Usage
Alfuzosin + Solifenacin is prescribed for the treatment of moderate to severe lower urinary tract symptoms (LUTS) in men associated with both benign prostatic hyperplasia (BPH) and overactive bladder (OAB).
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Pharmacological Classification:
- Alfuzosin: Alpha-1 adrenergic receptor blocker
- Solifenacin: Muscarinic receptor antagonist (anticholinergic)
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Mechanism of Action: This combination therapy targets two distinct mechanisms involved in LUTS. Alfuzosin relaxes the smooth muscle in the prostate and bladder neck, reducing urethral resistance and improving urine flow. Solifenacin decreases bladder contractions and the urge to urinate by blocking muscarinic receptors in the bladder detrusor muscle.
Alternate Names
- Vesomni (common brand name)
- Solitral (brand name in some regions)
- Alfuzosin + Solifenacin Succinate (generic name using succinate salt)
How It Works
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Pharmacodynamics: Alfuzosin, an alpha-1 blocker, primarily acts by relaxing the smooth muscle of the prostate and bladder neck, reducing urinary obstruction. Solifenacin, a competitive muscarinic receptor antagonist, acts predominantly on M3 receptors in the bladder, inhibiting involuntary detrusor contractions, thus decreasing urgency and frequency of urination.
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Pharmacokinetics:
- Alfuzosin: Alfuzosin is well-absorbed orally, reaching peak plasma concentration within approximately 8 hours. It is extensively metabolized in the liver, primarily by CYP3A4 enzymes. It is excreted mainly in feces and to a lesser extent in urine, with a half-life of 5-10 hours.
- Solifenacin: Solifenacin is also well-absorbed orally, with peak plasma levels attained in 3-8 hours. It undergoes extensive metabolism in the liver, primarily via CYP3A4. It is excreted in both urine and feces, having an elimination half-life of 45-68 hours.
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Receptor Binding/Enzyme Inhibition: Alfuzosin binds to alpha-1 adrenergic receptors, blocking the action of norepinephrine, leading to smooth muscle relaxation. Solifenacin competes with acetylcholine for binding at muscarinic M3 receptors, inhibiting cholinergic stimulation of bladder contractions.
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Elimination Pathways: Both alfuzosin and solifenacin are primarily metabolized in the liver, with a significant role played by CYP3A4. Both drugs are eliminated via both renal and hepatic routes.
Dosage
Standard Dosage
Children: Alfuzosin + Solifenacin is not recommended for use in children, as safety and efficacy have not been established. Solifenacin alone is approved for pediatric use in certain cases of neurogenic detrusor overactivity, but always refer to the latest pediatric guidelines.
Special Cases:
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Elderly Patients: No specific dosage adjustment is recommended solely based on age, but caution is warranted due to potential increased sensitivity to adverse effects like dizziness and orthostatic hypotension.
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Patients with Renal Impairment:
- Mild to moderate impairment (CrCl ≥ 30 mL/min): No dose adjustment.
- Severe impairment (CrCl < 30 mL/min): Solifenacin dose should not exceed 5 mg daily. Alfuzosin dose adjustment may be necessary. Consult specific guidelines for alfuzosin dosing in renal impairment.
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Patients with Hepatic Dysfunction:
- Mild impairment (Child-Pugh A): No dose adjustment.
- Moderate impairment (Child-Pugh B): Solifenacin dose should not exceed 5 mg daily. Alfuzosin dose adjustment may be necessary. Consult specific guidelines for alfuzosin dosing in hepatic impairment.
- Severe impairment (Child-Pugh C): Not recommended.
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Patients with Comorbid Conditions: Exercise increased caution in patients with cardiovascular diseases, especially QT prolongation, and other conditions potentially worsened by anticholinergic effects.
Clinical Use Cases
Alfuzosin + Solifenacin is not typically used in settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations. It is primarily indicated for the chronic management of BPH/OAB symptoms. Patients scheduled for surgery may need to discontinue therapy preoperatively, as per their surgeon’s instructions.
Dosage Adjustments
Dosage adjustments may be necessary based on individual patient response and tolerance. Close monitoring for adverse effects is essential, especially for patients with renal or hepatic impairment, cardiovascular disease, and those on interacting medications.
Side Effects
Common Side Effects:
- Dizziness
- Headache
- Tiredness
- Dry mouth
- Blurred vision
- Constipation
- Flushing
Rare but Serious Side Effects:
- Angioedema
- Anaphylaxis
- QT interval prolongation
- Urinary retention
- Severe constipation/intestinal obstruction
- Worsening of narrow-angle glaucoma
Long-Term Effects: Limited data exists on long-term effects, but careful monitoring for potential adverse events is essential.
