Tolterodine | Pharmacology Mentor

Generic Name

Tolterodine

Detrol®, Detrol LA® (long‑acting), and generic formulations.

M₁‑M₄ receptor blockade:
Blocks muscarinic receptors in the detrusor muscle, reducing involuntary contractions.
Decreases afferent signaling from stretch receptors to the central nervous system.
Result:
Prolonged bladder capacity and decreased detrusor overactivity.
Acute versus prolonged effects:
Short‑acting formulations produce rapid relief of urgency, while extended‑release (ER) allows once‑daily dosing.

Parameter	Typical value (oral, 4 mg)
Absorption	Rapid, Tmax ~1–1.5 h
Bioavailability	40–50 % (first‑pass hepatic metabolism)
Metabolism	CYP2D6 / CYP3A4 mediated hydroxylation → 78‑hydroxytolterodine
Elimination	Renal excretion (~40 %) and biliary (60 %)
Half‑life	7–9 h (absorption phase); ER forms ~12–14 h
Protein binding	~32 %
Steady‑state	~3–5 days of continuous dosing
Drug interactions	Reduced clearance with strong CYP2D6 inhibitors (e.g., quinidine). ↑CYP3A4 inducers (e.g., rifampin) reduce exposure.

Overactive bladder (OAB) with urgency, frequency, and/or urge‑incontinence.
Urinary bladder outlet obstruction (experimental/off‑label, not standard therapy).
Adjunct for interstitial cystitis in selected patients (off‑label).

Contraindicated in
Severe urinary retention or bladder obstruction.
Megaly of bladder.
Progressive hepatic disease (due to hepatic metabolism).
Absolute warnings
Narrow‑angle glaucoma (ciliary muscarinic blockade increases intraocular pressure).
Severe constipation or paralytic ileus.
Relative cautions
Elderly: increased risk of cognitive impairment, delirium.
Hippocampal dysfunction; avoid in patients with reversible cognitive deficits.
Drug interactions
Antihyperglycemics: possible hypoglycemia.
Anti‑arrhythmics: potential arrhythmia, especially QT prolongation with class III agents.
CYP3A4/2D6 inhibitors & inducers need dose adjustment.

Adults
*Immediate–release (IR)*: 4 mg PO twice daily (BID) or 2 mg PO BID on non‑stimulant days.
*Extended‑release (ER)*: 4 mg PO once daily (QD), preferably in the morning.
Elderly or hepatic impairment:
Start at 2 mg QD (ER) or 2 mg BID (IR), adjust based on tolerability.
Titration
Initiate at lower dose → titrate every 4–7 days to 8 mg QD (ER) if needed.
Missed dose → take next dose at next meal; do not double dose.
Discontinuation → abrupt withdrawal may induce acute urinary retention; taper slowly.

Category	Examples
Common (≥ 5 %)	Dry mouth, constipation, blurred vision, headache, dizziness, urinary retention, nausea
Serious (≤ 1 %)	Acute urinary retention, severe constipation, neurological or psychiatric (confusion, delirium), angioedema (rare)
Emergent	Rapid heart rate, palpitations, syncope

Anticholinergic burden: significant in elderly; monitor cognitive status.

Baseline: renal and hepatic panels, fasting glucose, post‑void residual volume (PVR), ocular exam (if glaucoma risk).
Post‑initiation:
PVR (within 2 weeks).
Cognitive assessment (MMSE or MoCA) in elderly.
Ocular pressure in susceptible patients.
Periodic follow‑up: 2–4 weeks after dose change, then every 6–12 months.

Remember the “dry mouth” check: oral‑dosing antimuscarinics universally cause xerostomia. Encourage chewing gum or sips of water to mitigate discomfort.
Avoid in patients with *underactive bladder*: the risk of retention far outweighs benefit—consider cholinergic agonists instead.
ER vs. IR: Use ER to improve adherence in most patients; only switch to IR if breakthrough urgency occurs.
“Rapid onset” for urgent incontinence: a single 2 mg IR dose can temporarily quell urgency in acute settings.
Drug‑drug interaction pearls:
Co‑administration with quinidine or paroxetine may reduce tolterodine clearance → increase anticholinergic load.
Strong CYP3A4 inducers (rifampin, carbamazepine) reduce serum levels → consider dose escalation.
Post‑ceramic orthopedics: patients on tolterodine have higher risk of slippage during drop‑off rescue because of dry eyes and blurred vision—advise caution with eyewear.
Elderly cognitive screens: even asymptomatic patients on chronic antimuscarinics benefit from annual cognitive assessment; early detection of delirogenic episodes is critical.

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• *Sources: FDA drug label, UpToDate, Goodman & Gilman’s The Pharmacological Basis of Therapeutics.*