Solifenacin succinate: Salt form of the M3 selective antagonist solifenacin
Solifenacin succinate is the salt form of the active ingredient solifenacin used in all pharmaceutical preparations, an M3 muscarinic receptor selective antagonist for the treatment of overactive bladder. Known brand names are Vesicare (Astellas) and numerous generics. Solifenacin was approved in Europe in 2004 and today belongs together with tolterodine, fesoterodine, darifenacin and mirabegron to the standard therapy for overactive bladder. A detailed pillar page on the active ingredient can be found at /wirkstoff/solifenacin.
The salt form succinate (succinic acid salt) was chosen because it provides good water solubility and stability. In the body, the salt dissociates immediately into the active solifenacin and succinate, so the effect is carried exclusively by solifenacin.
Mechanism of action and salt form
Solifenacin is a competitive antagonist at the muscarinic M3 receptor with significantly higher selectivity versus M1, M2 and M5 subtypes. The M3 receptor is the predominant contractile receptor in the detrusor muscle of the bladder. Its blockade reduces spontaneous and reflex detrusor activity, increases functional bladder capacity and reduces urgent urination.
The M3 selectivity of solifenacin theoretically reduces side effects mediated by other muscarinic receptor subtypes, especially tachycardia (M2 in cardiac muscle) and cognitive effects (M1 in the central nervous system). In clinical practice, however, the selectivity is not absolute, anticholinergic side effects such as dry mouth and constipation continue to occur.
Pharmacokinetically, solifenacin succinate is well absorbed orally (bioavailability approximately 90 percent), half-life 45 to 68 hours, which allows once daily administration. Metabolism in the liver via CYP3A4. Elimination renal after conjugation.
Indications
- Overactive bladder (OAB): Symptoms of urgent urination, urinary frequency, urgency incontinence
- Neurogenic bladder overactivity: after stroke, in multiple sclerosis, Parkinson's disease, spinal cord injury
- Pediatric age: Solifenacin is approved in some indications from 2 years of age for neurogenic detrusor hyperactivity, with Pediatric Investigation Plan
Dosage and administration
Adults: Initial dose 5 mg once daily, if response is inadequate increase to 10 mg after 4 weeks.
In renal insufficiency with eGFR below 30 ml/min: Maximum dose 5 mg daily. In moderate liver insufficiency: Maximum dose 5 mg daily. In severe liver insufficiency and severe renal insufficiency with hemodialysis: contraindicated.
Administration: with or without food, preferably at the same time of day. Consistent intake is important for uniform drug levels and effect.
Therapeutic success: First improvement usually within 1 to 2 weeks, full effect after 8 to 12 weeks.
Side effects
Very common (anticholinergic): Dry mouth (most common side effect, approximately 30 percent), constipation, vision disorders (accommodation disorder), dry eyes, nausea.
Common: Fatigue, dizziness, headache, urinary retention especially in men with prostatic hyperplasia, confusion particularly in elderly patients, tachycardia (less than with non-selective anticholinergics).
Rare: Acute angle-closure glaucoma, Stevens Johnson syndrome, allergic reactions, anaphylaxis, paralytic ileus.
Important, anticholinergic burden: Solifenacin contributes to the so-called anticholinergic load, which is associated with cognitive decline, dementia and fall risk. Especially in elderly patients and in polypharmacy, the indication should be reviewed regularly, alternative therapies such as mirabegron are a non-anticholinergic option.
Drug interactions
- Other anticholinergic drugs (tricyclic antidepressants, diphenhydramine, atropine): Additive anticholinergic burden
- Cholinesterase inhibitors (donepezil, galantamine, rivastigmine): Mutual cancellation of effects
- Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, HIV protease inhibitors): Increased solifenacin levels, maximum dose 5 mg
- Strong CYP3A4 inducers (rifampicin, phenytoin, carbamazepine, St. John's wort): Reduced solifenacin levels
- QT prolonging drugs (sotalol, amiodarone, erythromycin, some antidepressants): Additive QT prolongation
- Alcohol: Enhances fatigue and cognitive effects
Special precautions
Pregnancy and breast-feeding: Data limited, use only after strict indication. If needed, behavioral measures and pelvic floor training are preferred during pregnancy.
Angle-closure glaucoma: Solifenacin can increase intraocular pressure and is contraindicated in untreated angle-closure glaucoma. Before starting therapy, counsel on warning symptoms (acute eye pain, red eye, vision impairment, headache, nausea).
Urinary retention: Patients with post-void residual or urinary bladder emptying disorder should be evaluated urologically before therapy, in men residual urine measurement and prostate assessment.
QT prolongation: Solifenacin at higher doses can prolong the QT interval. Caution in pre-existing QT prolongation, hypokalemia or concurrent therapy with QT prolonging drugs.
Driving ability: Solifenacin can cause blurred vision, dizziness and fatigue, which may impair driving ability.
You might also be interested in
- Solifenacin, detailed pillar page on the active ingredient
- Tolterodine, another muscarinic receptor antagonist
- Fesoterodine, prodrug to 5HMT
- Mirabegron, beta-3 adrenergic receptor agonist as non-anticholinergic alternative
- Oxybutynin, older anticholinergic
Frequently asked questions
What is the advantage of solifenacin over tolterodine?
Solifenacin is relatively selective for the M3 receptor, which mediates bladder contraction. This selectivity theoretically reduces side effects on the heart (tachycardia via M2) and cognitive function (via M1). In practice, however, the tolerability of both substances is similar, individual differences between patients can be more relevant than the theoretical selectivity.
How quickly does solifenacin work?
First improvements are often noticeable after 1 to 2 weeks, full effect develops over 8 to 12 weeks. If response is inadequate after 4 weeks, the dose can be increased to 10 mg, if response continues to be inadequate, switching to another active ingredient or mirabegron should be considered.
What can I do about dry mouth?
Frequent drinking of small amounts of water, sugar-free candies or chewing gum, artificial saliva as spray or gel, careful oral hygiene to prevent caries and thrush. If dry mouth is unbearable, switching to mirabegron, which does not work anticholinergically, may be appropriate.
Can I take solifenacin in early dementia?
Anticholinergics can worsen cognitive symptoms, the risk of dementia increases with long-term use. In patients with dementia or under cholinesterase inhibitor therapy, solifenacin should be avoided if possible, alternatively mirabegron is an option as a non-anticholinergic alternative.
Sources
- EMA, Vesicare (solifenacin succinate) EPAR
- DGU S2k guideline overactive bladder
- Gelbe Liste, solifenacin active ingredient profile
- BfArM, Federal Institute for Drugs and Medical Devices
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