Contraindications
- Hypersensitivity to alfuzosin or solifenacin.
- Urinary retention.
- Gastric retention.
- Uncontrolled narrow-angle glaucoma.
- Severe hepatic impairment (Child-Pugh C).
- Concomitant use with potent CYP3A4 inhibitors if not adjusting the dose.
- Use in women as it is for BPH.
Drug Interactions
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CYP450 Interactions: Both alfuzosin and solifenacin are metabolized by CYP3A4. Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir) may necessitate dose reductions or avoidance. CYP3A4 inducers (e.g., rifampin) can reduce drug levels.
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Other Interactions: Caution is advised when combining with other medications that prolong the QT interval, anticholinergic drugs, or alpha-blockers. Avoid or carefully monitor when using with certain antihypertensives, antifungals, and HIV protease inhibitors.
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Food/Lifestyle: Alcohol and grapefruit juice should be avoided or limited due to potential interactions.
Pregnancy and Breastfeeding
Alfuzosin + Solifenacin is not indicated for use in women and should be avoided during pregnancy and breastfeeding. Alfuzosin’s effect on pregnancy is unknown. Solifenacin excretion in breast milk is also unknown, and therefore, should not be used.
Drug Profile Summary
- Mechanism of Action: Alfuzosin: Alpha-1 blocker, relaxes smooth muscle. Solifenacin: Muscarinic antagonist, reduces bladder contractions.
- Side Effects: Dizziness, headache, tiredness, dry mouth, blurred vision, constipation.
- Contraindications: Hypersensitivity, urinary/gastric retention, glaucoma, severe liver disease, concomitant use with potent CYP3A4 inhibitors without dose adjustment. Use in women as it is for BPH.
- Drug Interactions: CYP3A4 inhibitors/inducers, QT prolonging agents, other anticholinergics, alpha-blockers.
- Pregnancy & Breastfeeding: Contraindicated. Not for use in women as it is used to treat men’s health conditions.
- Dosage: Adults: One tablet (10mg alfuzosin ER + 5 mg solifenacin IR) daily after the same meal.
- Monitoring Parameters: Blood pressure (for orthostatic hypotension), heart rate, ECG (for QT interval), liver and kidney function tests, symptoms of urinary retention.
Popular Combinations
Alfuzosin + Solifenacin itself represents a clinically relevant combination for managing BPH/OAB. Combining with other drugs requires careful consideration of potential interactions and benefits.
Precautions
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General Precautions: Assess renal and hepatic function, cardiac status, and history of glaucoma before starting treatment. Monitor for anticholinergic and orthostatic effects.
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Specific Populations: See “Special Cases” under Dosage.
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Lifestyle Considerations: Advise patients to limit alcohol, avoid driving or operating heavy machinery if experiencing dizziness or drowsiness.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Alfuzosin + Solifenacin?
A: One tablet (10 mg alfuzosin extended-release + 5 mg solifenacin immediate-release) once daily after the same meal each day.
Q2: Can Alfuzosin + Solifenacin be used in women?
A: No. This medication is specifically for men with BPH and OAB.
Q3: What are the most common side effects?
A: Dizziness, headache, tiredness, dry mouth, blurred vision, constipation.
Q4: Are there any serious side effects to watch out for?
A: Yes. Although rare, serious side effects can include angioedema, QT prolongation, urinary retention, and severe anticholinergic effects.
Q5: What should I advise my patient about taking this medication?
A: Take it after the same meal each day, avoid alcohol and grapefruit juice, be cautious when driving or operating machinery, report any severe or bothersome side effects.
Q6: How do I adjust the dose for a patient with renal impairment?
A: For mild to moderate renal impairment (CrCl ≥ 30 mL/min), no dose adjustment is usually needed. In severe renal impairment (CrCl < 30 mL/min), the solifenacin dose should not exceed 5 mg daily, and the alfuzosin dose may need to be adjusted. Consult alfuzosin prescribing information for specific recommendations.
Q7: What are the key drug interactions?
A: Strong CYP3A4 inhibitors, QT prolonging agents, anticholinergic drugs, and alpha-blockers can interact.
Q8: Can this combination be used with other BPH medications like 5-alpha reductase inhibitors?
A: Concomitant use is possible but must be done cautiously. Evaluate the potential benefits and risks for each patient individually.
Q9: What are the contraindications to using this combination?
A: Hypersensitivity to the components, urinary or gastric retention, uncontrolled narrow-angle glaucoma, severe liver disease, and concomitant use with potent CYP3A4 inhibitors without dose adjustment.
Q10: How does this medication affect blood pressure?
A: Alfuzosin can cause orthostatic hypotension, especially early in treatment. Monitor blood pressure closely and advise patients to be careful when changing positions.
