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| Clinical data | |
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| Trade names | Vesicare, Vesicare LS |
| Other names | YM905 |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a605019 |
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| Routes of administration | By mouth |
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| Pharmacokinetic data | |
| Bioavailability | 90% |
| Protein binding | 98% |
| Metabolism | CYP3A4 |
| Metabolites | Glucuronide,N-oxide, others |
| Eliminationhalf-life | 45 to 68 hours |
| Excretion | Kidney (69.2%) and fecal (22.5%) |
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| CAS Number | |
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| DrugBank |
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| Chemical and physical data | |
| Formula | C23H26N2O2 |
| Molar mass | 362.473 g·mol−1 |
| 3D model (JSmol) | |
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Solifenacin, sold as the brand nameVesicare[a] among others, is a medicine used to treatoveractive bladder and neurogenic detrusor overactivity (NDO).[1][2] It may help withincontinence,urinary frequency, andurinary urgency.[3]
Benefits appear similar to other medications in the class.[4] It is taken by mouth.[1]
Common side effects include dry mouth, constipation, andurinary tract infection.[1][2] Severe side effects may includeurinary retention,QT prolongation,hallucinations,glaucoma, andanaphylaxis.[1][3][2] It is unclear if use is safe duringpregnancy.[1] It is of theantimuscarinic class and works by decreasingbladder contractions.[1]
Solifenacin was approved for medical use in the United States in 2004.[1][2][5] In 2023, it was the 245th most commonly prescribed medication in the United States, with more than 1 million prescriptions.[6][7]
It is used to treatoveractive bladder.[1] It may help withincontinence,urinary frequency, andurinary urgency.[3]
Benefits appear similar to other antimuscarinics such asoxybutynin,tolterodine, anddarifenacin.[4]
It is also used to treat neurogenic detrusor overactivity (NDO), a form of bladder dysfunction related to neurological impairment, in children ages two years and older.[2] NDO is a dysfunction of the bladder that results from disease or injury in the nervous system.[2] NDO may be related to congenital conditions (often-inherited conditions beginning at or before birth), such as spina bifida (myelomeningocele), or other conditions such as spinal cord injury.[2] With NDO, there is overactivity of the bladder wall muscle, which normally relaxes to allow storage of urine.[2] The bladder wall muscle overactivity results in sporadic bladder muscle contraction, which increases pressure in the bladder and decreases the volume of urine the bladder can hold.[2] If NDO is not treated, increased pressure in the bladder can put the upper urinary tract at risk of harm, including possible permanent damage to the kidneys.[2] In addition, spontaneous bladder muscle contractions can lead to unexpected and frequent leakage of urine with symptoms of urinary urgency (immediate urge to urinate), frequency (urinating more often than normal) and incontinence (loss of bladder control).[2]
Solifenacin is contraindicated for people withurinary retention, gastric retention, uncontrolled or poorly controlled closed-angleglaucoma, severe liver disease (Child-Pugh class C),[8] andhemodialysis.[9]
Long QT syndrome is not a contraindication although solifenacin, liketolterodine anddarifenacin, binds tohERG channels of the heart and may prolong theQT interval. This mechanism appears to be seldom clinically relevant.[10]
Solifenacin is not to be used in people with gastric retention (reduced emptying of the stomach), uncontrolled narrow angle glaucoma (fluid buildup in the eye which raises eye pressure) or hypersensitivity (allergic reaction) to solifenacin or any of its components.[2] Solifenacin is also not recommended for use in people with severe liver failure, clinically significant bladder outlet obstruction in the absence of clean intermittent catheterization, decreased gastrointestinal motility (slowed intestinal contractions), or at high risk of QT prolongation (an electrical disturbance where the heart muscle takes longer than normal to recharge between beats), including people with a known history of QT prolongation and people taking medications known to prolong the QT interval.[2]
