Solifenacin is a medication primarily used to treat overactive bladder symptoms, such as frequent or urgent urination and urinary incontinence. It belongs to a class of medications known as antimuscarinics or anticholinergics, which work by blocking certain receptors in the bladder muscles, thereby reducing bladder contractions and helping to control symptoms.

Overactive bladder (OAB) is a condition characterized by a sudden, involuntary contraction of the muscle in the wall of the bladder, leading to symptoms such as frequent urination, urgency to urinate, and sometimes urinary incontinence.

Solifenacin helps to relax the bladder muscles, which can decrease the frequency of urination, reduce urgency, and improve bladder control. It is typically taken orally in the form of tablets or extended-release capsules.

Solifenacin (Vesicare) is an antimuscarinic drug that is used to treat patients with symptoms of overactive bladder manifesting as urgency, frequency, and urinary incontinence.

Solifenacin Uses:

• Overactive bladder:
  • Treatment of overactive bladder with symptoms of increased urinary frequency, urgency, and/or urge incontinence.

Solifenacin (Vesicare) Dose in Adults

Solifenacin (Vesicare) Dose in the treatment of Overactive bladder:

• When taken by mouth, the starting dose is 5 mg once a day. If you can handle it well, the doctor might increase it to 10 mg once a day.
• If you're taking other strong medications that affect how your body processes solifenacin, like ketoconazole, the maximum dose you should take is 5 mg per day.

Solifenacin (Vesicare) Dose in Childrens

Not recommended for use in children.

Pregnancy Risk Factor C

• Solifenacin is classified as Pregnancy Risk Factor C, which means there may be a risk to the fetus based on animal studies, but there are limited human studies available.
• Adverse events were observed in some animal reproduction studies, indicating potential risks to the fetus if the medication is used during pregnancy.

Solifenacin use during breastfeeding:

• Solifenacin's presence in breast milk is not well understood.
• The manufacturer advises making a decision between discontinuing breastfeeding or discontinuing the drug, as there is uncertainty about the potential risks to the nursing infant.

Vesicare Dose in Kidney Disease:

• For individuals with a Creatinine Clearance (CrCl) of 30 mL/minute or higher, no specific dosage adjustments are mentioned in the manufacturer's instructions. However, caution is advised when using solifenacin in this population.
• If someone's CrCl is less than 30 mL/minute, the maximum recommended dose of solifenacin is 5 mg per day. This lower dose is suggested because their kidneys may not be able to clear the medication from the body as efficiently as those with higher CrCl levels, potentially increasing the risk of side effects.

Vesicare Dose in Liver disease:

• In individuals with mild impairment according to the Child-Pugh classification (Class A), no dosage adjustment is needed for solifenacin. However, it's advised to use the medication with caution.
• For those with moderate impairment (Class B), the maximum recommended dose is 5 mg per day.
• For individuals with severe impairment (Class C), solifenacin use is not recommended due to the potential risks associated with reduced liver function.

Common Side Effects of Solifenacin (Vesicare):

• Gastrointestinal:
  • Xerostomia
  • Constipation

Less Common Side Effects of Vesicare:

• Cardiovascular:
  • Hypertension
  • Lower Extremity Edema
• Central Nervous System:
  • Fatigue
  • Depression
• Gastrointestinal:
  • Dyspepsia
  • Nausea
  • Upper Abdominal Pain
  • Vomiting
• Genitourinary:
  • Urinary Tract Infection
  • Urinary Retention
• Ophthalmic:
  • Blurred Vision
  • Dry Eye Syndrome
• Respiratory:
  • Cough
• Miscellaneous:
  • Influenza

Contraindications to Solifenacin (Vesicare):

Solifenacin is contraindicated in individuals who have:

• Hypersensitivity to solifenacin or any ingredient in the formulation.
• Urinary retention, a condition where you can't empty your bladder completely.
• Gastric retention, a condition where food stays in the stomach for too long.
• Uncontrolled narrow-angle glaucoma, a type of eye condition.

Additionally, in Canadian labeling, solifenacin is contraindicated in individuals undergoing dialysis.

Warnings and precautions

Angioedema

• Solifenacin can cause angioedema, which is swelling under the skin, often occurring in the face, lips, tongue, or throat.
• Some people may experience this even after their first dose, and it can be life-threatening.
• If swelling involves the tongue, throat, or larynx, it's crucial to stop taking the medication immediately and seek medical help for supportive care.

CNS effects

• Solifenacin can have effects on the central nervous system (CNS), such as headaches, confusion, hallucinations, and drowsiness.
• It's essential to keep an eye out for these effects, especially when starting treatment or increasing the dose.
• If needed, the dose can be lowered or the medication stopped altogether.
• Solifenacin might also cause drowsiness and blurred vision, which can affect a person's ability to perform tasks requiring mental alertness, like operating machinery or driving.
• Patients should be cautioned about these potential effects.

