Usage
Silodosin + Solifenacin is prescribed for the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and overactive bladder (OAB) in men. This combination therapy addresses both storage and voiding issues. Silodosin is highly selective for the alpha-1A adrenergic receptors in the prostate, bladder base, bladder neck, and prostatic urethra and is used to treat symptoms of BPH. Solifenacin improves the symptoms of OAB.
Pharmacological Classification:
- Silodosin: Alpha-1A adrenergic receptor antagonist.
- Solifenacin: Muscarinic receptor antagonist (anticholinergic).
Mechanism of Action:
Silodosin relaxes the smooth muscle in the prostate and bladder neck, improving urine flow and reducing bladder outlet obstruction. Solifenacin inhibits the action of acetylcholine on muscarinic receptors in the bladder, reducing bladder contractions and the urge to urinate.
Alternate Names
While there isn’t a universally recognized international nonproprietary name for this combination product, the individual components are recognized as silodosin and solifenacin succinate.
Brand Names: SILODOSIA SF, Vesomni (solifenacin and tamsulosin).
How It Works
Pharmacodynamics: Silodosin selectively blocks alpha-1A adrenoreceptors in the lower urinary tract, leading to smooth muscle relaxation and improved urine flow. Solifenacin competitively binds to muscarinic receptors, particularly M3 subtypes, in the bladder, inhibiting involuntary detrusor contractions.
Pharmacokinetics: Silodosin reaches peak plasma concentration approximately 1 hour after oral administration with food. Solifenacin peaks at 3–8 hours post-dose. Both drugs are metabolized primarily by the liver (CYP3A4) and excreted in the urine and feces. The elimination half-life of silodosin is around 6 hours, while it is between 45 to 68 hours for solifenacin.
Mode of Action:
- Silodosin: Receptor binding (alpha-1A adrenoreceptor antagonist).
- Solifenacin: Receptor binding (competitive muscarinic receptor antagonist).
Elimination Pathways: Both are primarily hepatically metabolized by CYP3A4 with renal and fecal excretion.
Dosage
Standard Dosage
Adults:
One capsule of Silodosin 8 mg + Solifenacin 5 mg once daily, taken with a meal.
Children:
This combination is not recommended for pediatric use. Solifenacin has pediatric dosing guidelines based on weight for monotherapy, but the combination has not been studied in children.
Special Cases:
- Elderly Patients: No dose adjustment is typically necessary. Close monitoring is recommended.
- Patients with Renal Impairment: For moderate renal impairment (CrCl 30–50 mL/min), the silodosin component may be initiated at 4 mg and increased to 8 mg after a week if tolerated. For severe renal impairment (CrCl < 30 mL/min), silodosin + solifenacin is not recommended. Solifenacin should not exceed 5 mg daily for severe renal impairment.
- Patients with Hepatic Dysfunction: For moderate hepatic impairment (Child-Pugh B), solifenacin should not exceed 5 mg once daily. The combination is contraindicated in severe hepatic impairment.
- Patients with Comorbid Conditions: Use with caution in patients with diabetes, cardiovascular disease, or narrow-angle glaucoma.
Clinical Use Cases
Silodosin + Solifenacin is not indicated for use in clinical settings such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dose adjustments may be required based on individual patient tolerance and clinical response, specifically focusing on renal or hepatic function. Concomitant use of strong CYP3A4 inhibitors necessitates a reduction in the solifenacin dose to 5 mg daily.
Side Effects
Common Side Effects
- Dizziness
- Dry mouth
- Constipation
- Retrograde ejaculation
- Blurred vision
- Headache
- Nasal congestion
Rare but Serious Side Effects
- Angioedema
- Anaphylaxis
- Urinary retention
- Severe hypotension
- Liver dysfunction
Long-Term Effects
Long-term effects are largely unknown, though chronic complications related to anticholinergic use, such as cognitive impairment, are possible with solifenacin.
Adverse Drug Reactions (ADR)
Significant ADRs requiring immediate intervention include angioedema, anaphylaxis, and severe hypotension.
Contraindications
- Hypersensitivity to either component
- Urinary retention
- Gastric retention
- Uncontrolled narrow-angle glaucoma
- Severe hepatic impairment (Child-Pugh C)
- Use with potent CYP3A4 inhibitors (for higher solifenacin doses)
Drug Interactions
- CYP3A4 Inhibitors (ketoconazole, itraconazole): May increase solifenacin levels. Reduce solifenacin dosage to 5 mg daily.
- Anticholinergic Agents: Additive anticholinergic effects. Use with caution.
- Alpha-blockers: May enhance hypotensive effects of silodosin.
- Alcohol: May increase dizziness and other side effects.
Pregnancy and Breastfeeding
Silodosin is not indicated for use in women. Solifenacin should generally be avoided during pregnancy and breastfeeding due to limited safety data. It is classified as Pregnancy Category C in the US FDA categories (old system) – meaning that risk cannot be ruled out. If used during breastfeeding, monitor the infant for potential anticholinergic effects.
Drug Profile Summary
- Mechanism of Action: Silodosin: Alpha-1A blocker. Solifenacin: Muscarinic antagonist.
- Side Effects: Dizziness, dry mouth, constipation, retrograde ejaculation, blurred vision.
- Contraindications: Urinary retention, gastric retention, narrow-angle glaucoma, severe hepatic impairment.
- Drug Interactions: CYP3A4 inhibitors, anticholinergic agents, alpha-blockers.
- Pregnancy & Breastfeeding: Avoid if possible, limited data. Solifenacin is present in breast milk.
- Dosage: 8 mg silodosin + 5 mg solifenacin once daily with a meal.
- Monitoring Parameters: Blood pressure, liver function tests, post-void residual volume, and symptoms.
Popular Combinations
This combination is frequently used for concurrent BPH and OAB. It’s crucial to consider individual patient response and tailor the dosage and combination accordingly.
Precautions
Screen patients for pre-existing conditions like renal/hepatic impairment, narrow-angle glaucoma, or urinary retention. Patients using this combination should be cautious operating machinery or driving due to potential dizziness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Silodosin + Solifenacin?
A: The standard dosage is 8 mg silodosin + 5 mg solifenacin once daily with a meal.
Q2: Can this combination be used in women?
A: No. Silodosin is only indicated for use in men. Solifenacin can be used in women, but not in combination with silodosin.
Q3: What are the most common side effects?
A: Dizziness, dry mouth, constipation, retrograde ejaculation, and blurred vision are common side effects.
Q4: Are there any serious side effects?
A: Yes. Though rare, serious side effects include angioedema, anaphylaxis, urinary retention, severe hypotension, and liver dysfunction.
Q5: How does this medication work in BPH?
A: Silodosin relaxes smooth muscle in the prostate and bladder neck, improving urine flow.
Q6: How does this medication work in OAB?
A: Solifenacin reduces bladder contractions and the urge to urinate.
Q7: Are there any drug interactions I should be aware of?
A: Yes. Avoid using it with strong CYP3A4 inhibitors like ketoconazole. Use caution with other anticholinergics or alpha-blockers.
Q8: Can I take this medication if I have kidney problems?
A: It depends on the severity. Dose adjustments are needed for moderate renal impairment, and it’s not recommended for severe renal impairment.
Q9: Can this medicine be taken with or without food?
A: It should be taken with food to improve absorption and reduce gastrointestinal side effects.