The most commonside effects of solifenacin aredry mouth, constipation and urinary tract infection.[2] As all anticholinergics, solifenacin may rarely causehyperthermia due to decreasedperspiration.[8] Somnolence (sleepiness or drowsiness) has been reported.[2] Severe allergic reactions, such as angioedema (swelling beneath the skin) and anaphylaxis, have been reported in people treated with solifenacin succinate and may be life-threatening.[2]
Solifenacin is metabolized in the liver by thecytochrome P450 enzymeCYP3A4. When administered concomitantly with drugs thatinhibit CYP3A4, such asketoconazole, the metabolism of solifenacin is impaired, leading to an increase in its concentration in the body and a reduction in its excretion.[8]
As stated above, solifenacin may also prolong the QT interval. Therefore, administering it concomitantly with drugs which also have this effect, such asmoxifloxacin orpimozide, can theoretically increase the risk ofarrhythmia.[1]
Solifenacin is acompetitivecholinergic receptorantagonist,selective for theM3 receptor subtype. However, it is said to also act as an antagonist of the other fourmuscarinic acetylcholine receptors.[11]
The binding ofacetylcholine to these receptors, particularly M3, plays a critical role in the contraction ofsmooth muscle. By preventing the binding of acetylcholine to these receptors, solifenacin reduces smooth muscletone in thebladder, 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.[9]
Peak plasma concentrations are reached three to eight hours after absorption from the gut. In the bloodstream, 98% of the substance are bound toplasma proteins, mainly acidic ones. Metabolism is mediated by the liver enzyme CYP3A4 and possibly others. There is one knownactive metabolite, 4R-hydroxysolifenacin, and three inactive ones, theN-glucuronide, theN-oxide and the 4R-hydroxy-N-oxide. Theelimination half-life is 45 to 68 hours. 69% of the substance, both in its original form and as metabolites, are excretedrenally and 23% via the feces.[9]
Like other anticholinergics, solifenacin is anester of acarboxylic acid containing (at least) anaromatic ring with an alcohol containing a nitrogen atom. While in the prototype anticholinergicatropine the bicyclic ring istropane, solifenacin replaces it withquinuclidine.
The free base is a yellow oil, while the salt solifenacinsuccinate forms yellowish crystals.[12]
The compound was studied using animal models by theYamanouchi Pharmaceutical Co., Ltd. of Tokyo, Japan. It was known as YM905 when under study in the early 2000s.[13]
Solifenacin was approved for medical used in the United States in 2004 with an indication to treat overactive bladder in adults 18 years and older.[2][5]
In May 2020, solifenacin was approved for medical use in the United States with an indication to treat neurogenic detrusor overactivity (NDO), a form of bladder dysfunction related to neurological impairment, in children ages two years and older.[2]
The efficacy of solifenacin to treat neurogenic detrusor overactivity (NDO) was established in two clinical trials with a total of 95 pediatric NDO participants, ages two to 17 years old.[2] The studies were designed to measure (as a primary efficacy endpoint) the maximum amount of urine the bladder could hold after 24 weeks of treatment.[2] In the first study, 17 participants ages two to less than five years old were able to hold an average of 39 mL more urine than when the study began.[2] In the second study, 49 participants ages five to 17 years were able to hold an average of 57 mL more urine than when the study began.[2] Reductions in spontaneous bladder contractions, bladder pressure and number of incontinence episodes were also observed in both studies.[2] The approval of Vesicare LS was granted to Astellas Pharma US, Inc.[2]
Theinternational nonproprietary name (INN) is solifenacin.[14] It is manufactured and marketed byAstellas,GlaxoSmithKline[1] andTeva Pharmaceutical Industries.[15]
A 2006cost-effectiveness study found that 5 mg solifenacin had the lowest cost and highest effectiveness amonganticholinergic drugs used to treatoveractive bladder in the United States, with an average medical cost per successfully treated patient of $6863 per year.[16] By 2019, with the introduction of generics, the retail cost of a month's supply was down to $20 in the US.
This article incorporates text from this source, which is in thepublic domain.
