Solifenacin

Products

Solifenacin is commercially available in the form of film-coated tablets (Vesicare, generics). It has been approved in many countries since 2006.

Structure and properties

Solifenacin (C23H26N2O2, Mr = 362.5 g/mol) is a tertiary amine and a phenylquinoline derivative that has structural similarities to atropine. It is present in drugs as (1)-(3)-solifenacin succinate, a white to yellowish-white crystalline powder that is highly soluble in water.

Effects

Solifenacin (ATC G04BD08) has parasympatholytic properties. It is a competitive and selective inhibitor of the muscarinic receptor M3, which, along with M2 on the bladder wall muscles, plays an important role in urinary excretion and the pathogenesis of irritable bladder. It should be added as a caveat that despite bladder selectivity, adverse effects on other organs also occur with solifenacin.

Indications

For the treatment of hyperactive bladder associated with the following symptoms: urinary urgency, increased frequency of micturition, and/or urge incontinence.

Dosage

According to the drug label. Solifenacin may be taken once daily because of its long half-life of 45 to 68 hours. It is taken independently of meals.

Contraindications

  • Hypersensitivity
  • Urinary retention
  • Non-adjusted narrow-angle glaucoma
  • Severe gastrointestinal disease
  • Myasthenia gravis
  • Severe liver dysfunction
  • Hemodialysis patients
  • Severe renal insufficiency or moderate hepatic impairment concomitant with a strong CYP3A4 inhibitor, including patients at risk for these conditions.

For complete precautions, see the drug label.

Interactions

Solifenacin is biotransformed by CYP3A4 to predominantly inactive metabolites. Corresponding drug-drug interactions with inhibitors, inducers, and substrates are possible. For example, a relevant increase in AUC was observed with concomitant treatment with the potent CYP inhibitor ketoconazole. Pharmacodynamic interactions are possible with other parasympatholytics, parasympathomimetics, and prokinetics.

Adverse effects

Adverse effects can be attributed largely to the anticholinergic properties of the drug. The most common adverse effects include dry mouth, constipation, nausea, dyspepsia, abdominal pain, and visual disturbances.