Description of Trospium
Trospium is an oral non-specific antimuscarinic agent. Trospium is indicated for the treatment of overactive bladder (OAB) in adults. Trospium decreases the frequency of bladder contractions, resulting in a reduction in urinary frequency, urgency and incontinence. Trospium is effective in patients with idiopathic or neurogenic detrusor overactivity, with symptoms of overactive bladder improving as early as 1 week following drug initiation.Trospium has been shown to be as effective as oxybutynin for OAB, but with better tolerability in clinical trials (e.g., less dry mouth).The most commonly reported adverse effects of trospium are dry mouth and constipation. Trospium is not a substrate or inhibitor of CYP450 enzymes; interactions due to drug metabolism are not expected. Per guidelines for non-neurogenic OAB, either bladder-specific antimuscarinics (e.g., selective M3 agents) or beta-3 ARs may be used as a second-line to behavioral interventions. When using a bladder-specific antimuscarinic, use of extended-release oral formulations (e.g., trospium ER) are preferred to immediate-release products of the same drug as they may limit side effects such as dry mouth; transdermal therapy (i.e., oxybutynin gels or patches) may also be offered. Patients experiencing intolerance or side effects may respond well to dose reduction or selection of a different bladder-specific antimuscarinic agent. Clinicians may consider combination therapy with an antimuscarinic and beta-3 AR for patients refractory to monotherapy with either an antimuscarinic or beta-3 AR alone.
Mechanism of Action
Trospium is an antispasmodic, competitive antimuscarinic agent used in the treatment of patients with overactive bladder. Trospium chloride antagonizes the effect of acetylcholine on muscarinic receptors in cholinergically innervated organs. Its actions reduce the tonus of smooth muscle in the bladder. Trospium chloride decreases the frequency of voluntary and involuntary detrusor contractions and increases maximum cystometric bladder capacity and volume at first detrusor contraction. Clinically, trospium decreases urinary urgency, frequency, and incontinence. When used at therapeutic doses, trospium chloride has negligible affinity for nicotinic receptors. It is a quaternary amine and does not cross the blood-brain barrier or conjunctiva like oxybutynin, a tertiary amine.
Pharmacokinetics
Trospium is administered orally.Protein binding ranges from 48—85% depending on formulation and assay used; the majority of trospium is distributed in plasma with an apparent mean volume of distribution of 395 liters for a 20 mg dose of the tablets or > 600 liters for a 60 mg dose of the extended-release capsules. Trospium is a quaternary amine and does not readily cross the conjunctiva or the blood-brain barrier.
The metabolic pathway of trospium is not fully established. Of the absorbed dose, metabolites account for approximately 40% of the excreted dose. The major metabolic pathway is hypothesized to be ester hydrolysis and subsequent conjugation of benzylic acid to form azoniaspironortropanol with glucuronic acid. Cytochrome P-450 does not contribute significantly to the elimination of trospium. Trospium is an inhibitor of CYP2D6; however, the inhibition constant is 1000-fold higher than the Cmax that is achieved with the usual oral regimen. Drug interactions via cytochrome P-450 pathways are not expected to be significant for trospium.
After oral administration, 85.2% of the dose is recovered in the feces. Of the proportion of trospium that is absorbed, 60% is excreted unchanged in the urine. Active tubular secretion is a major elimination route for trospium; the mean renal clearance for trospium is 4-fold higher than average glomerular filtration rate. The plasma half-life of trospium following oral administration is approximately 20 hours for the tablets and 35 hours for the extended-release capsules.
•Route-Specific Pharmacokinetics
Oral Route
After oral administration of either the immediate-release tablets or extended-release capsules, less than 10% of the dose is absorbed. Peak plasma concentrations (Cmax) occur between 5—6 hours post-dose. The pharmacokinetics of trospium are not dose dependent; the increase in Cmax for dosage increases of 20—40 mg and 20—60 mg is 3-fold and 4-fold, respectively. However, increases in AUC are dose proportional for single doses of up to 60 mg. Trospium exhibits diurnal variability in drug exposure, with a decrease in Cmax and AUC of up to 59% and 33%, respectively, for evening doses compared to morning doses. Concomitant administration of the immediate-release tablets with a high fat meal results in reduced absorption, with AUC and Cmax values 70—80% lower than those obtained during a fasting state. A 35% reduction in the AUC and a 60% reduction in the Cmax is observed when the extended-release capsules are given with a high-fat meal. It is recommended, therefore, that trospium be administered at least one hour before meals or on an empty stomach.
Generic Name
- Trospium Chloride
- Sanctura
- Antimuscarinic
- Urinary Antispasmodic
- Overactive bladder, With symptoms of urge urinary incontinence, urgency, and urinary frequency: Adult
- Gastrointestinal: Constipation (8.5% to 9.6% ), Xerostomia (10.7% to 20.1% )
- Neurologic: Headache (4.2% )
- Cardiovascular: Hypertensive crisis, Syncope
- Dermatologic: Stevens-Johnson syndrome
- Immunologic: Anaphylaxis
- Musculoskeletal: Rhabdomyolysis
- Psychiatric: Delirium, Hallucinations
- Other: Angioedema
- Oral: Administer with water on an empty stomach, at least one hour before a meal .
- Oral: (Extended-release capsules) Alcohol should not be consumed within 2 hours of administration .
- Oral Tablet: 20 MG
- Oral Capsule, Extended Release: 60 MG
- Important Note: Beers Criteria: Use caution or avoid use as potentially inappropriate in older adults .
- Overactive bladder, With symptoms of urge urinary incontinence, urgency, and urinary frequency: (Immediate-release tablets) 20 mg orally twice daily with water on an empty stomach, at least 1 hour before a meal
- Overactive bladder, With symptoms of urge urinary incontinence, urgency, and urinary frequency: (Extended-release capsules) 60 mg orally once daily in the morning with water on an empty stomach, at least 1 hour before a meal
- Important Note: Beers Criteria: Use caution or avoid use as potentially inappropriate in older adults .
- General Dosage Information: Safety and effectiveness are not established in pediatric patients
- Time to peak concentration: (immediate release and extended release), approximately 5 hrs
- Bioavailability: (immediate release), 9.6% (4% to 16.1%)
- Effect of food: (immediate release), high fat meal lowers AUC and Cmax by 70% to 80%
- Effect of food: (extended release), high fat meal lowers AUC and Cmax by 35% to 60%
