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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 |
Elimination half-life | 45 to 68 hours |
Excretion | Kidney (69.2%) and fecal (22.5%) |
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Chemical and physical data | |
Formula | C23H26N2O2 |
Molar mass | 362.473 g·mol−1 |
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Solifenacin, sold as the brand name Vesicare [lower-alpha 1] among others, is a medicine used to treat overactive bladder and neurogenic detrusor overactivity (NDO). [1] [2] It may help with incontinence, urinary frequency, and urinary 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, and urinary tract infection. [1] [2] Severe side effects may include urinary retention, QT prolongation, hallucinations, glaucoma, and anaphylaxis. [1] [3] [2] It is unclear if use is safe during pregnancy. [1] It is of the antimuscarinic class and works by decreasing bladder contractions. [1]
Solifenacin was approved for medical use in the United States in 2004. [1] [2] [5] In 2020, it was the 266th most commonly prescribed medication in the United States, with more than 1 million prescriptions. [6] [7]
It is used to treat overactive bladder. [1] It may help with incontinence, urinary frequency, and urinary urgency. [3]
Benefits appear similar to other antimuscarinics such as oxybutynin, tolterodine, and darifenacin. [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 with urinary retention, gastric retention, uncontrolled or poorly controlled closed-angle glaucoma, severe liver disease (Child-Pugh class C), [8] and hemodialysis. [9]
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. [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 common side effects of solifenacin are dry mouth, constipation and urinary tract infection. [2] As all anticholinergics, solifenacin may rarely cause hyperthermia due to decreased perspiration. [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 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. [8]
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. [1]
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. [9]
Peak plasma concentrations are reached three to eight 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. [9]
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.
The free base is a yellow oil, while the salt solifenacin succinate forms yellowish crystals. [11]
The compound was studied using animal models by the Yamanouchi Pharmaceutical Co., Ltd. of Tokyo, Japan. It was known as YM905 when under study in the early 2000s. [12]
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]
The INN is solifenacin. [13] It is manufactured and marketed by Astellas, GlaxoSmithKline [1] and Teva Pharmaceutical Industries. [14]
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. [15] By 2019, with the introduction of generics, the retail cost of a month's supply was down to $20 in the US.
The bladder is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans, the bladder is a distensible organ that sits on the pelvic floor. Urine enters the bladder via the ureters and exits via the urethra. The typical adult human bladder will hold between 300 and 500 ml before the urge to empty occurs, but can hold considerably more.
Urinary incontinence (UI), also known as involuntary urination, is any uncontrolled leakage of urine. It is a common and distressing problem, which may have a large impact on quality of life. It has been identified as an important issue in geriatric health care. The term enuresis is often used to refer to urinary incontinence primarily in children, such as nocturnal enuresis. UI is an example of a stigmatized medical condition, which creates barriers to successful management and makes the problem worse. People may be too embarrassed to seek medical help, and attempt to self-manage the symptom in secrecy from others.
Autonomic neuropathy is a form of polyneuropathy that affects the non-voluntary, non-sensory nervous system, affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a person's conscious control and function automatically. Autonomic nerve fibers form large collections in the thorax, abdomen, and pelvis outside the spinal cord. They have connections with the spinal cord and ultimately the brain, however. Most commonly autonomic neuropathy is seen in persons with long-standing diabetes mellitus type 1 and 2. In most—but not all—cases, autonomic neuropathy occurs alongside other forms of neuropathy, such as sensory neuropathy.
Enuresis is a repeated inability to control urination. Use of the term is usually limited to describing people old enough to be expected to exercise such control. Involuntary urination is also known as urinary incontinence. The term "enuresis" comes from the Ancient Greek: ἐνούρησις, romanized: enoúrēsis.
Urinary retention is an inability to completely empty the bladder. Onset can be sudden or gradual. When of sudden onset, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include loss of bladder control, mild lower abdominal pain, and a weak urine stream. Those with long-term problems are at risk of urinary tract infections.
Tolterodine, sold under the brand name Detrol among others, is a medication used to treat frequent urination, urinary incontinence, or urinary urgency. Effects are seen within an hour. It is taken by mouth.
