tolterodine tartrate
Detrol, Detrol LA

Available forms
Available by prescription only
Capsules (extended-release): 2 mg, 4 mg
Tablets: 1 mg, 2 mg

Indications and dosages
 Treatment of patients with overactive bladder with symptoms of urinary frequency, urgency, or urge incontinence. Adults: Initial dose is 2 mg P.O. b.i.d. May lower to 1 mg b.i.d. based on response and tolerance. Or, using extended-release form, give 4 mg P.O. daily. Dose may be reduced to 2 mg P.O. daily of the extended-release formulation based on tolerance and response.
≡ Dosage adjustment. For patients who have significantly reduced hepatic function or who are currently taking a drug that inhibits the cytochrome P-450 3A4 isoenzyme system, recommended dosage is 1 mg b.i.d. of regular form or 2 mg daily of extended-release form.

Pharmacodynamics
Anticholinergic action: Tolterodine is a competitive muscarinic receptor antagonist. Both urinary bladder contraction and salivation are mediated by way of cholinergic muscarinic receptors.

Pharmacokinetics
Absorption: Well absorbed with about 77% bioavailability. Food increases bioavailability by 53%.
Distribution: Volume of distribution is about 113 L. Tolterodine is 96% protein-bound.
Metabolism: Metabolized by the liver primarily by oxidation by the cytochrome P-450 2D6 pathway; leads to formation of a pharmacologically active 5-hydroxymethyl metabolite.
Excretion: Excreted mostly via urine; the rest in feces. Less than 1% of a dose is recovered as unchanged drug, and 5% to 14% is recovered as the active metabolite. Half-life is 2 to 3 1/2 hours.

Contraindications and precautions
Contraindicated in patients with urine or gastric retention and uncontrolled angle-closure glaucoma. Also contraindicated in patients hypersensitive to tolterodine or its components.
  Use cautiously in patients with significantly reduced hepatic or renal function.

Interactions
Drug-drug. Antifungals, such as itraconazole, ketoconazole, and miconazole; cytochrome P-450 3A4 inhibitors, such as macrolide antibiotics (including clarithromycin and erythromycin): Increases tolterodine levels. Doses should be reduced.
Drug-food. Any food: Increases tolterodine absorption. May be used for this effect.

Adverse reactions
CNS: paresthesia, vertigo, dizziness, headache, nervousness, somnolence, fatigue.
CV: hypertension, chest pain.
EENT: abnormal vision (including accommodation), xerophthalmia, pharyngitis, rhinitis, sinusitis.
GI: dry mouth, abdominal pain, constipation, diarrhea, dyspepsia, flatulence, nausea, vomiting.
GU: dysuria, micturition frequency, urine retention, urinary tract infection.
Metabolic: weight gain.
Musculoskeletal: arthralgia, back pain.
Respiratory: bronchitis, cough, upper respiratory tract infection
Skin: pruritus, rash, erythema, dry skin.
Other: flulike symptoms.

Effects on lab test results
None reported.

Overdose and treatment
Overdose can potentially result in severe central anticholinergic effects and should be treated accordingly.
 Perform ECG monitoring if an overdose occurs, with close attention to QT interval.

Special considerations
• Food increases absorption of tolterodine, but no dosage adjustment is needed.
• Dry mouth is the most frequently reported adverse effect.
• Monitor patient for urinary symptoms and adverse reactions.
Pregnant patients
• Use drug during pregnancy only when clearly needed.
Breast-feeding patients
• It isn’t known whether drug appears in breast milk. Drug isn’t recommended for use in breast-feeding women.
Pediatric patients
• Safety and efficacy in children haven’t been established.
Geriatric patients
• No overall differences in safety have been observed between older and younger patients.

Patient education
• Inform patient that antimuscarinics such as tolterodine may produce blurred vision.
• Caution patient to avoid hazardous activities until effects of drug are known.
• Tell patient to swallow extended-release formulation whole.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use