Solifenacin, sold as the brand name Vesicare among others, is a medicine used to treat

overactive bladder 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 bl ...

and neurogenic detrusor overactivity (NDO). It may help with

incontinence Incontinence or Incontinent may refer to: * Urinary incontinence, the most commonly occurring type of incontinence, the involuntary excretion of urine *Fecal incontinence Fecal incontinence (FI), or in some forms, encopresis, is a lack of con ...

urinary frequency Frequent urination, or urinary frequency (sometimes called pollakiuria), is the need to urinate more often than usual. Diuretics are medications that increase urinary frequency. Nocturia is the need of frequent urination at night. The most common ...

, and

urinary urgency Urination is the release of urine from the bladder through the urethra in placental mammals, or through the cloaca in other vertebrates. It is the urinary system's form of excretion. It is also known medically as micturition, voiding, uresi ...

. Benefits appear similar to other medications in the class. It is taken by mouth. Common side effects include dry mouth, constipation, and

urinary tract infection A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. Lower urinary tract infections may involve the bladder (cystitis) or urethra (urethritis) while upper urinary tract infections affect the kidney (pyel ...

. Severe side effects may include

urinary retention 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 urinary incont ...

QT prolongation QT or Qt may refer to: Businesses * The Qt Company, a Finnish software developer * QT Hotels & Resorts, an Australasian hospitality provider * QT Inc., an American bracelet manufacturer * QuikTrip, an American convenience store chain People * ...

hallucination A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...

glaucoma Glaucoma is a group of eye diseases that can lead to damage of the optic nerve. The optic nerve transmits visual information from the eye to the brain. Glaucoma may cause vision loss if left untreated. It has been called the "silent thief of ...

, and

anaphylaxis Anaphylaxis (Greek: 'up' + 'guarding') is a serious, potentially fatal allergic reaction and medical emergency that is rapid in onset and requires immediate medical attention regardless of the use of emergency medication on site. It typicall ...

. It is unclear if use is safe during

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

. It is of the

antimuscarinic A muscarinic acetylcholine receptor antagonist, also simply known as a muscarinic antagonist or as an antimuscarinic agent, is a type of anticholinergic drug that blocks the activity of the muscarinic acetylcholine receptors (mAChRs). The muscarin ...

class and works by decreasing

bladder The bladder () is a hollow organ in humans and other vertebrates that stores urine from the kidneys. In placental mammals, urine enters the bladder via the ureters and exits via the urethra during urination. In humans, the bladder is a distens ...

contractions. Solifenacin was approved for medical use in the United States in 2004. In 2022, it was the 210th most commonly prescribed medication in the United States, with more than 1million prescriptions.

Medical use

It is used to treat

. It may help with

, and

. Benefits appear similar to other antimuscarinics such as

oxybutynin Oxybutynin, sold under the brand name Ditropan among others, is an anticholinergic medication primarily used to treat overactive bladder. It is widely considered a first-line therapy for overactive bladder due to its well-studied side effect ...

tolterodine 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. Common side effects include head ...

, and darifenacin. 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. NDO is a dysfunction of the bladder that results from disease or injury in the nervous system. 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. With NDO, there is overactivity of the bladder wall muscle, which normally relaxes to allow storage of urine. 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. 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. 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).

Contraindications

Solifenacin is contraindicated for people with

, gastric retention, uncontrolled or poorly controlled closed-angle

, severe liver disease ( Child-Pugh class C), and

hemodialysis Hemodialysis, American and British English spelling differences#ae and oe, also spelled haemodialysis, or simply ''"'dialysis'"'', is a process of filtering the blood of a person whose kidneys are not working normally. This type of Kidney dialys ...

Long QT syndrome Long QT syndrome (LQTS) is a condition affecting repolarization (relaxing) of the heart after a heartbeat, giving rise to an abnormally lengthy QT interval. It results in an increased risk of an irregular heartbeat which can result in fainti ...

is not a contraindication although solifenacin, like

and darifenacin, binds to hERG channels of the heart and may prolong the

QT interval The QT interval is a measurement made on an Electrocardiography, electrocardiogram used to assess some of the electrical properties of the heart. It is calculated as the time from the start of the QRS complex, Q wave to the end of the T wave, an ...

. This mechanism appears to be seldom clinically relevant. 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. 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.

Side effects

The most common

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s of solifenacin are

dry mouth Xerostomia, also known as dry mouth, is a subjective complaint of dryness in the mouth, which may be associated with a change in the composition of saliva, reduced salivary flow, or have no identifiable cause. This symptom is very common and is o ...

, constipation and urinary tract infection. As all anticholinergics, solifenacin may rarely cause

hyperthermia Hyperthermia, also known as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme te ...

due to decreased

perspiration Perspiration, also known as sweat, is the fluid secreted by sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and Apocrine sweat gland, apocrine glands. The eccrine sweat glands are distribu ...

. Somnolence (sleepiness or drowsiness) has been reported. 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.

Interactions

Solifenacin is metabolized in the liver by the

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

enzyme

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

. When administered concomitantly with drugs that inhibit CYP3A4, such as

ketoconazole Ketoconazole, sold under the brand name Nizoral, among others, is an antiandrogen, antifungal drug, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin inf ...

, 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 Moxifloxacin is an antibiotic, used to treat bacterial infections, including pneumonia, conjunctivitis, endocarditis, tuberculosis, and sinusitis. It can be given by mouth, by injection into a vein, and as an eye drop. Common side effec ...

pimozide Pimozide (sold under the brand name Orap) is a neuroleptic medication, drug of the diphenylbutylpiperidine class. It was discovered at Janssen Pharmaceutica in 1963. It has a high potency compared to chlorpromazine (ratio 50-70:1). On a weigh ...

