is a white or almost white, crystalline powder. The compound is very soluble in water.

Each trospium chloride tablet intended for oral administration contains 20 mg of trospium chloride, a muscarinic antagonist, for oral administration. Each trospium chloride tablet also contains the following inactive ingredients: black iron oxide, confectioners' sugar, croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, povidone, propylene glycol, shellac, silicon dioxide, talc and titanium dioxide.

Product meets USP Dissolution Test 2.


INDICATIONS & USAGE SECTION

Highlight: Trospium chloride tablets are a muscarinic antagonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency. ( 1)

1 INDICATIONS AND USAGE

Trospium chloride tablets are a muscarinic antagonist indicated for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency.

DOSAGE & ADMINISTRATION SECTION

Highlight: * The recommended dose of trospium chloride tablet is one 20 mg tablet twice daily. Trospium chloride tablets should be dosed with water on an empty stomach, at least one hour before a meal. ( 2)

  • For patients with severe renal impairment (creatinine clearance less than 30 mL/min), the recommended dose is 20 mg once daily at bedtime. ( 2)
  • In geriatric patients greater than or equal to 75 years of age, dose may be titrated down to 20 mg once daily based upon tolerability. ( 2)

2 DOSAGE AND ADMINISTRATION

The recommended dose is 20 mg twice daily. Trospium chloride tablets should be dosed at least one hour before meals or given on an empty stomach.

Dosage modification is recommended in the following patient populations:

  • For patients with severe renal impairment (creatinine clearance less than 30 mL/min), the recommended dose is 20 mg once daily at bedtime [ see Warnings and Precautions ( 5.5), Use in Specific Populations ( 8.6), and Clinical Pharmacology ( 12.3) ].
  • In geriatric patients greater than or equal to 75 years of age, dose may be titrated down to 20 mg once daily based upon tolerability [ see Use in Specific Populations ( 8.5) ].

DOSAGE FORMS & STRENGTHS SECTION

Highlight: * 20 mg tablets. ( 3)

3 DOSAGE FORMS AND STRENGTHS

Trospium chloride tablets are supplied as 20 mg tablets (round, white to off white, film coated tablets. Imprinted "HP" with black ink on one side and "530" on the reverse side).


CONTRAINDICATIONS SECTION

Highlight: Trospium chloride tablets are contraindicated in

  • patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma, and in patients who are at risk for these conditions ( 4)
  • patients with known hypersensitivity ( 4)

4 CONTRAINDICATIONS

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.

WARNINGS AND PRECAUTIONS SECTION

Highlight: * Trospium chloride tablets 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 controlled narrow angle glaucoma trospium chloride should be used only with careful monitoring. ( 5.4)
  • Central Nervous System Effects: Somnolence has been reported with trospium chloride. Advise patients not to drive or operate heavy machinery until they know how trospium chloride affects them. ( 5.5)
  • Trospium is substantially excreted by the kidney. The effects of moderate renal impairment on systemic exposure are not known but systemic exposure is likely increased. Therefore, the risk of anticholinergic adverse reactions is expected to be greater in patients with moderate renal impairment. ( 5.6)

5 WARNINGS AND PRECAUTIONS

5.1 Risk of Urinary Retention

Trospium chloride tablets 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, the active ingredient in trospium chloride tablets. 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 should be administered with caution to patients with gastrointestinal obstructive disorders because of the risk of gastric retention [ see Contraindications ( 4) ]. Trospium chloride, 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 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 is 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 affects them. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered.

5.6 Anticholinergic Adverse Reactions in Patients with Moderate Renal

Impairment

Trospium is substantially excreted by the kidney. The effects of moderate renal impairment on systemic exposure are not known but systemic exposure is likely increased. Therefore, anticholinergic adverse reactions (including dry mouth, constipation, dyspepsia, urinary tract infection, and urinary retention) are expected to be greater in patients with moderate renal impairment [ see Dosage and Administration ( 2), and Use in Specific Populations ( 8.6) ].


DRUG INTERACTIONS SECTION

Highlight: * Concomitant use with digoxin did not affect the pharmacokinetics of either drug. ( 7.1)

  • Some drugs which are actively secreted by the kidney may interact with trospium chloride by competing for renal tubular secretion. ( 7.2)
  • Concomitant use with metformin immediate release tablets reduced exposure and peak concentration of trospium. ( 7.4)

7 DRUG INTERACTIONS

7.1 Digoxin

Concomitant use of trospium chloride 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 has the potential for pharmacokinetic interactions with other drugs that are eliminated by active tubular secretion (e.g., procainamide, pancuronium, morphine, vancomycin, and tenofovir). Coadministration of trospium chloride with these drugs may increase the serum concentration of trospium chloride 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) ].

7.3 Antimuscarinic Agents

The concomitant use of trospium chloride 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 may potentially alter the absorption of some concomitantly administered drugs due to anticholinergic effects on gastrointestinal motility.

7.4 Metformin

Co-administration of 500 mg metformin immediate release tablets twice daily with SANCTURA XR ®+(trospium chloride 60 mg extended release capsules) reduced the steady-state systemic exposure of trospium by approximately 29% for mean AUC 0-24and by 34% for mean C max[ see Clinical Pharmacology ( 12.3) ].


