Trospium - Drug Monograph

Introduction

Trospium chloride is an antimuscarinic medication belonging to the class of quaternary ammonium compounds. It is primarily used for the management of overactive bladder (OAB) syndrome, characterized by symptoms of urinary urgency, frequency, and urge incontinence. Unlike tertiary amine antimuscarinics, trospium's quaternary structure limits its ability to cross the blood-brain barrier, potentially reducing central nervous system side effects.

Mechanism of Action

Trospium acts as a competitive antagonist of muscarinic acetylcholine receptors, particularly the M2 and M3 subtypes found in the detrusor muscle of the bladder. By blocking these receptors, trospium inhibits acetylcholine-induced bladder contractions, resulting in:

• Increased bladder capacity
• Decreased detrusor muscle overactivity
• Reduction in urinary urgency and frequency
• Diminished urge incontinence episodes

Its quaternary ammonium structure contributes to its peripheral selectivity and limited central nervous system penetration.

Indications

• Treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and urinary frequency
• Management of neurogenic detrusor overactivity (in some countries)

Dosage and Administration

• Immediate-release: 20 mg twice daily on an empty stomach or at least 1 hour before meals
• Extended-release: 60 mg once daily in the morning on an empty stomach or at least 1 hour before breakfast

• Renal impairment:

- CrCl < 30 mL/min: 20 mg once daily at bedtime (immediate-release) - ESRD: Not recommended

• Hepatic impairment: No specific dosage adjustment recommended
• Geriatric patients: Consider reduced dosage due to increased susceptibility to anticholinergic effects
• Pediatric use: Safety and effectiveness not established

Pharmacokinetics

• Bioavailability: <10%
• Tmax: Immediate-release: 5-6 hours; Extended-release: 4-6 hours
• Food significantly reduces absorption (up to 70-80%)

• Protein binding: 50-85%
• Volume of distribution: 395 ± 145 L
• Limited CNS penetration due to quaternary ammonium structure

• Minimal hepatic metabolism via ester hydrolysis
• Not significantly metabolized by CYP450 enzymes

• Half-life: Immediate-release: 20 hours; Extended-release: 35 hours
• Excretion: Primarily renal (85% as unchanged drug)
• Feces: 6%

Contraindications

• Urinary retention
• Gastric retention
• Uncontrolled narrow-angle glaucoma
• Hypersensitivity to trospium chloride or any component of the formulation
• Myasthenia gravis
• Toxic megacolon

Warnings and Precautions

• Anticholinergic effects: May cause blurred vision, drowsiness, or dizziness
• Heat prostration: Reduced sweating can occur in hot environments
• Angioedema: Rare cases reported, including airway obstruction
• Cognitive effects: Although CNS penetration is limited, elderly patients may experience confusion
• QT prolongation: Use with caution in patients with known QT prolongation
• Renal impairment: Requires dosage adjustment
• Gastrointestinal disorders: May decrease gastrointestinal motility

Drug Interactions

• Other anticholinergic agents: Additive anticholinergic effects
• Metoclopramide: May antagonize gastrointestinal effects
• Drugs that prolong QT interval: Additive risk (e.g., Class IA/III antiarrhythmics)
• Alcohol: May enhance CNS effects
• Digoxin: Trospium may increase digoxin concentrations

• CYP450 inhibitors or inducers
• Warfarin
• Oral contraceptives

Adverse Effects

• Dry mouth (20%)
• Constipation (10%)
• Headache (4%)
• Fatigue (3%)
• Abdominal pain (2%)
• Dyspepsia (2%)
• Flatulence (2%)

• Angioedema
• Anaphylaxis
• QT prolongation
• Urinary retention
• Gastrointestinal obstruction
• Vision changes including cycloplegia

Monitoring Parameters

• Symptom improvement (voiding diary parameters)
• Residual urine volume (in patients at risk for retention)
• Renal function (serum creatinine/CrCl)
• Cognitive function in elderly patients
• Visual acuity changes
• Signs of urinary retention or constipation
• Electrolytes in patients at risk for QT prolongation

Patient Education

• Take on an empty stomach (at least 1 hour before meals)
• Swallow extended-release tablets whole; do not crush or chew
• Maintain adequate fluid intake

• Avoid excessive heat exposure due to reduced sweating capacity
• Use caution when driving or operating machinery until effects are known
• Limit alcohol consumption

• Sugar-free gum or candies may help with dry mouth
• Increase dietary fiber and fluid intake to prevent constipation
• Report any swelling of face, lips, or difficulty breathing immediately

• Worsening urinary symptoms
• Difficulty passing urine
• Severe constipation
• Vision changes
• Signs of allergic reaction

References

1. Drugs.com. Trospium Prescribing Information. 2023 2. Michel MC, et al. Eur Urol. 2018;73(5):741-750 3. Chancellor MB, et al. Rev Urol. 2018;20(1):1-12 4. Clinical Pharmacology [Internet]. Tampa (FL): Elsevier. Trospium monograph 5. Gormley EA, et al. J Urol. 2015;193(5):1572-1580 6. Novara G, et al. Eur Urol. 2008;54(3):543-562 7. FDA Approved Drug Products: Sanctura (trospium chloride) labeling