Heat prostration:

• Solifenacin can increase the risk of heat prostration, especially in hot weather or during exercise.
• Heat prostration is when the body overheats due to high temperatures, leading to symptoms like dehydration, heat exhaustion, or even heatstroke.
• It's important to be cautious when exposed to hot environments or engaging in physical activities while taking solifenacin.

Hypersensitivity reactions

• Rarely, hypersensitivity reactions, including anaphylactic reactions, have been reported with solifenacin use.
• Anaphylactic reactions are severe and can be life-threatening, involving symptoms such as difficulty breathing, swelling of the face or throat, and a sudden drop in blood pressure.
• If such a reaction occurs, it's crucial to stop taking solifenacin immediately and seek emergency medical attention.

Alzheimer disease

• Preliminary research indicates that long-term use of anticholinergic medications like solifenacin might have negative effects on the progression of Alzheimer's disease, especially in patients also taking cholinesterase inhibitors for their dementia.
• Studies suggest that such dual therapy could potentially worsen cognitive function, daily functioning, and behavioral issues in individuals with dementia.
• Therefore, extra monitoring is recommended for changes in cognition, functional abilities, and problematic behaviors in patients with dementia who are receiving both a cholinesterase inhibitor and a bladder anticholinergic medication like solifenacin.

Bladder outflow obstruction

• Solifenacin should be used cautiously in patients with bladder outflow obstruction, such as benign prostatic hyperplasia (BPH).
• In such individuals, there's a risk that solifenacin might increase the likelihood of urinary retention, where the bladder isn't able to empty completely.
• Therefore, close monitoring is advised when using solifenacin in patients with bladder outflow obstruction.

Gastrointestinal Disease:

• Solifenacin should be used cautiously in patients with gastrointestinal (GI) conditions that affect GI motility, such as severe constipation or ulcerative colitis, or those with GI obstructive disorders like pyloric stenosis.
• In such cases, there's a risk that solifenacin may increase the chance of gastric retention, where food stays in the stomach for too long.
• Therefore, extra caution is advised when prescribing solifenacin to patients with these GI conditions.

Glaucoma:

• Solifenacin should be used cautiously in patients with controlled (treated) narrow-angle glaucoma.
• However, it's important to note that solifenacin is contraindicated in individuals with uncontrolled narrow-angle glaucoma.
• This means that while it can be used in patients with controlled narrow-angle glaucoma, extra caution is necessary, and it should not be used in those with uncontrolled narrow-angle glaucoma due to the potential risk of worsening the condition.

Hepatic impairment

• Solifenacin should be used cautiously in patients with moderate hepatic impairment, which is classified as Child-Pugh class B.
• In such cases, dosage adjustment may be necessary.
• However, solifenacin use is not recommended in patients with severe hepatic impairment, classified as Child-Pugh class C.
• This means that in individuals with severe impairment, the medication should generally be avoided due to the potential risks associated with reduced liver function.

Extension of QT

• Solifenacin should be used cautiously in patients with a known history of QT prolongation or other risk factors for QT prolongation, such as concomitant use of medications known to prolong the QT interval or electrolyte abnormalities.
• The risk of QT prolongation with solifenacin is related to the dosage, so it's important to monitor patients closely, especially if they have any of these risk factors.

Renal impairment

• Solifenacin should be used cautiously in patients with renal impairment.
• Dosage adjustment is necessary for individuals with severe renal impairment, defined as a Creatinine Clearance (CrCl) less than 30 mL/minute.
• This means that the dose of solifenacin needs to be adjusted in these patients to ensure safe and effective treatment.

