Usage
Mirabegron + Solifenacin is prescribed for the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency. It belongs to the pharmacological classifications of beta-3 adrenergic agonists (mirabegron) and muscarinic antagonists (solifenacin). Mirabegron works by relaxing the detrusor smooth muscle of the bladder, increasing bladder capacity. Solifenacin blocks M3 muscarinic receptors, inhibiting involuntary bladder contractions. The combination provides synergistic effects to improve OAB symptoms.
Alternate Names
Mirabegron is also known as Myrbetriq (brand name). Solifenacin is also known as Vesicare (brand name). The combination is often referred to as “Myrbetriq + Vesicare”.
How It Works
Pharmacodynamics: Mirabegron stimulates beta-3 adrenergic receptors in the bladder, causing relaxation of the detrusor muscle and increased bladder capacity. Solifenacin competitively binds to and blocks M3 muscarinic receptors in the bladder, reducing involuntary bladder contractions.
Pharmacokinetics:
- Mirabegron: It is well-absorbed after oral administration, reaching peak plasma concentrations in 3-4 hours. It is metabolized primarily by CYP2D6 and to a lesser extent by CYP3A4. Elimination is mainly via the urine and feces.
- Solifenacin: It is rapidly absorbed, reaching peak concentrations within 3-8 hours. It is metabolized by CYP3A4. Excretion is primarily through the urine and feces.
Mode of Action: Mirabegron acts on beta-3 adrenoceptors, a subtype of adrenergic receptor primarily located in the detrusor muscle of the bladder. Activation of these receptors leads to muscle relaxation and increased bladder filling. Solifenacin, an antimuscarinic agent, blocks the action of acetylcholine at M3 muscarinic receptors in the bladder. This reduces involuntary detrusor muscle contractions.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Mirabegron binds to beta-3 adrenergic receptors. Solifenacin competitively binds to M3 muscarinic receptors. Mirabegron inhibits CYP2D6, and Solifenacin is metabolized by CYP3A4.
Elimination Pathways: Mirabegron is mainly eliminated through a combination of renal excretion and hepatic metabolism involving CYP2D6 and CYP3A4. Solifenacin is primarily eliminated through hepatic metabolism via CYP3A4, with subsequent excretion through the urine.
Dosage
Standard Dosage
Adults:
The initial dose is Mirabegron 25 mg + Solifenacin 5 mg orally once daily. After 4-8 weeks, the Mirabegron dose can be increased to 50 mg once daily based on individual patient response and tolerability.
Children:
Mirabegron + Solifenacin is not recommended for use in children under 18 years of age. For pediatric use of Mirabegron alone in neurogenic detrusor overactivity, dosing is based on weight and age, specifically for children 3 years and older, and differs between tablet and granule formulation. Consultation with a pediatric specialist is recommended.
Special Cases:
- Elderly Patients: No dose adjustment is generally required.
- Patients with Renal Impairment: For severe renal impairment (eGFR 15-29 mL/min/1.73 m^2), the maximum dose of Mirabegron is 25 mg once daily. It’s not recommended for patients with end-stage renal disease (eGFR <15 mL/min/1.73 m^2 or on dialysis).
- Patients with Hepatic Dysfunction: For moderate hepatic impairment (Child-Pugh B), the maximum dose of Mirabegron is 25 mg once daily. It’s not recommended for patients with severe hepatic impairment (Child-Pugh C).
- Patients with Comorbid Conditions: Patients with uncontrolled hypertension or bladder outlet obstruction should be treated with caution.
Clinical Use Cases
The use of Mirabegron + Solifenacin in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations is not established and is not recommended.
Dosage Adjustments
Dose adjustments may be necessary in patients with renal or hepatic dysfunction as described above.
Side Effects
Common Side Effects
Dry mouth, constipation, headache, nausea, dizziness, urinary tract infection, increased blood pressure, tachycardia, blurred vision.
Rare but Serious Side Effects
Angioedema (swelling of face, lips, tongue, or throat), irregular heartbeat, urinary retention.
Long-Term Effects
Long-term effects have not been fully characterized, but they may include chronic dry mouth, constipation, and elevated blood pressure.
Adverse Drug Reactions (ADR)
Angioedema and severe hypertension.
