Trospium Chloride

Approved Indications:

• Overactive Bladder (OAB):
• Indicated for the treatment of symptoms of overactive bladder, including:
• Urinary frequency
• Urgency
• Urge incontinence (involuntary loss of urine)

Off-label/Clinically Accepted Uses:

• Neurogenic Detrusor Overactivity: In select cases of spinal cord injury or multiple sclerosis when first-line treatments are ineffective.
• Nocturia (investigational use): In patients with OAB-associated nocturia unresponsive to other agents.
• Urinary urgency in elderly patients (with caution and close monitoring for anticholinergic side effects).

Adults:

• Immediate-Release Tablets:
• Dose: 20 mg twice daily.
• Administration: Take at least 1 hour before meals or on an empty stomach.
• Extended-Release Capsules:
• Dose: 60 mg once daily in the morning.
• Administration: Take on an empty stomach with water.

Geriatric Patients:

• Same as adult dosing, but initiate cautiously due to increased anticholinergic sensitivity.
• Monitor closely for cognitive and anticholinergic adverse effects.

Renal Impairment (CrCl <30 mL/min):

• IR tablets: Reduce dose to 20 mg once daily.
• ER capsules: Not recommended due to lack of data.

Hepatic Impairment:

• Use with caution in moderate to severe hepatic impairment; consider dose reduction or alternative agents.

Pediatric Use:

• Not recommended under 18 years of age due to lack of established safety and efficacy.

Administration Tips:

• Avoid taking with high-fat meals to prevent reduced absorption.
• Swallow ER capsules whole; do not crush or chew.

Trospium Chloride is a quaternary ammonium compound that acts as a muscarinic receptor antagonist (anticholinergic). It competitively inhibits the action of acetylcholine on M1 and M3 muscarinic receptors in the bladder detrusor muscle. This results in decreased bladder smooth muscle tone, reduced involuntary bladder contractions, increased bladder capacity, and improved urinary continence. Being a quaternary compound, it has low lipophilicity and limited central nervous system (CNS) penetration, which reduces the likelihood of CNS side effects compared to tertiary amine anticholinergics.

• Absorption:
• Poor oral bioavailability (~10%) due to low gastrointestinal absorption.
• Food reduces systemic exposure by 70–80%; administer on an empty stomach.
• Distribution:
• Protein binding ~50%.
• Does not readily cross the blood-brain barrier.
• Metabolism:
• Hepatic metabolism via ester hydrolysis and conjugation.
• Not significantly metabolized by the CYP450 system.
• Elimination:
• Primarily excreted unchanged in urine (~60%).
• Elimination half-life: ~20 hours (IR); ~35 hours (ER).
• Renal clearance is the major route; dosage adjustments are needed in renal impairment.

• Pregnancy:
• FDA Category C (historical):
• Animal studies have shown adverse fetal effects, but adequate studies in humans are lacking.
• Use only if clearly needed and benefits outweigh risks.
• Lactation:
• Unknown whether trospium is excreted in human milk.
• Due to potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or the drug.
• Recommendation:
• Use with caution during pregnancy and breastfeeding; consider alternative agents with more safety data.

• Primary Class: Antimuscarinic agent (Anticholinergic)
• Subclass: Urinary antispasmodic
• Generation: Non-selective, quaternary amine muscarinic antagonist

• Known hypersensitivity to Trospium Chloride or its excipients
• Urinary retention
• Gastric retention or severe decreased gastrointestinal motility
• Uncontrolled narrow-angle glaucoma
• Severe renal impairment (for extended-release formulation)

• CNS Effects: Although CNS penetration is minimal, elderly patients may still experience confusion or hallucinations.
• Renal Impairment: Use with caution; dose adjustment is necessary. ER form not recommended.
• Hepatic Impairment: Increased systemic exposure; monitor closely or consider dose reduction.
• GI Disorders: Worsening of gastric emptying issues or constipation may occur.
• Heat Prostration: Anticholinergics may reduce sweating and lead to heat intolerance or fever.
• Driving and Machinery Use: May cause drowsiness or blurred vision; caution patients accordingly.

Common Adverse Effects:

• Gastrointestinal: Dry mouth, constipation, abdominal pain, dyspepsia
• Neurological: Headache, dizziness, fatigue
• Ocular: Blurred vision
• Urinary: Urinary retention, dysuria

Serious/Rare Adverse Effects:

• Severe allergic reactions (angioedema, rash)
• Hallucinations, confusion (especially in elderly)
• Tachycardia
• Severe constipation or paralytic ileus

Onset and Severity:

• Most side effects are dose-dependent and occur within the first weeks of therapy.
• Many are mild to moderate and resolve with continued use or dose adjustment.

• Anticholinergic agents: Additive effects; avoid concurrent use with other antimuscarinics (e.g., oxybutynin, tolterodine).
• CNS depressants (e.g., benzodiazepines): Increased risk of sedation and confusion.
• Alcohol: May enhance drowsiness and blurred vision.
• Drugs affecting gastrointestinal motility (e.g., metoclopramide): Antagonistic effects; avoid coadministration.
• Organic cation transporter 2 (OCT2) inhibitors: May affect trospium elimination; caution with drugs like ranitidine, metformin.
• Food Interaction: High-fat meals reduce absorption significantly; always administer on an empty stomach.

• Recent Updates:
• No significant FDA or EMA labeling changes in the past 24 months.
• Still considered second-line therapy in updated OAB guidelines after behavioral modification and first-line antimuscarinics (e.g., solifenacin).
• Clinical Guidance:
• Preferred in patients where limited CNS penetration is desired (e.g., elderly).
• Not recommended as first-line in patients with significant renal impairment or those on multiple anticholinergics.

• Tablets and Capsules:
• Store at 20°C to 25°C (68°F to 77°F).
• Excursions permitted between 15°C to 30°C (59°F to 86°F).
• Protect from moisture and light.
• Keep in original container; tightly closed.
• Do not freeze.
• Handling Precautions:
• Keep out of reach of children.
• Discard if expired or discolored.