Trospium
Quaternary anticholinergic for overactive bladder
Trospium is an anticholinergic of the quaternary ammonium type that has been available in Germany since 1991 for the treatment of overactive bladder and detrusor hyperreflexia. Brand names include Spasmex, Spasmo Urgenin Neo and Spasmo Lyt, and generics are widely available. The compound is one of the oldest muscarinic receptor antagonists still in common use for bladder relaxation and is notable for particularly low penetration into the cerebrospinal fluid.
The distinctive chemical structure with a permanent positive charge on the quaternary nitrogen prevents the molecule from crossing the blood brain barrier. This makes trospium, compared with tertiary anticholinergics such as oxybutynin, particularly attractive for elderly patients who are sensitive to central anticholinergic side effects such as confusion, delirium or memory impairment. The Priscus list regards trospium as a manageable alternative for elderly patients.
Mechanism of Action
Trospium competitively blocks muscarinic acetylcholine receptors of the M3 subtype on the smooth muscle of the urinary bladder. Acetylcholine is released from parasympathetic nerve endings and triggers contraction of the detrusor vesicae via M3. Blockade prevents unintended contractions, increases bladder capacity and prolongs the interval between voids.
The compound also binds M1 and M2 receptors in other organs, which can cause typical peripheral anticholinergic side effects (dry mouth, constipation, accommodation disturbance, tachycardia). Owing to poor CNS penetration, central effects such as drowsiness, confusion or hallucinations are considerably less frequent than with oxybutynin or tolterodine.
Oral bioavailability is only about 10 percent; the compound is hydrophilic and largely excreted unchanged renally. The half life is about 18 hours. Administration on an empty stomach is important because food further reduces the already low absorption. Administration is recommended at least one hour before or two hours after a meal.
Indications
- Overactive bladder with urge incontinence in adults
- Pollakisuria and imperative urinary urgency without identifiable organic cause
- Detrusor hyperreflexia in neurogenic bladder dysfunction (multiple sclerosis, spinal cord injury, Parkinson disease)
- Mixed urinary incontinence with a dominant urge component
- Postoperative irritable bladder after urological procedures
Dosage and Administration
Standard dose: 15 mg three times daily or 20 mg twice daily. Sustained release formulations: 60 mg once daily. The choice of formulation depends on tolerability and convenience; therapeutic efficacy is comparable.
Administration should be one hour before a meal or at least two hours afterwards. Tablets should be swallowed whole with a glass of water. If a dose is missed, take the next dose as planned; do not double up.
Renal impairment: for eGFR 10 to 30 ml/min, 15 mg once daily or every other day. Contraindicated at eGFR below 10 ml/min. Hepatic impairment: no formal dose adjustment because of predominantly renal elimination. Elderly patients: cautious titration, although trospium is better tolerated than other anticholinergics.
Side Effects
Very common and common: dry mouth (considerably more frequent than other symptoms), constipation, dyspepsia, nausea, headache, blurred vision, accommodation disturbance, tachycardia, urinary retention in predisposed patients.
Uncommon: abdominal pain, diarrhoea, flatulence, rash, pruritus, urinary tract infections; rhabdomyolysis has been reported in severe renal impairment.
Rare: anaphylactic reactions, angioedema, precipitation of narrow angle glaucoma, voiding dysfunction up to urinary retention, gastrointestinal motility disturbances; in isolated cases central effects in patients with a compromised blood brain barrier (confusion, delirium).
Particularity in elderly patients: even with low CNS penetration, an anticholinergic delirium can occur under a high cumulative anticholinergic burden in polypharmacy. The summation of multiple substances with anticholinergic activity (trospium plus promethazine plus amitriptyline) is the main risk, not trospium alone.
Interactions
- Other anticholinergics (biperiden, amitriptyline, promethazine, scopolamine): additive anticholinergic side effects; consider total burden
- Parasympathomimetics (pilocarpine, carbachol): mutual attenuation of effect
- Antacids containing aluminium or magnesium: reduce trospium absorption; keep a 2 hour interval
- Substances using active tubular secretion (metformin, procainamide, digoxin): theoretical competition for renal excretion, usually not clinically relevant
- Substances with motility inhibition (opioids, loperamide): additive constipation
- Proton pump inhibitors, H2 blockers: changes in gastric pH may slightly affect absorption
Special Notes
Contraindications: narrow angle glaucoma, myasthenia gravis, severe ulcerative colitis, toxic megacolon, mechanical urinary outflow obstruction (bladder neck obstruction), tachyarrhythmias, severe renal impairment (eGFR below 10 ml/min), known hypersensitivity.
Voiding diary: a voiding diary over at least three days before starting therapy is useful. It documents voiding frequency, volume and continence, allows assessment of treatment success and helps rule out overactivity from mechanical causes.
Combination with pelvic floor training: pharmacological therapy does not replace physiotherapy. Pelvic floor training, bladder training and a scheduled toileting plan remain pillars of the non pharmacological basic therapy. Their combination with trospium is more effective than any single measure.
Pregnancy: experience is limited, use only when clearly indicated. Breastfeeding: not recommended, transfer into breast milk is not reliably quantified. Children and adolescents under 18 years: not approved.
Monitoring: voiding diary, post void residual volume after 4 weeks, creatinine and electrolytes in renal impairment. Evaluate treatment success after 8 weeks; if the response is inadequate consider switching to mirabegron or another anticholinergic.
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Frequently Asked Questions
Why should I take trospium on an empty stomach?
The bioavailability of trospium is already low at 10 percent, and food further reduces absorption. Taking it one hour before or two hours after a meal ensures more reliable plasma concentrations and better efficacy. Consistent dosing at the same time each day is important.
Why is trospium suitable for elderly patients?
As a quaternary ammonium compound, trospium hardly crosses the blood brain barrier, so central anticholinergic effects such as confusion, delirium or memory impairment are much less frequent than with oxybutynin or tolterodine. The Priscus list lists trospium as a manageable option in geriatrics.
How quickly does trospium work?
An improvement in urinary urgency is often noticeable after the first week, whereas the full effect on voiding frequency and incontinence appears after 4 to 8 weeks. Efficacy assessment with a voiding diary after 8 weeks is standard; consider switching if there is no improvement.
Do I still need to do pelvic floor training?
Yes, absolutely. Medication only suppresses involuntary urinary urgency; it does not strengthen the sphincters. Pelvic floor training, bladder training and behavioural adjustments are essential components of therapy and act synergistically with the medication. The combination is more effective than any single measure.
Sources
- EMA, European Medicines Agency
- AWMF, S2k guideline on urinary incontinence in women and men
- Gelbe Liste, trospium drug profile
- BfArM, Federal Institute for Drugs and Medical Devices
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