Contraindications
Hypersensitivity to mirabegron or solifenacin, end-stage renal disease, severe hepatic impairment, gastric retention, uncontrolled narrow-angle glaucoma.
Drug Interactions
Mirabegron inhibits CYP2D6 and can increase the levels of drugs metabolized by this enzyme (e.g., metoprolol, thioridazine). Solifenacin is metabolized by CYP3A4. Concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole) or inducers (e.g., rifampin) might require dose adjustments. Concurrent use with other antimuscarinics may increase the risk of anticholinergic adverse effects. It is known to interact with some medications such as digoxin, some antifungals and antivirals and therefore should be used with caution.
Pregnancy and Breastfeeding
Mirabegron + Solifenacin should be used with caution during pregnancy and breastfeeding. The safety of this combination during pregnancy has not been established. Animal studies have shown some potential adverse effects on the fetus. Consult with a physician to assess the risk/benefit ratio before use. It is recommended to discuss any safer alternative treatments.
Drug Profile Summary
- Mechanism of Action: Mirabegron relaxes the bladder muscle, while Solifenacin blocks receptors that cause bladder contractions.
- Side Effects: Common: dry mouth, constipation, headache. Serious: angioedema, irregular heartbeat.
- Contraindications: Hypersensitivity, severe renal/hepatic impairment.
- Drug Interactions: CYP2D6 inhibitors, other antimuscarinics.
- Pregnancy & Breastfeeding: Use with caution. Discuss with a physician.
- Dosage: Initial: Mirabegron 25 mg + Solifenacin 5 mg once daily. May increase Mirabegron to 50 mg after 4-8 weeks.
- Monitoring Parameters: Blood pressure, heart rate, symptoms of urinary retention, liver function tests.
Popular Combinations
This drug itself is a combination medication frequently used in clinical practice for managing OAB symptoms. Other combinations are not typically recommended.
Precautions
- General Precautions: Assess for allergies, hypertension, bladder outlet obstruction, renal and hepatic function.
- Specific Populations: Use cautiously in pregnant/breastfeeding women, elderly patients, and those with renal/hepatic dysfunction. Consult a physician.
- Lifestyle Considerations: Limit alcohol consumption, as it may worsen dizziness. Caution should be exercised when driving or operating machinery.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Mirabegron + Solifenacin?
A: The recommended starting dosage is Mirabegron 25 mg + Solifenacin 5 mg once daily. After 4-8 weeks, the Mirabegron dose can be increased to 50 mg daily if needed.
Q2: What are the common side effects?
A: Common side effects include dry mouth, constipation, headache, urinary tract infection, and dizziness.
Q3: Is Mirabegron + Solifenacin safe for patients with renal impairment?
A: Dose adjustments are necessary for patients with renal impairment. It is not recommended for those with end-stage renal disease.
Q4: What are the contraindications for this combination?
A: Contraindications include hypersensitivity, end-stage renal disease, severe hepatic impairment, gastric retention, and uncontrolled narrow-angle glaucoma.
Q5: Can Mirabegron + Solifenacin be used during pregnancy?
A: It should be used with caution during pregnancy and only if the potential benefit outweighs the risks. Consult with a physician for advice.
Q6: How does this combination therapy work?
A: Mirabegron relaxes the bladder muscle, Solifenacin blocks nerve signals that cause bladder contractions.
Q7: What if I miss a dose?
A: Take the missed dose as soon as you remember, unless it’s almost time for the next dose. Do not double the dose.
Q8: What should patients be monitored for while taking Mirabegron + Solifenacin?
A: Blood pressure, heart rate, symptoms of urinary retention, and liver function should be monitored.
Q9: Are there any drug interactions I should be aware of?
A: Yes, Mirabegron can interact with other medications metabolized by CYP2D6, like certain beta-blockers or antidepressants. Solifenacin is metabolized by CYP3A4. Concurrent use with certain antifungals or antivirals might necessitate dose adjustments.
Q10: Can this drug combination be used in children?
A: Mirabegron + Solifenacin is not recommended for children under 18. Mirabegron alone has pediatric dosing guidelines for children 3 years and older with neurogenic detrusor overactivity. Consult a pediatric specialist.
