1. Medical use

2. Contraindications

3. Side effects

4. Interactions

5. Pharmacology
     Mechanism of action    Pharmacokinetics  

6. Chemistry

7. History

8. Society and culture
     Cost  

9. References

Common side effects include dry mouth and constipation.^[1] Severe side effects may include urinary retention, QT prolongation, hallucinations, and glaucoma.^[1][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.^[2] A month supply in the United Kingdom costs the NHS about 27.62 £ as of 2019.^[3] In the United States the wholesale cost of this amount is about 370 USD.^[4] In 2016 it was the 170th most prescribed medication in the United States with more than 3 million prescriptions.^[5]

Medical use

It is used to treat overactive bladder.^[2] It may help with incontinence, urinary frequency, and urinary urgency.^[3]

Benefits appear similar to other antimuscarinics such as oxybutynin, tolterodine, and darifenacin.^[1]

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),^[6] and hemodialysis.^[7]

Side effects

The most common side effects of solifenacin are dry mouth, blurred vision, and constipation. As all anticholinergics, solifenacin may rarely cause hyperthermia due to decreased perspiration.^[6]

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.^[6]

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.^[22]

Pharmacology

Mechanism of action

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.^[7]

Pharmacokinetics

Peak plasma concentrations are reached 3 to 8 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.^[7]

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.^[9]

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.^[10]

Society and culture

The INN is solifenacin.^[11] It is manufactured and marketed by Astellas, GlaxoSmithKline^[12] and Teva Pharmaceutical Industries.{{citation needed|date=December 2015}}

Cost

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.^[13]

References

• Soviet union dissolution
• Soviet union-east germany relations
• Soviet Union Fed Cup team
• Soviet union flag
• Soviet Union football league system
• Soviet Union in the Eurovision Song Contest
• Soviet Union in the Korean War
• Soviet Union in WWII
• Soviet Union-Japan relations
• Soviet Union men's national field hockey team
• Soviet Union-Mongolia relations
• Soviet Union National Anthem
• Soviet Union national field hockey team
• Soviet Union national field hockey team (disambiguation)
• Soviet Union national under-16 football team
• Soviet Union national under-17 football team
• Soviet Union national under-18 football team
• Soviet Union national under-18 ice hockey team
• Soviet Union national under-19 football team
• Soviet Union national under-20 football team
• Soviet Union national under-23 football team
• Soviet Union national under-23 football team (disambiguation)
• Soviet Union of Writers
• Soviet Union Olympic football team
• Soviet Union Premier Basketball League