Usage
Solifenacin is prescribed for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency. It is also used to treat neurogenic detrusor overactivity (NDO) in children two years and older. It is pharmacologically classified as a competitive muscarinic receptor antagonist, specifically targeting the M3 subtype. Solifenacin works by blocking the action of acetylcholine at these receptors in the bladder, reducing detrusor muscle contractions and thus improving bladder control.
Alternate Names
Solifenacin succinate is the chemical name. Vesicare is a popular brand name.
How It Works
Pharmacodynamics: Solifenacin exhibits competitive antagonism at muscarinic M3 receptors, which are highly expressed in the bladder. This competitive inhibition leads to a reduction in involuntary detrusor muscle contractions. Solifenacin exhibits some selectivity for M3 receptors compared to other muscarinic subtypes however other muscarinic receptors can also be targeted with higher solifenacin concentrations, potentially leading to side effects.
Pharmacokinetics:
- Absorption: Solifenacin is rapidly absorbed after oral administration, reaching peak plasma concentrations within 3 to 8 hours. Food does not significantly affect absorption.
- Metabolism: Primarily metabolized in the liver via CYP3A4, with minor contributions from other CYP enzymes.
- Elimination: Excreted through both renal (approximately 60%) and hepatic (approximately 20%) pathways, with a terminal elimination half-life of 45-68 hours.
Dosage
Standard Dosage
Adults:
The recommended starting dose is 5 mg orally once daily. If tolerated well, the dose may be increased to 10 mg orally once daily.
Children (for Neurogenic Detrusor Overactivity):
Dosing is based on body weight and should be administered using the 1 mg/mL oral suspension:
- 9-15 kg: 2 mL (2 mg) orally once daily, not to exceed 4 mL (4 mg) daily
- >15-30 kg: 3 mL (3 mg) orally once daily, not to exceed 5 mL (5 mg) daily
- >30-45 kg: 3 mL (3 mg) orally once daily, not to exceed 6 mL (6 mg) daily
- >45-60 kg: 4 mL (4 mg) orally once daily, not to exceed 8 mL (8 mg) daily
- >60 kg: 5 mL (5 mg) orally once daily, not to exceed 10 mL (10 mg) daily
Special Cases:
- Elderly Patients: No dosage adjustment is generally necessary. However, close monitoring for side effects is advisable.
- Patients with Renal Impairment:
- Mild to moderate (CrCl ≥ 30 mL/min): No dosage adjustment is necessary.
- Severe (CrCl < 30 mL/min): Maximum dose of 5 mg once daily.
- Patients with Hepatic Dysfunction:
- Mild (Child-Pugh A): No dosage adjustment necessary.
- Moderate (Child-Pugh B): Maximum dose of 5 mg once daily.
- Severe (Child-Pugh C): Not recommended.
- Patients with Comorbid Conditions: Caution should be exercised in patients with gastrointestinal conditions, narrow-angle glaucoma, or those at risk for QT prolongation.
Clinical Use Cases
Solifenacin is not typically indicated for use in clinical situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary use is for managing chronic OAB symptoms and NDO.
Dosage Adjustments
For patients on potent CYP3A4 inhibitors (e.g., ketoconazole, ritonavir), the maximum dose of solifenacin should be limited to 5 mg once daily.
Side Effects
Common Side Effects:
Dry mouth, constipation, blurred vision, urinary tract infection, dyspepsia, and headache.
Rare but Serious Side Effects:
Angioedema, anaphylaxis, acute urinary retention, severe allergic reactions, and QT interval prolongation.
Long-Term Effects:
Potential long-term effects may include chronic dry mouth, constipation, and potential for cognitive impairment with anticholinergic use, although this requires further investigation.
Adverse Drug Reactions (ADR):
Clinically significant ADRs include urinary retention, angle-closure glaucoma, and severe allergic reactions requiring immediate medical attention.