USE IN SPECIFIC POPULATIONS SECTION

Highlight: * The safety and effectiveness of trospium chloride in pediatric patients have not been established. ( 8.4)

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Teratogenic Effects

**Pregnancy Category C:**There are no adequate and well-controlled studies of trospium chloride in pregnant women. Trospium chloride 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 treatment are encouraged to contact their physician.

Risk Summary

Based on animal data, trospium chloride is predicted to have a low probability of increased risk of adverse developmental outcomes, above background risk. Adverse developmental findings were not observed to correlate with dose in rats or in rabbits. No increased risk above background was observed in rats and rabbits treated at an exposure approximately equivalent to the maximal recommended human dose (MRHD) of 40 mg.

Animal Data

In a rat embryo/fetal development study, pregnant rats received doses of trospium chloride up to 200 mg/kg/day, from implantation to closure of the fetal hard palate, with maternal systemic exposures corresponding to approximately nine times the exposure of women treated at the MRHD of 40 mg, based on AUC. No malformations or fetal toxicity were observed.

The offspring of female rats exposed orally, pre- and post-natally, to trospium chloride up to 200 mg/kg/day showed no increased developmental toxicity over background in surviving pups. However, maternal toxicity (death, irregular breathing, increased excitability) was observed at 200 mg/kg/day. A no-effect level for maternal and pup toxicity (survival to Day 4) was 20 mg/kg/day, an exposure approximately equivalent to the maximal recommended human dose (MRHD) of 40 mg.

In a rabbit embryo/fetal development study, pregnant rabbits received doses of trospium chloride up to 200 mg/kg/day, from implantation to closure of the fetal hard palate. At 200 mg/kg/day, maternal systemic exposures corresponded to approximately 16 times the exposure of women treated at the MRHD of 40 mg, based on AUC. However, one fetus in each of the three treated dose groups (0.3 to 16 times exposures at the MRHD) demonstrated multiple malformations, including umbilical hernia and skeletal malformations. A maternal no-effect level was set at 20 mg/kg/day, at an exposure approximately equivalent to the maximal recommended human dose (MRHD) of 40 mg, due to clinical signs (reduced feces, hunched posture, diarrhea) observed in a pharmacokinetic study at 200 mg/kg/day.

8.2 Labor and Delivery

The effect of trospium chloride tablets on labor and delivery is unknown.

8.3 Nursing Mothers

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

8.4 Pediatric Use

The safety and effectiveness of trospium chloride in pediatric patients have not been established.

8.5 Geriatric Use

Of the 591 patients with overactive bladder who received treatment with trospium chloride in the two U.S., placebo-controlled, efficacy and safety studies, 249 patients (42%) were 65 years of age and older. Eighty-eight trospium chloride treated patients (15%) were greater than or equal to 75 years of age.

In these 2 studies, the incidence of commonly reported anticholinergic adverse reactions in patients treated with trospium chloride (including dry mouth, constipation, dyspepsia, urinary tract infection, and urinary retention) was higher in patients 75 years of age and older as compared to younger patients. This effect may be related to an enhanced sensitivity to anticholinergic agents in this patient population [ see Clinical Pharmacology ( 12.3) ]. Therefore, based upon tolerability, the dose frequency of trospium chloride may be reduced to 20 mg once daily in patients 75 years of age and older.

8.6 Renal Impairment

Severe renal impairment (creatinine clearance less than 30 mL/minute) significantly altered the disposition of trospium chloride. A 4.2-fold and 1.8-fold increase in mean AUC (0-∞)and C max, respectively, and the appearance of an additional elimination phase with a long half-life (~33 hr) were detected in patients with severe renal impairment compared with nearly age- matched subjects with creatinine clearance equal to or higher than 80 mL/min. The different pharmacokinetic behavior of trospium chloride in patients with severe renal impairment necessitates adjustment of dosage frequency [ see Dosage and Administration ( 2) ]. The pharmacokinetics of trospium have not been studied in patients with creatinine clearance ranging from 30-80 mL/min.

Trospium is known to be substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function.

8.7 Hepatic Impairment

There is no information regarding the effect of severe hepatic impairment on exposure to trospium chloride. In a study of patients with mild and with moderate hepatic impairment, given 40 mg of immediate-release trospium chloride, mean C maxincreased 12% and 63%, respectively, and mean AUC (0-∞)decreased 5% and 15%, respectively, compared to healthy subjects. The clinical significance of these findings is unknown. Caution should be used when administering trospium chloride to patients with moderate and severe hepatic impairment.


ADVERSE REACTIONS SECTION

Highlight: The most common adverse reactions (greater than or equal to 1%) with trospium chloride are dry mouth (20.1%), constipation (9.6%), and headache (4.2%). ( 6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Avet Pharmaceuticals Inc. at 1-866-901-DRUG (3784) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety of trospium chloride was evaluated in controlled clinical trials in a total of 2975 patients, who were treated with trospium chloride (N=1673), placebo (N=1056) or active control medications (N=246). Of this total, 1181 patients participated in two, 12-week, U.S., efficacy and safety studies and a 9-month open-label extension. Of this total, 591 patients received trospium chloride tablets 20 mg twice daily. In all controlled trials combined, 232 and 208 patients received treatment with trospium chloride for at least 24 and 52 weeks, respectively.

