FDA

Trospium Chloride

Approved 17 Nov 2010OralTablet

The FDA lists this product in 12 strengths and forms.

Indications

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. 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 )

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. 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 )

Warnings and precautions

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 Tablets should be used only with careful monitoring. ( 5.4 )
Central Nervous System Effects: Somnolence has been reported with Trospium Chloride Tablets. Advise patients not to drive or operate heavy machinery until they know how Trospium Chloride Tablets affect 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 )

5.1Risk 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) ].

At a glance

Brand name: Trospium Chloride
Route: Oral
Dosage form: Tablet
Applicant: Padagis US
Status: Prescription
FDA approval: 17 Nov 2010
Application: ANDA091573-001

Indications

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. 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 )

Warnings and precautions

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 Tablets should be used only with careful monitoring. ( 5.4 )
Central Nervous System Effects: Somnolence has been reported with Trospium Chloride Tablets. Advise patients not to drive or operate heavy machinery until they know how Trospium Chloride Tablets affect 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 )

5.1Risk 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) ].

Pregnancy and breastfeeding

8.1Pregnancy Teratogenic Effects Pregnancy Category C:

There are no adequate and well-controlled studies of Trospium Chloride Tablets in pregnant women. Trospium Chloride Tablets 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 Tablets 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.

Adverse reactions

The most common adverse reactions (≥ 1%) with Trospium Chloride Tablets are dry mouth (20.1%), constipation (9.6%), and headache (4.2%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Perrigo at 1-800-328-5113 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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 Tablets was evaluated in controlled clinical trials in a total of 2975 patients, who were treated with Trospium Chloride Tablets (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 Tablets 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 Tablets 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 Tablets 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 Tablets, reported in ≥ 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 ≥ 0.5% and < 1.0% of Trospium Chloride Tablets treated patients, and more common with Trospium Chloride Tablets 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.

6.2Post-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.

Trospium Chloride

Indications

Contraindications

Warnings and precautions

5.1Risk of Urinary Retention Trospium Chloride

At a glance

Two medicines in one question?

Trospium Chloride

Indications

Contraindications

Warnings and precautions

5.1Risk of Urinary Retention Trospium Chloride

At a glance

Two medicines in one question?

5.3Decreased Gastrointestinal Motility Trospium Chloride

5.4Controlled Narrow-angle Glaucoma

5.5Central Nervous System Effects Trospium Chloride

5.6Anticholinergic Adverse Reactions in Patients with Moderate Renal Impairment

Interactions

7.1Digoxin

7.2Drugs Eliminated by Active Tubular Secretion

7.3Antimuscarinic Agents

Pregnancy and breastfeeding

8.1Pregnancy Teratogenic Effects Pregnancy Category C:

Adverse reactions

6.1Clinical Trials Experience

6.2Post-marketing Experience

Composition

Strengths and forms

Official product information