Solifenacin, sold as the brand name Vesicare among others, is a medication used to treat overactive bladder and neurogenic detrusor overactivity (NDO). It may help with incontinence, urinary frequency, and urinary urgency. 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. Severe side effects may include urinary retention, QT prolongation, hallucinations, glaucoma, and anaphylaxis. It is unclear if use is safe during pregnancy. It is of the antimuscarinic class and works by decreasing bladder contractions. Solifenacin was approved for medical use in the United States in 2004. In 2023, it was the 245th most commonly prescribed medication in the United States, with more than 1 million prescriptions.
Medical uses It is used to treat overactive bladder. It may help with incontinence, urinary frequency, and urinary urgency. Benefits appear similar to other antimuscarinics such as oxybutynin, tolterodine, 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 urinary retention, gastric retention, uncontrolled or poorly controlled closed-angle glaucoma, severe liver disease (Child-Pugh class C), and hemodialysis. 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. 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 effects of solifenacin are dry mouth, constipation and urinary tract infection. As all anticholinergics, solifenacin may rarely cause hyperthermia due to decreased perspiration. 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 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. 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.
Pharmacology
Mechanism of action Solifenacin is a competitive cholinergic receptor antagonist, selective for the M3 receptor subtype. However, it is said to also act as an antagonist of the other four muscarinic acetylcholine receptors. 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.
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 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.
Chemistry 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.
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