Solifenacin
Encyclopedia
Solifenacin 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
.
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
.hk
, gastric retention, uncontrolled or poorly controlled closed-angle glaucoma
, or severe liver disease (Child-Pugh
class C).
It is also contraindicated in long QT syndrome
, as solifenacin, like tolterodine
and darifenacin
, binds to HERG
channels
and may prolong the QT interval
.
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.
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
.
s of solifenacin are dry mouth, blurred vision, and constipation. As all anticholinergics, solifenacin may rarely cause heat prostration
due to decreased perspiration.
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.
Antispasmodic
An antispasmodic is a drug or a herb that suppresses muscle spasms.-Smooth muscle spasm:One type of antispasmodics is used for smooth muscle contraction, especially in tubular organs of the gastrointestinal tract...
of the antimuscarinic class. It is used in the treatment of overactive bladder
Overactive bladder
Overactive bladder is a urological condition defined by a set of symptoms: urgency, with or without urge incontinence, usually with frequency and nocturia. Frequency is usually defined as urinating more than 8 times a day. The International Continence Society is responsible for this definition...
with or without urge incontinence. It is manufactured by Astellas and co-marketed by Astellas and GlaxoSmithKline
GlaxoSmithKline
GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...
.
Mechanism of action
Solifenacin is a competitiveCompetitive antagonist
A competitive antagonist is a receptor antagonist that binds to a receptor but does not activate the receptor. The antagonist will compete with available agonist for receptor binding sites on the same receptor...
muscarinic acetylcholine receptor
Muscarinic acetylcholine receptor
Muscarinic receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled in the plasma membranes of certain neurons and other cells...
antagonist
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
. The binding of acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
to these receptors, particularly the M3 receptor subtype, plays a critical role in the contraction of smooth muscle
Smooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...
.
By preventing the binding of acetylcholine to these receptors, solifenacin reduces smooth muscle tone
Muscle tone
In physiology, medicine, and anatomy, muscle tone is the continuous and passive partial contraction of the muscles, or the muscle’s resistance to passive stretch during resting state. It helps maintain posture, and it declines during REM sleep.-Purpose:Unconscious nerve impulses maintain the...
in the bladder
Urinary bladder
The urinary bladder is the organ that collects urine excreted by the kidneys before disposal by urination. A hollow muscular, and distensible organ, the bladder sits on the pelvic floor...
, 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
Urinary bladder
The urinary bladder is the organ that collects urine excreted by the kidneys before disposal by urination. A hollow muscular, and distensible organ, the bladder sits on the pelvic floor...
smooth muscle
Smooth muscle
Smooth muscle is an involuntary non-striated muscle. It is divided into two sub-groups; the single-unit and multiunit smooth muscle. Within single-unit smooth muscle tissues, the autonomic nervous system innervates a single cell within a sheet or bundle and the action potential is propagated by...
tone
Muscle tone
In physiology, medicine, and anatomy, muscle tone is the continuous and passive partial contraction of the muscles, or the muscle’s resistance to passive stretch during resting state. It helps maintain posture, and it declines during REM sleep.-Purpose:Unconscious nerve impulses maintain the...
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Contraindications
Solifenacin should not be taken by people with a history of previous hypersensitivity to it, urinary retentionUrinary retention
Urinary retention, also known as ischuria, is a lack of ability to urinate. It is a common complication of benign prostatic hyperplasia , although it can also be caused by nerve dysfunction, constipation, infection, or medications...
, gastric retention, uncontrolled or poorly controlled closed-angle glaucoma
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
, or severe liver disease (Child-Pugh
Child-Pugh score
In medicine , the Child-Pugh score is used to assess the prognosis of chronic liver disease, mainly cirrhosis...
class C).
It is also contraindicated in long QT syndrome
Long QT syndrome
The long QT syndrome is a rare inborn heart condition in which delayed repolarization of the heart following a heartbeat increases the risk of episodes of torsade de pointes . These episodes may lead to palpitations, fainting and sudden death due to ventricular fibrillation...
