Solifenacin

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Solifenacin
Solifenacin Structural Formulae V.1.svg
Systematic (IUPAC) name
1-azabicyclo[2.2.2]oct-3-yl (1R)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate
Clinical data
Trade names Vesicare
AHFS/Drugs.com monograph
MedlinePlus a605019
Licence data US FDA:link
Pregnancy cat. B3 (AU) C (US)
Legal status POM (UK) -only (US)
Routes Oral
Pharmacokinetic data
Bioavailability 90%
Protein binding 98%
Half-life 45 to 68 hours
Excretion Renal (69.2%) and fecal (22.5%)
Identifiers
CAS number 242478-37-1 N
ATC code G04BD08
PubChem CID 154059
DrugBank DB01591
ChemSpider 135771 N
UNII A8910SQJ1U YesY
ChEMBL CHEMBL1734 N
Chemical data
Formula C23H26N2O2 
Mol. mass 362.465 g/mol
 N (what is this?)  (verify)

Solifenacin (INN, trade name Vesicare) is a medicine of the antimuscarinic class and was developed for treating contraction of overactive bladder with[1] urge incontinence. It is manufactured and marketed by Astellas, Teva Pharmaceutical Industries and GlaxoSmithKline

Pharmacology[edit]

Mechanism of action[edit]

Solifenacin is a competitive cholinergic receptor antagonist. The binding of acetylcholine to these receptors, particularly the M3 receptor subtype, 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.

Contraindications[edit]

Solifenacin should not be taken by people with a history of previous hypersensitivity to it, urinary retention, gastric retention, uncontrolled or poorly controlled closed-angle glaucoma, or severe liver disease (Child-Pugh class C).[2] It is also contraindicated in long QT syndrome, as solifenacin, like tolterodine and darifenacin, binds to HERG channels and may prolong the QT interval.

Medical uses[edit]

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. The manufacturer recommends that the dosage of solifenacin not exceed 5 mg a day if it is taken with a potent CYP3A4 inhibitor.[2]

As stated above, solifenacin may also prolong the QT interval. Therefore, it should not be administered concomitantly with drugs which also have this effect, such as moxifloxacin or pimozide.

Side effects[edit]

Main article: Anticholinergic

The most common side effects of solifenacin are dry mouth, blurred vision, and constipation. As all anticholinergics, solifenacin may rarely cause heat prostration due to decreased perspiration.[2]

Pharmacoeconomics[edit]

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.[3]

References[edit]

  1. ^ Goldman, Lee (2011). Goldman's Cecil Medicine (24th ed.). Philadelphia: Elsevier Saunders. p. 343. ISBN 1437727883. 
  2. ^ a b c Lexi-Comp (December 2009). "Solifenacin". The Merck Manual Professional.  Retrieved on June 10, 2011.
  3. ^ Ko Y, Malone DC, Armstrong EP (Dec 2006). "Pharmacoeconomic evaluation of antimuscarinic agents for the treatment of overactive bladder". Pharmacotherapy 26 (12): 1694–702. doi:10.1592/phco.26.12.1694. PMID 17125433.