Solifenacin: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy).
Acetylcholinesterase inhibitors	Anticholinergic Agents may have a decreased therapeutic effect. Anticholinergic Agents can decrease the therapeutic effects of Acetylcholinesterase inhibitors.
Amantadine	Anticholinergic Agents may have an enhanced anticholinergic effect.
Anticholinergic Agents	Other Anticholinergic Agents may have an adverse/toxic effect.
Aprepitant	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Bosentan	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Botulinum Toxin-Containing Products	Anticholinergic Agents may have an enhanced anticholinergic effect.
Cannabinoid-Containing Products	Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Cannabidiol is an exception.
Chloral Betaine	Anticholinergic Agents may have an adverse/toxic effect.
Clofazimine	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Moderate CYP3A4 Inducers	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Moderate CYP3A4 inhibitors	Might decrease metabolism of CYP3A4 substrates (High Risk with Inhibitors).
Deferasirox	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Duvelisib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Erdafitinib	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Erdafitinib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Fosaprepitant	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Fosnetupitant	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Gastrointestinal Agents (Prokinetic)	Anticholinergic Agents can reduce the therapeutic effects of Gastrointestinal Agents (Prokinetic).
Glucagon	Anticholinergic agents may increase the toxic/adverse effects of Glucagon. Particularly, there may be an increase in the likelihood of gastrointestinal adverse reactions.
Haloperidol	QT-prolonging agents (Indeterminate risk - Caution), may increase the QTcprolonging effects of Haloperidol.
Itopride	Itopride's therapeutic effects may be diminished by anticholinergic agents.
Ivosidenib	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Larotrectinib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Mianserin	Anticholinergic Agents may have an enhanced anticholinergic effect.
Mirabegron	Could increase the toxic/adverse effects of Solifenacin. In particular, acute urinary retention risk may be increased.
Netupitant	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Nitroglycerin	The absorption of Nitroglycerin may be decreased by anticholinergic agents. Anticholinergic Agents may reduce the dissolution sublingual nitroglycerin tablet, which could impair or slow down nitroglycerin absorbtion. Opioid Agonists - Anticholinergic agents may increase the toxic/adverse effects of Opioid Agonists. This combination may increase the risk of constipation or urinary retention.
Palbociclib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
QT-prolonging agents (Highest risk)	QT-prolonging agents (Indeterminate risk - Caution), may increase the QTc prolonging effect of QT Prolonging Agents. When using these agents together, be sure to monitor for QTc interval prolongation or ventricular arrhythmias. Patients at higher risk for QTc prolongation might have additional risk factors.
Ramosetron	Ramosetron's constipating effects may be enhanced by anticholinergic agents.
Sarilumab	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Siltuximab	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Simeprevir	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Thiazide and Thiazide -Like Diuretics	Anticholinergic Agents can increase serum Thiazide or Thiazide-Like Diuretics.
Tocilizumab	Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers).
Topiramate	Topiramate's toxic/adverse effects may be exacerbated by anticholinergic agents.
Risk Factor D (Regard therapy modification)
Strong CYP3A4 Inducers	May increase metabolism of CYP3A4 substrates (High Risk with Inducers). Management: You may consider a different drug to replace one of the interacting drugs. Some combinations might be contraindicated. Consult appropriate manufacturer labeling.
Strong CYP3A4 inhibitors	Increased serum levels of Solifenacin may occur. Management: Solifenacin should be taken in small doses, no more than 5 mg per day when used with strong CYP3A4 inhibitors.
Dabrafenib	High risk of Inducers causing a decrease in serum CYP3A4 substrates. Management: If possible, seek alternatives to the CYP3A4 substrate. Concomitant therapy should be avoided if possible. Monitor the clinical effects of the substrate carefully (especially therapeutic effects).
Enzalutamide	High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Management: Avoid concurrent use of enzalutamide and CYP3A4 substrates with a narrow therapeutic index. You should exercise caution when using enzalutamide or any other CYP3A4 sub-substance.
Itraconazole	Increased serum concentrations of Solifenacin may occur. Itraconazole and solifenacin should be used together only at 5 mg per day. Patients with severe renal impairment or moderate to severe liver impairment should not take solifenacin with itraconazole.
Lorlatinib	High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Management: Do not use lorlatinib concurrently with any CYP3A4 Substrates. Even a slight decrease in serum concentrations could cause therapeutic failure or serious clinical consequences.
MiFEPRIStone	High risk of Inhibitors causing an increase in serum concentrations of CYP3A4 substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid dihydroergotamine and ergotamine.
Mitotane	High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Treatment: Patients receiving mitotane may require significant adjustments in the dosage of CYP3A4 Substrates.
Pramlintide	Anticholinergic Agents may have an enhanced anticholinergic effect. These effects are only for the GI tract.
Secretin	Secretin's therapeutic effects may be diminished by anticholinergic agents. Concomitant use: Secretin and anticholinergic agents should be avoided. Stop using anticholinergic drugs for at least five half-lives before administering secretin.
St John's Wort	High risk of Inducers causing a decrease in serum CYP3A4 Substrates. Management: You may consider a different drug to replace one of the interacting drugs. Some combinations might be contraindicated. Consult appropriate manufacturer labeling.
Stiripentol	High risk of Inhibitors causing an increase in serum concentrations of CYP3A4 substrates. Management: Avoid stiripentol use with CYP3A4 Substrates that have a narrow therapeutic Index. This is to avoid adverse effects and toxicities. Monitoring of any CYP3A4 substrate that is used with stiripentol should be closely done.
Risk Factor X (Avoid Combination)
Aclidinium	Anticholinergic Agents may have an enhanced anticholinergic effect.
Cimetropium	Cimetropium may have an anticholinergic effect that can be enhanced by the use of anticholinergic agents.
Conivaptan	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Eluxadoline	Eluxadoline may cause constipation by using anticholinergic agents.
Fusidic Acid (Systemic).	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Glycopyrrolate (Oral Inhalation)	Anticholinergic agents may increase the anticholinergic effects of Glycopyrrolate (Oral inhalation).
Glycopyrronium (Topical)	Anticholinergic Agents may have an enhanced anticholinergic effect.
Idelalisib	High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations
Oral Inhalation with Ipratropium	Anticholinergic Agents may have an enhanced anticholinergic effect.
Levosulpiride	Anticholinergic Agents can reduce the therapeutic effects of Levosulpiride.
Oxatomide	Anticholinergic Agents may have an enhanced anticholinergic effect.
Potassium Chloride	Potassium Chloride may have an ulcerogenic effect that can be exacerbated by anticholinergic agents. Treatment: Patients taking drugs that have significant anticholinergic effects should not consume any oral dose form of potassium chloride.
Potassium Citrate	Potassium Citrate may be more ulcerogenic if it is given to anticholinergic agents.
Revefenacin	Revefenacin may be enhanced by anticholinergic agents.
Tiotropium	Anticholinergic agents may increase the anticholinergic effects of Tiotropium.
Umeclidinium	Anticholinergic Agents may have an enhanced anticholinergic effect.

