Products
Tolterodine is commercially available in the form of sustained-release capsules (Detrusitol SR). It has been approved in many countries since 2000. Its successor product, fesoterodine (Toviaz), was launched in 2008 and desfesoterodine (Tovedeso) in 2019. A non-retarded preparation is also commercially available in the United States (Detrol).
Structure and properties
Tolterodine (C22H31NO, Mr = 325.5 g/mol) is a tertiary amine. It is present in drugs as tolterodine tartrate, a white crystalline powder soluble in water at 12 mg/mL. Tolterodine is biotransformed by CYP2D6 to the active metabolite desfesoterodine (tovedeso). Fesoterodine is also metabolized to the same metabolite, but by ester hydrolysis, which is subject to less interindividual variability.
Effects
Tolterodine (ATC G04BD07) has parasympatholytic properties. It is a competitive inhibitor of the muscarinic receptor on bladder wall muscle, which plays an important role in urinary excretion and the pathogenesis of irritable bladder. According to the literature, tolterodine is not selective for any particular receptor subtype in vitro. However, in vivo, it preferentially binds to the bladder rather than the salivary glands. Nevertheless, dry mouth is the most common adverse effect.
Indications
For the treatment of hyperactive bladder.
Dosage
According to the drug label. The usual dose is 2 to 4 mg with or without food. Because of the sustained-release dosage form, once-daily administration is sufficient despite the comparatively short half-life.
Contraindications
- Hypersensitivity
- Urinary retention
- Severe ulcerative colitis
- Toxic megacolon
- Untreated narrow-angle glaucoma
- Myasthenia gravis
For complete precautions, see the drug label.
Interactions
Tolterodine is metabolized by CYP2D6 and CYP3A4. Corresponding drug-drug interactions are possible. Other interactions have been described with cholinesterase inhibitors, anticholinergics, metoclopramide, and cisapride.
Adverse effects
Adverse effects can be largely attributed to the anticholinergic properties of the drug. The most common adverse effects include dry mouth, drowsiness, fatigue, insomnia, headache, dizziness, visual disturbances, sinusitis, flatulence, dyspepsia, abdominal pain, constipation, dry skin, skin flushing, peripheral edema, and dysuria.