Oxybutynin, sold as under the brand names Ditropan among others, is a medication used to treat overactive bladder. It works similar to tolterodine, Darifenacin, and Solifenacin. While used for bed wetting in children, evidence to support this use is poor. It is taken by mouth or applied to the skin.
Darifenacin is a medication used to treat urinary incontinence due to an overactive bladder. It was discovered by scientists at the Pfizer research site in Sandwich, UK under the identifier UK-88,525 and used to be marketed by Novartis. In 2010, the US rights were sold to Warner Chilcott for US$400 million.
Bladder sphincter dyssynergia is a consequence of a neurological pathology such as spinal injury or multiple sclerosis which disrupts central nervous system regulation of the micturition (urination) reflex resulting in dyscoordination of the detrusor muscles of the bladder and the male or female external urethral sphincter muscles. In normal lower urinary tract function, these two separate muscle structures act in synergistic coordination. But in this neurogenic disorder, the urethral sphincter muscle, instead of relaxing completely during voiding, dyssynergically contracts causing the flow to be interrupted and the bladder pressure to rise.
Neurogenic bladder dysfunction, or neurogenic bladder, refers to urinary bladder problems due to disease or injury of the central nervous system or peripheral nerves involved in the control of urination. There are multiple types of neurogenic bladder depending on the underlying cause and the symptoms. Symptoms include overactive bladder, urinary urgency, frequency, incontinence or difficulty passing urine. A range of diseases or conditions can cause neurogenic bladder including spinal cord injury, multiple sclerosis, stroke, brain injury, spina bifida, peripheral nerve damage, Parkinson's disease, or other neurodegenerative diseases. Neurogenic bladder can be diagnosed through a history and physical as well as imaging and more specialized testing. Treatment depends on underlying disease as well as symptoms and can be managed with behavioral changes, medications, surgeries, or other procedures. The symptoms of neurogenic bladder, especially incontinence, can have a significant impact on quality of life.
The detrusor muscle, also detrusor urinae muscle, muscularis propria of the urinary bladder and muscularis propria, is smooth muscle found in the wall of the bladder. The detrusor muscle remains relaxed to allow the bladder to store urine, and contracts during urination to release urine. Related are the urethral sphincter muscles which envelop the urethra to control the flow of urine when they contract.
Overactive bladder (OAB) is a common condition where there is a frequent feeling of needing to urinate to a degree that it negatively affects a person's life. The frequent need to urinate may occur during the day, at night, or both. Loss of bladder control may occur with this condition. Overactive bladder affects approximately 11% of the population and more than 40% of people with overactive bladder have incontinence. Conversely, about 40% to 70% of urinary incontinence is due to overactive bladder. Overactive bladder is not life-threatening, but most people with the condition have problems for years.
Propiverine is an anticholinergic drug used for the treatment of urinary urgency, frequency and urge incontinence, all symptoms of overactive bladder syndrome. It is a muscarinic antagonist. A modified release preparation is also available, taken once daily.
Urogynecology or urogynaecology is a surgical sub-specialty of urology and gynecology.
Urodynamic testing or urodynamics is a study that assesses how the bladder and urethra are performing their job of storing and releasing urine. Urodynamic tests can help explain symptoms such as:
Overflow incontinence is a concept of urinary incontinence, characterized by the involuntary release of urine from an overfull urinary bladder, often in the absence of any urge to urinate. This condition occurs in people who have a blockage of the bladder outlet, or when the muscle that expels urine from the bladder is too weak to empty the bladder normally. Overflow incontinence may also be a side effect of certain medications.
Mirabegron, sold under the brand name Myrbetriq among others, is a medication used to treat overactive bladder. Its benefits are similar to antimuscarinic medication such as solifenacin or tolterodine. It is taken by mouth.
Autonomic drugs can either inhibit or enhance the functions of the parasympathetic and sympathetic nervous systems. This type of drug can be used to treat a wide range of diseases, such as glaucoma, asthma, urinary, gastrointestinal and cardiopulmonary disorders.
Vibegron, sold under the brand name Gemtesa, is a medication for the treatment of overactive bladder. Vibegron is a selective beta-3 adrenergic receptor agonist.
Prof Clare Fowler CBE is a British physician and academic who created the subspecialty of uro-neurology, a medical field that combines urology and neurology. This work was done at the Institute of Neurology, University College London, where she is an emeritus professor.