Monitoring parameters:

Anticholinergic Effects

• Solifenacin can cause various anticholinergic effects, including:
  • Headache
  • Confusion
  • Hallucinations
  • Drowsiness
  • Fixed and dilated pupils
  • Blurred vision
  • Tremors
  • Dry skin

Creatinine Clearance

• Solifenacin use requires consideration of creatinine clearance, especially in patients with kidney impairment.

Hepatic Function

• Caution is advised when using solifenacin in patients with liver problems.

Post-void Residuals in BPH Therapy

• When solifenacin is added to alpha-blocker therapy for benign prostatic hyperplasia (BPH), it's important to monitor post-void residuals, which is the amount of urine left in the bladder after urination.

How to administer Solifenacin (Vesicare)?

• Solifenacin should be taken with water, regardless of meals.
• It should be swallowed whole and not crushed or chewed.

Mechanism of action of Solifenacin (Vesicare):

Solifenacin works by blocking muscarinic receptors, which leads to several effects in the urinary bladder:

• Decreased urinary bladder contraction: By blocking these receptors, solifenacin reduces the involuntary contractions of the bladder muscle.
• Increased residual urine volume: This medication can cause the bladder to retain more urine after urination.
• Decreased detrusor muscle pressure: The detrusor muscle is a muscle layer in the bladder wall. Solifenacin helps relax this muscle, reducing the pressure within the bladder.

Distribution:

• The volume of distribution (V) is approximately 600 liters, indicating that solifenacin is widely distributed throughout the body.

Protein Binding:

• Solifenacin is highly bound to plasma proteins, primarily to alpha-acid glycoprotein, with around 98% binding.

Metabolism:

• It undergoes extensive hepatic metabolism, primarily via pathways involving CYP3A4 enzymes. Metabolism produces one active and three inactive metabolites.

Bioavailability:

• Solifenacin has high oral bioavailability, estimated to be around 90%.

Half-life:

• The elimination half-life of solifenacin ranges from 45 to 68 hours with chronic dosing.
• This half-life can be prolonged in severe renal impairment or moderate hepatic impairment.

Time to peak plasma concentration:

• Solifenacin reaches peak plasma concentration 3 to 8 hours after administration.

Excretion:

• The primary route of excretion is through urine, with approximately 69.2% of the dose excreted this way, with less than 15% as unchanged drug. About 22.5% of the dose is excreted in feces.

International Brands of Solifenacin:

• VESIcare
• ACT-Solifenacin
• APO-Solifenacin
• Auro-Solifenacin
• JAMP-Solifenacin
• MED-Solifenacin
• MINT-Solifenacin
• PMS-Solifenacin
• RAN-Solifenacin
• SANDOZ Solifenacin
• TEVA-Solifenacin
• VESIcare
• Asolfena
• Bispec
• Slowurge
• Sofcare
• Solficare
• Solicin
• Soliten
• Somfen
• Tormeel
• Urisol
• Utrobin
• Vesicare
• Vesiker
• Vesikur
• Vesitrim
• Vesizen
• Zevesin

Solifenacin Brand Names in Pakistan:

Solifenacin succinate 5 mg Tablets
Fenaso	Highnoon Laboratories Ltd.
Solcina	Helix Pharma (Private) Limited
Solicon	Efroze Chemical Industries (Pvt) Ltd.
Solifen	Getz Pharma Pakistan (Pvt) Ltd.
Vesiwel	Ray Pharma (Pvt) Ltd

 

Solifenacin 10 mg Tablets
Fenaso	Highnoon Laboratories Ltd.
Solicon	Efroze Chemical Industries (Pvt) Ltd.
Solifen	Getz Pharma Pakistan (Pvt) Ltd.
Vesiwel	Ray Pharma (Pvt) Ltd