|Metabolites||Glucuronide, N-oxide, others|
|Elimination half-life||45 to 68 hours|
|Excretion||Kidney (69.2%) and fecal (22.5%)|
|Chemical and physical data|
|Molar mass||362.465 g/mol g·mol−1|
|3D model (JSmol)|
|(what is this?)|
Solifenacin, sold as the brand name Vesicare among others, is a medicine used to treat overactive bladder. It may help with incontinence, urinary frequency, and urinary urgency. Benefits appear similar to other medications in the class. It is taken by mouth.
Common side effects include dry mouth and constipation. Severe side effects may include urinary retention, QT prolongation, hallucinations, and glaucoma. It is unclear if use is safe during pregnancy. It is of the antimuscarinic class and works by decreasing bladder contractions.
Solifenacin was approved for medical use in the United States in 2004. A month supply in the United Kingdom costs the NHS about 27.62 £ as of 2019. In the United States the wholesale cost of this amount is about 370 USD. In 2016 it was the 170th most prescribed medication in the United States with more than 3 million prescriptions.
Solifenacin is contraindicated for people with urinary retention, gastric retention, uncontrolled or poorly controlled closed-angle glaucoma, severe liver disease (Child-Pugh class C), and hemodialysis.
Long QT syndrome is not a contraindication although solifenacin, like tolterodine and darifenacin, binds to hERG channels of the heart and may prolong the QT interval. This mechanism appears to be seldom clinically relevant.
Solifenacin is metabolized in the liver by the cytochrome P450 enzyme CYP3A4. When administered concomitantly with drugs that inhibit CYP3A4, such as ketoconazole, the metabolism of solifenacin is impaired, leading to an increase in its concentration in the body and a reduction in its excretion.
As stated above, solifenacin may also prolong the QT interval. Therefore, administering it concomitantly with drugs which also have this effect, such as moxifloxacin or pimozide, can theoretically increase the risk of arrhythmia.
Mechanism of action
Solifenacin is a competitive cholinergic receptor antagonist, selective for the M3 receptor subtype. The binding of acetylcholine to these receptors, particularly M3, plays a critical role in the contraction of smooth muscle. By preventing the binding of acetylcholine to these receptors, solifenacin reduces smooth muscle tone in the bladder, allowing the bladder to retain larger volumes of urine and reducing the number of micturition, urgency and incontinence episodes. Because of a long elimination half life, a once-a-day dose can offer 24-hour control of the urinary bladder smooth muscle tone.
Peak plasma concentrations are reached 3 to 8 hours after absorption from the gut. In the bloodstream, 98% of the substance are bound to plasma proteins, mainly acidic ones. Metabolism is mediated by the liver enzyme CYP3A4 and possibly others. There is one known active metabolite, 4R-hydroxysolifenacin, and three inactive ones, the N-glucuronide, the N-oxide and the 4R-hydroxy-N-oxide. The elimination half-life is 45 to 68 hours. 69% of the substance, both in its original form and as metabolites, are excreted renally and 23% via the feces.
Like other anticholinergics, solifenacin is an ester of a carboxylic acid containing (at least) an aromatic ring with an alcohol containing a nitrogen atom. While in the prototype anticholinergic atropine the bicyclic ring is tropane, solifenacin replaces it with quinuclidine.
Society and culture
A 2006 cost-effectiveness study found that 5 mg solifenacin had the lowest cost and highest effectiveness among anticholinergic drugs used to treat overactive bladder in the United States, with an average medical cost per successfully treated patient of $6863 per year.
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