In all placebo-controlled trials combined, the incidence of serious adverse events was 2.9% among patients receiving trospium chloride tablets 20 mg twice daily and 1.5% among patients receiving placebo. Table 1 lists adverse reactions from the combined 12-week U.S. safety and efficacy trials were reported by at least 1% of patients, and were reported more frequently in the trospium chloride group than in the placebo group.

The two most common adverse reactions reported by patients receiving trospium chloride tablets 20 mg twice daily were dry mouth and constipation. The single most frequently reported adverse reaction for trospium chloride tablets, dry mouth, occurred in 20.1% of trospium chloride treated patients and 5.8% of patients receiving placebo. In the two U.S. studies, dry mouth led to discontinuation in 1.9% of patients treated with trospium chloride tablets 20 mg twice daily. For the patients who reported dry mouth, most had their first occurrence of the event within the first month of treatment.

Table 1. Incidence (%) of adverse reactions with trospium chloride, reported in greater than or equal to 1% of all patients treated with trospium chloride tablets and more frequent with trospium chloride tablets (20 mg twice daily) than placebo in Studies 1 and 2 combined

Adverse Reaction

Placebo
(N=590)

Trospium Chloride Tablets 20 mg
twice daily
(N=591)

Gastrointestinal Disorders

Dry mouth

34 (5.8)

119 (20.1)

Constipation

27 (4.6)

57 (9.6)

Abdominal pain upper

7 (1.2)

9 (1.5)

Constipation aggravated

5 (0.8)

8 (1.4)

Dyspepsia

2 (0.3)

7 (1.2)

Flatulence

5 (0.8)

7 (1.2)

Nervous System Disorders

Headache

12 (2.0)

25 (4.2)

General Disorders

Fatigue

8 (1.4)

11 (1.9)

Renal and Urinary Disorders

Urinary retention

2 (0.3)

7 (1.2)

Eye Disorders

Dry eyes

2 (0.3)

7 (1.2)

Other adverse reactions from the U.S., placebo-controlled trials, occurring in greater than or equal to 0.5% and less than 1.0% of patients treated with trospium chloride, and more common with trospium chloride than placebo are: tachycardia, vision blurred, abdominal distension, vomiting, dysgeusia, dry throat, and dry skin.

During controlled clinical studies, one adverse reaction of angioneurotic edema was reported.

6.2 Post-marketing Experience

The following adverse reactions have been identified during post-approval use of trospium chloride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Gastrointestinal – gastritis; Cardiovascular – palpitations, supraventricular tachycardia, chest pain, syncope, "hypertensive crisis"; Immunological – Stevens-Johnson syndrome, anaphylactic reaction, angioedema; Nervous System – dizziness, confusion, vision abnormal, hallucinations, somnolence and delirium; Musculoskeletal – rhabdomyolysis; General – rash.


OVERDOSAGE SECTION

10 OVERDOSAGE

Overdosage with antimuscarinic agents, including trospium chloride, can result in severe antimuscarinic effects. Supportive treatment should be provided according to symptoms. In the event of overdosage, electrocardiographic monitoring is recommended.

A 7-month-old baby experienced tachycardia and mydriasis after administration of a single dose of trospium 10 mg given by a sibling. The baby's weight was reported as 5 kg. Following admission into the hospital and about 1 hour after ingestion of the trospium, medicinal charcoal was administered for detoxification. While hospitalized, the baby experienced mydriasis and tachycardia up to 230 beats per minute. Therapeutic intervention was not deemed necessary. The baby was discharged as completely recovered the following day.


HOW SUPPLIED SECTION

16 HOW SUPPLIED/STORAGE AND HANDLING

Trospium Chloride Tablets USP, 20 mg intended for oral administration are round, white to off-white, film coated tablets. Imprinted "HP" with black ink on one side and "530" on the reverse side. They are supplied as follows:

Bottle of 60 tablets, NDC 0904-7059-52

Store at 20 oto 25 oC (68 oto 77 oF) [see USP Controlled Room Temperature].

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. Keep container tightly closed


SPL UNCLASSIFIED SECTION

REPACKAGING INFORMATION

Please reference the HOW SUPPLIED section listed above for a description of individual drug products listed below. This drug product has been received by Aphena Pharma Solutions - Tennessee, LLC in a manufacturer or distributor packaged configuration and repackaged in full compliance with all applicable cGMP regulations. The package configurations available from Aphena are listed below:

20mg

NDC 71610-812-87, Bottles of 2400 Tablets

Store between 20°-25°C (68°-77°F). See USP Controlled Room Temperature. Dispense in a tight light-resistant container as defined by USP. Keep this and all drugs out of the reach of children.

Repackaged by:

Aphena

Cookeville, TN 38506

20240402AMH


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