, can theoretically increase the risk of

arrhythmia Arrhythmias, also known as cardiac arrhythmias, are irregularities in the cardiac cycle, heartbeat, including when it is too fast or too slow. Essentially, this is anything but normal sinus rhythm. A resting heart rate that is too fast – ab ...

Pharmacology

Mechanism of action

Solifenacin is a

competitive Competition is a rivalry where two or more parties strive for a common goal which cannot be shared: where one's gain is the other's loss (an example of which is a zero-sum game). Competition can arise between entities such as organisms, indi ...

cholinergic receptor

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.selective for the M₃ receptor subtype. However, it is said to also act as an antagonist of the other four

muscarinic acetylcholine receptor Muscarinic acetylcholine receptors (mAChRs) are acetylcholine receptors that form G protein-coupled receptor, G protein-coupled receptor complexes in the cell membranes of certain neurons and other Cell (biology), cells. They play several role ...

s. The binding of

acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

to these receptors, particularly M₃, plays a critical role in the contraction of

smooth muscle Smooth muscle is one of the three major types of vertebrate muscle tissue, the others being skeletal and cardiac muscle. It can also be found in invertebrates and is controlled by the autonomic nervous system. It is non- striated, so-called bec ...

. By preventing the binding of acetylcholine to these receptors, solifenacin reduces smooth muscle

tone Tone may refer to: Visual arts and color-related * Tone (color theory), a mix of tint and shade, in painting and color theory * Tone (color), the lightness or brightness (as well as darkness) of a color * Toning (coin), color change in coins * ...

in the

, 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.

Pharmacokinetics

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 protein Plasma proteins, sometimes referred to as blood proteins, are proteins present in blood plasma. They perform many different functions, including transport of hormones, vitamins and minerals in activity and functioning of the immune system. Other b ...

s, mainly acidic ones. Metabolism is mediated by the liver enzyme CYP3A4 and possibly others. There is one known

active metabolite An active metabolite, or pharmacologically active metabolite is a biologically active metabolite of a xenobiotic substance, such as a drug or environmental chemical. Active metabolites may produce therapeutic effects, as well as harmful effects. ...

, 4''R''-hydroxysolifenacin, and three inactive ones, the ''N''-

glucuronide A glucuronide, also known as glucuronoside, is any substance produced by linking glucuronic acid to another substance via a glycosidic bond. The glucuronides belong to the glycosides. Glucuronidation, the conversion of chemical compounds to glucu ...

, the ''N''-oxide and the 4''R''-hydroxy-''N''-oxide. The

elimination half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...

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.

Chemistry

Like other anticholinergics, solifenacin is an

ester In chemistry, an ester is a compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds contain a distin ...

of a

carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an Substituent, R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl ...

containing (at least) an

aromatic In organic chemistry, aromaticity is a chemical property describing the way in which a conjugated system, conjugated ring of unsaturated bonds, lone pairs, or empty orbitals exhibits a stabilization stronger than would be expected from conjugati ...

ring with an alcohol containing a nitrogen atom. While in the prototype anticholinergic

atropine Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically give ...

the bicyclic ring is

tropane Tropane is a nitrogenous bicyclic organic compound. It is mainly known for the other alkaloids derived from it, which include atropine and cocaine, among others. Tropane alkaloids occur in plants of the families Erythroxylaceae (including coca) ...

, solifenacin replaces it with quinuclidine. The free base is a yellow oil, while the salt solifenacin

succinate Succinic acid () is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological roles as a metabolic intermediate being converted into Fuma ...

forms yellowish crystals.

History

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. 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. 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. 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. 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. 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. 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. Reductions in spontaneous bladder contractions, bladder pressure and number of incontinence episodes were also observed in both studies. The approval of Vesicare LS was granted to Astellas Pharma US, Inc.

Society and culture

The international nonproprietary name (INN) is solifenacin. It is manufactured and marketed by Astellas,

GlaxoSmithKline GSK plc (an acronym from its former name GlaxoSmithKline plc) is a British Multinational corporation, multinational Pharmaceutics, pharmaceutical and biotechnology company with headquarters in London. It was established in 2000 by a Mergers an ...

and

Teva Pharmaceutical Industries Teva Pharmaceutical Industries Ltd. (also known as Teva Pharmaceuticals) is an Israeli multinational pharmaceutical company. Teva specializes primarily in generic drugs, but other business interests include branded-drugs, active pharmaceutical ...

Cost

A 2006

cost-effectiveness Cost-effectiveness analysis (CEA) is a form of economic analysis that compares the relative costs and outcomes (effects) of different courses of action. Cost-effectiveness analysis is distinct from cost–benefit analysis, which assigns a moneta ...

study found that 5 mg solifenacin had the lowest cost and highest effectiveness among

anticholinergic Anticholinergics (anticholinergic agents) are substances that block the action of the acetylcholine (ACh) neurotransmitter at synapses in the central nervous system, central and peripheral nervous system. These agents inhibit the parasympatheti ...

drugs used to treat

in the United States, with an average medical cost per successfully treated patient of $6863 per year. By 2019, with the introduction of generics, the retail cost of a month's supply was down to $20 in the US.

Footnotes

References

{{Portal bar , Medicine 3-Quinuclidinyl esters Astellas Pharma Carbamates Drugs developed by GSK plc HERG blocker M1 receptor antagonists M2 receptor antagonists M3 receptor antagonists M4 receptor antagonists M5 receptor antagonists Tetrahydroisoquinolines Wikipedia medicine articles ready to translate