Products
Fesoterodine is commercially available in the form of sustained-release tablets (Toviaz). It has been approved in the EU since 2007 and in many countries since 2008.
Structure and properties
Fesoterodine (C26H37NO3, Mr = 411.58 g/mol) is present in drugs as fesoterodine fumarate. It is an ester prodrug and is rapidly and completely hydrolyzed to its active metabolite desfesoterodine (tovedeso, 5-hydroxymethyltolterodine). This metabolite is also formed by CYP2D6 from tolterodine (Detrusitol), which is approved for the same indication.
Effects
Fesoterodine (ATC G04BD11) is a competitive and specific muscarinic receptor antagonist. Full effects are delayed within 2-8 weeks. The potential advantage of fesoterodine over tolterodine is the lower interindividual variability in ester hydrolysis. Indeed, a not insignificant proportion of the population is unable to form the active metabolite from tolterodine (CYP2D6 poor metabolizers).
Indications
For the treatment of hyperactive bladder.
Dosage
According to the drug label. Fesoterodine is taken once daily with or without food. The maximum daily dose is 8 mg.
Contraindications
- Hypersensitivity
- Urinary retention
- Stomach retention
- Untreated narrow-angle glaucoma
- Myasthenia gravis
- Severe impairment of liver function
- Concurrent use of strong or moderate CYP3A4 inhibitors in patients with moderate to severe hepatic or renal impairment.
- Shweree ulcerative colitis
- Toxic megacolon
For complete precautions, see the drug label.
Interactions
Fesoterodine is rapidly and completely hydrolyzed to the active metabolite 5-hydroxymethyltolterodine, which is a substrate of CYP2D6 and CYP3A4. Therefore, appropriate CYP inhibitors may increase the concentration of the metabolite and enhance its effects and adverse effects. Other anticholinergics, such as tricyclic antidepressants, may increase the adverse effects. Fesoterodine may decrease the effects of prokinetics.
Adverse effects
The most common possible adverse effects include dry mouth, urinary tract infection, dysuria, dizziness, insomnia, headache, dry eyes, dry throat, lower abdominal pain, diarrhea, dyspepsia, constipation, and nausea.