Contraindications
- Urinary retention
- Gastric retention
- Uncontrolled narrow-angle glaucoma
- Myasthenia gravis
- Severe hepatic impairment (Child-Pugh C)
- Patients undergoing hemodialysis
- Hypersensitivity to solifenacin or its components
Drug Interactions
Solifenacin is primarily metabolized by CYP3A4. Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir, itraconazole) can increase solifenacin plasma levels and should be avoided or the solifenacin dose should be reduced. CYP3A4 inducers (e.g., rifampin) may decrease solifenacin efficacy.
Concomitant use with other anticholinergic drugs may exacerbate anticholinergic side effects. Caution should be exercised when co-administering solifenacin with drugs known to prolong the QT interval.
Pregnancy and Breastfeeding
Solifenacin is classified as Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit outweighs the potential risk to the fetus. It is unknown whether solifenacin is excreted in human milk. Caution should be exercised when administering to breastfeeding women.
Drug Profile Summary
- Mechanism of Action: Competitive muscarinic M3 receptor antagonist.
- Side Effects: Dry mouth, constipation, blurred vision, urinary retention.
- Contraindications: Urinary retention, gastric retention, narrow-angle glaucoma, myasthenia gravis.
- Drug Interactions: CYP3A4 inhibitors and inducers, other anticholinergics.
- Pregnancy & Breastfeeding: Category C; use with caution.
- Dosage: 5 mg orally once daily, may increase to 10 mg if tolerated.
- Monitoring Parameters: Monitor for urinary retention, intraocular pressure (IOP), and anticholinergic side effects.
Popular Combinations
Solifenacin is sometimes used in combination with tamsulosin for the treatment of OAB in men with benign prostatic hyperplasia (BPH).
Precautions
- Pre-existing conditions like glaucoma, myasthenia gravis, and gastrointestinal disorders should be assessed before initiating therapy.
- Caution in elderly patients due to increased risk of cognitive impairment and other anticholinergic side effects.
- Monitor patients for urinary retention.
- Avoid driving or operating heavy machinery if experiencing blurred vision or dizziness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Solifenacin?
A: The standard adult dosage is 5 mg once daily, which can be increased to 10 mg if tolerated. Pediatric dosing for NDO varies depending on body weight, starting from 2 mg daily for children weighing 9-15 kg.
Q2: What are the common side effects of Solifenacin?
A: Common side effects include dry mouth, constipation, blurred vision, and urinary tract infections.
Q3: How does Solifenacin work?
A: Solifenacin is a competitive muscarinic receptor antagonist, selectively targeting M3 receptors in the bladder to reduce involuntary detrusor muscle contractions.
Q4: Who should not take Solifenacin?
A: Patients with urinary retention, gastric retention, uncontrolled narrow-angle glaucoma, myasthenia gravis, or severe hepatic impairment should not take Solifenacin.
Q5: What are the serious side effects of Solifenacin?
A: Angioedema, anaphylaxis, severe allergic reactions, QT prolongation, and acute urinary retention are potential serious side effects.
Q6: Are there any drug interactions with Solifenacin?
A: Yes, strong CYP3A4 inhibitors and inducers can affect solifenacin levels. Co-administration with other anticholinergic medications may exacerbate side effects.
Q7: Can Solifenacin be used during pregnancy or breastfeeding?
A: Solifenacin is a pregnancy category C drug. Its safety during pregnancy and breastfeeding has not been established. Use with caution only if the potential benefit outweighs the potential risk.
Q8: What should patients be monitored for while taking Solifenacin?
A: Patients should be monitored for urinary retention, changes in IOP, and other anticholinergic side effects like dizziness, confusion, or cognitive impairment.
Q9: What is the difference between solifenacin and solifenacin succinate?
A: Solifenacin succinate is the salt form of solifenacin, which is the active compound used to treat OAB. Solifenacin succinate is more stable and easier to formulate into tablets or oral suspension.
Q10: How long does it take for solifenacin to start working?
A: Some patients might experience improvement in their symptoms within a week, while others may take up to 4 weeks or longer to see any noticeable changes.