, as solifenacin, like tolterodine
Tolterodine
Tolterodine is an antimuscarinic drug that is used to treat urinary incontinence.It is marketed by Pfizer in Canada and the United States by its brand name Detrol. In Egypt it is also found under the trade names Tolterodine by Sabaa and Incont L.A...
and darifenacin
Darifenacin
Darifenacin is a medication used to treat urinary incontinence. It used to be marketed by Novartis; however in 2010 US rights for were sold to Warner Chilcott for 400 million US$....
, binds to HERG
HERG
hERG is a gene that codes for a protein known as Kv11.1 potassium ion channel...
channels
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
and may prolong the QT interval
QT interval
In cardiology, the QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. In general, the QT interval represents electrical depolarization and repolarization of the left and right ventricles...
.
Interactions
Solifenacin is metabolized in the liver by the cytochrome P450Cytochrome P450 oxidase
The cytochrome P450 superfamily is a large and diverse group of enzymes. The function of most CYP enzymes is to catalyze the oxidation of organic substances. The substrates of CYP enzymes include metabolic intermediates such as lipids and steroidal hormones, as well as xenobiotic substances...
enzyme CYP3A4
CYP3A4
Cytochrome P450 3A4 , a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body. CYP3A4 is involved in the oxidation of the largest range of substrates of all the CYPs. As a result, CYP3A4 is present in...
. When administered concomitantly with drugs that inhibit CYP3A4, such as ketoconazole
Ketoconazole
Ketoconazole is a synthetic antifungal drug used to prevent and treat fungal skin infections, especially in immunocompromised patients such as those with AIDS or those on chemotherapy. Ketoconazole is sold commercially as an anti-dandruff shampoo, topical cream, and oral tablet.Ketoconazole is...
, 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.
As stated above, solifenacin may also prolong the QT interval
QT interval
In cardiology, the QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. In general, the QT interval represents electrical depolarization and repolarization of the left and right ventricles...
. Therefore, it should not be administered concomitantly with drugs which also have this effect, such as moxifloxacin
Moxifloxacin
Moxifloxacin is a fourth-generation synthetic fluoroquinolone antibacterial agent developed by Bayer AG . It is marketed worldwide under the brand names Avelox, Avalox, and Avelon for oral treatment. In most countries, the drug is also available in parenteral form for intravenous infusion...
or pimozide
Pimozide
Pimozide is an antipsychotic drug of the diphenylbutylpiperidine class. It was discovered at Janssen Pharmaceutica in 1963. It has a high potency compared to chlorpromazine . On a weight basis it is even more potent than haloperidol. It also has special neurologic indications for Tourette syndrome...
.
Side effects
The most common side effectAdverse drug reaction
An adverse drug reaction is an expression that describes harm associated with the use of given medications at a normal dosage. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs...
s of solifenacin are dry mouth, blurred vision, and constipation. As all anticholinergics, solifenacin may rarely cause heat prostration
Hyperthermia
Hyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate...
due to decreased perspiration.
Pharmacoeconomics
A 2006 cost-effectivenessCost-effectiveness
Cost-effectiveness analysis is a form of economic analysis that compares the relative costs and outcomes of two or more courses of action. Cost-effectiveness analysis is distinct from cost-benefit analysis, which assigns a monetary value to the measure of effect...
study found that 5 mg solifenacin had the lowest cost and highest effectiveness among anticholinergic
Anticholinergic
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....
drugs used to treat overactive bladder
Overactive bladder
Overactive bladder is a urological condition defined by a set of symptoms: urgency, with or without urge incontinence, usually with frequency and nocturia. Frequency is usually defined as urinating more than 8 times a day. The International Continence Society is responsible for this definition...
in the United States, with an average medical cost per successfully treated patient of $6863 per year.