Uritol

Approved Indications:

• Overactive Bladder (OAB):
• For the treatment of overactive bladder with symptoms of urinary frequency, urgency, and/or urge incontinence in adults.

Pediatric Use:

• Neurogenic Detrusor Overactivity (NDO):
• In children aged ≥6 years with a body weight ≥25 kg, for the treatment of urinary incontinence due to neurogenic detrusor overactivity.

Off-label or Clinically Accepted Uses:

• Mixed Urinary Incontinence:
• Used in combination with behavioral therapy in some patients.
• Nocturia and Nocturnal Enuresis (select pediatric or elderly patients):
• In select cases, where urgency plays a role, under specialist supervision.

Adults:

• Oral Immediate-Release Tablet:
• 2 mg twice daily. May be reduced to 1 mg twice daily in case of hepatic impairment or tolerability concerns.
• Oral Extended-Release Capsule (Tolterodine ER):
• 4 mg once daily. Dose may be reduced to 2 mg once daily in case of hepatic or renal impairment or with concurrent CYP3A4 inhibitors.

Pediatrics (≥6 years, weight ≥25 kg):

• Extended-Release Capsule:
• Initial: 2 mg once daily.
• May be increased to 4 mg once daily after 2 weeks if tolerated and clinically indicated.

Elderly:

• No dose adjustment generally required, but start at the lower end of the dosing range due to increased sensitivity.

Renal Impairment:

• Moderate to Severe Impairment (CrCl 10–30 mL/min):
• Reduce dose: IR 1 mg twice daily or ER 2 mg once daily.

Hepatic Impairment:

• Moderate Impairment (Child-Pugh Class B):
• IR 1 mg twice daily or ER 2 mg once daily.
• Severe Hepatic Impairment (Child-Pugh Class C):
• Not recommended.

Route of Administration:

• Oral (tablet or extended-release capsule); swallow whole, do not crush or chew.

Tolterodine tartrate is a competitive muscarinic receptor antagonist with selectivity for urinary bladder over salivary glands. It acts primarily on M2 and M3 muscarinic receptors located on the detrusor muscle of the bladder wall. By inhibiting cholinergic (acetylcholine-mediated) stimulation of these receptors, tolterodine reduces detrusor muscle contractions, thereby increasing bladder capacity and reducing symptoms of urgency, frequency, and urge incontinence associated with overactive bladder.

• Absorption:
• Rapid oral absorption. Bioavailability: ~77% for extended-release; ~65% for immediate-release due to first-pass metabolism.
• Distribution:
• Widely distributed; plasma protein binding ~96.3% for the parent drug and 98% for the active metabolite.
• Metabolism:
• Hepatic metabolism via CYP2D6 to 5-hydroxymethyl tolterodine (active metabolite), and via CYP3A4 in poor metabolizers.
• Elimination:
• Half-life: 2–4 hours (parent drug), 6–8 hours (active metabolite).
• Excretion: Primarily renal (77%, including metabolites); 17% via feces.
• Onset of Action:
• Therapeutic response typically seen within 4–8 weeks of consistent use.

• Pregnancy:
• FDA Pregnancy Category C.
• Animal studies have shown adverse fetal effects; no well-controlled human studies. Use only if potential benefit justifies potential risk.
• Lactation:
• Unknown whether tolterodine or its metabolites are excreted in human milk. Due to potential for serious adverse reactions in nursing infants, caution is advised; consider discontinuing drug or breastfeeding.
• Recommendation:
• Avoid use during pregnancy unless absolutely necessary. Breastfeeding mothers should use alternate therapy or cease nursing.

• Primary Class:
• Antimuscarinic Agent / Anticholinergic
• Subclass:
• Urinary Antispasmodic (Selective for bladder muscarinic receptors)

• Known hypersensitivity to tolterodine or any component of the formulation
• Urinary retention
• Gastric retention (e.g., pyloric stenosis)
• Uncontrolled narrow-angle glaucoma
• Severe hepatic impairment (Child-Pugh Class C)

• Central Nervous System Effects:
• Risk of headache, dizziness, and somnolence; may impair driving or operating machinery.
• Cognitive Impairment:
• Use with caution in elderly; increased risk of memory loss, confusion, and delirium.
• QT Interval Prolongation:
• Use cautiously in patients with known QT prolongation or those taking other QT-prolonging drugs.
• Bladder Outlet Obstruction or Decreased GI Motility:
• May worsen symptoms; monitor closely.
• Hepatic/Renal Dysfunction:
• Dose adjustments required. Use with caution.
• Pediatric Use:
• Only approved for use in specific cases of NDO in children ≥6 years and weighing ≥25 kg.

Common Side Effects (≥1%):

• Nervous System:
• Headache, dizziness, somnolence
• Gastrointestinal:
• Dry mouth, constipation, dyspepsia, abdominal pain
• Ocular:
• Blurred vision, dry eyes
• Urinary:
• Urinary tract infection, dysuria

Serious/Rare Side Effects:

• Cardiac:
• QT prolongation, tachycardia, palpitations
• CNS:
• Cognitive dysfunction, confusion (especially in elderly)
• Allergic Reactions:
• Angioedema, anaphylaxis (rare)

Timing & Severity:

• Dry mouth and headache typically occur early and may be dose-dependent; CNS and cardiac effects are rare but may require discontinuation.

Major Drug Interactions:

• CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin):
• Increased plasma levels; consider dose reduction.
• CYP2D6 poor metabolizers:
• Increased levels of tolterodine; similar dose reduction applies.
• Other anticholinergics:
• Additive side effects (dry mouth, constipation, confusion).
• QT-prolonging drugs (e.g., amiodarone, sotalol):
• Additive risk of arrhythmias.

Food Interactions:

• No significant food interactions reported.

Alcohol:

• May potentiate CNS depressant effects such as drowsiness.

Enzyme Involvement:

• Metabolized mainly by CYP2D6 and CYP3A4.

• 2023 FDA Advisory (USA):
• Strengthened warning on cognitive impairment risks in elderly patients using anticholinergics including tolterodine.
• 2024 EMA Guideline Review:
• Reaffirmed pediatric indication limited to neurogenic detrusor overactivity with close monitoring.
• Clinical Practice Trends:
• Preference shifting toward newer β3-adrenergic agonists (e.g., mirabegron) in patients at risk for cognitive side effects.

• Temperature:
• Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C.
• Humidity/Light:
• Protect from excessive moisture and light.
• Handling Precautions:
• Store in tightly closed containers. Do not crush or chew extended-release capsules.
• Special Instructions:
• No refrigeration or reconstitution required.