Solifenacin

Solifenacin
Systematic (IUPAC) name
1-azabicyclo[2.2.2]oct-8-yl (1S)-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 242478-38-2 N
ATC code G04BD08
PubChem CID 443938
DrugBank APRD00168
ChemSpider 391992 Y
UNII A8910SQJ1U Y
ChEMBL CHEMBL1734 N
Chemical data
Formula C23H26N2O2 
Mol. mass 362.465 g/mol
SMILES eMolecules & PubChem
 N(what is this?)  (verify)

Solifenacin (INN, trade name Vesicare) is a urinary antispasmodic of the antimuscarinic class. It is used in the treatment of overactive bladder with or without urge incontinence. It is manufactured by Astellas and co-marketed by Astellas and GlaxoSmithKline.

Contents

Pharmacology

Mechanism of action

Solifenacin is a competitive muscarinic acetylcholine 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

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).[1] It is also contraindicated in long QT syndrome, as solifenacin, like tolterodine and darifenacin, binds to HERG channels and may prolong the QT interval.

Interactions

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.[1]

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

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.[1]

Pharmacoeconomics

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.[2]

References

  1. ^ a b c Lexi-Comp (December 2009). "Solifenacin". The Merck Manual Professional. http://www.merck.com/mmpe/lexicomp/solifenacin.html.  Retrieved on June 10, 2011.
  2. ^ 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. 
Urologicals, including antispasmodics (G04B)
Acidifiers
Urinary antispasmodics
(primarily antimuscarinics)
Other urologicals

M: URI

anat/phys/devp/cell

noco/acba/cong/tumr, sysi/epon, urte

proc/itvp, drug (G4B), blte, urte