Usage
- Mirabegron + Silodosin is prescribed for the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) complicated by overactive bladder (OAB) in adult men. This includes symptoms such as urinary frequency, urgency, nocturia (frequent nighttime urination), and weak urine stream.
- Pharmacological classification: Urological agent, combination drug (beta-3 adrenergic agonist + alpha-1A adrenergic antagonist)
- Mechanism of action: Mirabegron, a beta-3 adrenergic agonist, relaxes the detrusor muscle of the bladder, increasing bladder capacity and reducing OAB symptoms. Silodosin, an alpha-1A adrenergic antagonist, relaxes the smooth muscle in the prostate and bladder neck, improving urinary flow and reducing BPH symptoms.
Alternate Names
- No widely recognized alternate names exist for the combination product itself. The individual components are sometimes referred to as mirabegron hydrochloride and silodosin hydrochloride.
- Brand names: Silodosia M, Silotrif M, Sildoo M.
How It Works
- Pharmacodynamics: Mirabegron increases bladder capacity by stimulating beta-3 adrenergic receptors in the detrusor muscle. Silodosin decreases urethral resistance by selectively blocking alpha-1A adrenergic receptors in the prostate, bladder neck, and prostatic urethra.
- Pharmacokinetics: Both drugs are orally administered. Mirabegron reaches peak plasma concentrations within 3-4 hours and has a half-life of approximately 50 hours. Silodosin reaches peak plasma concentrations within 4-6 hours and has a half-life of around 11 hours.
- Mode of action: Receptor binding (Mirabegron - beta-3 adrenergic receptor agonist, Silodosin - alpha-1A adrenergic receptor antagonist).
- Elimination pathways: Both drugs are extensively metabolized in the liver, primarily by CYP3A4 (Silodosin) and multiple pathways including CYP2D6 (Mirabegron), with subsequent renal excretion.
Dosage
Standard Dosage
Adults:
- Mirabegron 25 mg + Silodosin 8 mg orally once daily with a meal. Mirabegron may be increased to 50 mg once daily after 4-8 weeks if needed.
Children:
- Not recommended for use in children under 18 years of age.
Special Cases:
- Elderly Patients: No dose adjustment is typically required, but caution is advised due to potential age-related decline in renal and hepatic function.
- Patients with Renal Impairment: Moderate renal impairment (CrCl 30-89 mL/min): Reduce silodosin dose to 4 mg daily. Severe renal impairment (CrCl < 30 mL/min): Contraindicated. Mirabegron dose reduction may be considered in severe renal impairment (eGFR 15-29 mL/min) to 25mg once daily. End Stage renal dysfunction: Contraindicated.
- Patients with Hepatic Dysfunction: Moderate hepatic impairment (Child-Pugh B): Reduce mirabegron dose to 25 mg daily. Severe hepatic impairment (Child-Pugh C): Contraindicated.
- Patients with Comorbid Conditions: Use with caution in patients with uncontrolled hypertension, cardiovascular disease, or QT prolongation.
Clinical Use Cases
- Not indicated for use in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
- Dose adjustments may be necessary in patients with renal or hepatic impairment.
Side Effects
Common Side Effects:
- Dizziness, headache, nausea, constipation, urinary tract infections, nasopharyngitis, increased heart rate, abnormal ejaculation, retrograde ejaculation, nasal congestion, fatigue, dry mouth, dyspareunia.
Rare but Serious Side Effects:
- Atrial fibrillation (Mirabegron), severe hypotension, angioedema, allergic reactions (Silodosin), urinary retention.
Long-Term Effects:
- Limited data are available on long-term effects.
Adverse Drug Reactions (ADR):
- Angioedema, severe hypotension, atrial fibrillation, QT prolongation, and allergic reactions.
Contraindications
- Hypersensitivity to mirabegron or silodosin.
- Severe renal impairment (CrCl < 30 mL/min).
- Severe hepatic impairment (Child-Pugh C).
- Concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin).
- Use in women, including during pregnancy and breastfeeding.
Drug Interactions
- Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin): Increase silodosin levels.
- CYP2D6 inhibitors: May increase mirabegron levels.
- Antipsychotics (thioridazine), antiarrhythmics (propafenone, flecainide), tricyclic antidepressants (desipramine, imipramine), alpha-blockers (doxazosin, prazosin): Potential additive hypotensive effects.
Pregnancy and Breastfeeding
- Contraindicated in pregnancy and breastfeeding. Mirabegron is not recommended in women of childbearing potential not using contraception.
Drug Profile Summary
- Mechanism of Action: Mirabegron: Beta-3 adrenergic agonist; Silodosin: Alpha-1A adrenergic antagonist.
- Side Effects: Dizziness, headache, nausea, increased blood pressure, abnormal ejaculation.
- Contraindications: Severe renal or hepatic impairment, hypersensitivity.
- Drug Interactions: Strong CYP3A4 inhibitors, CYP2D6 substrates.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 25 mg/8 mg once daily, may increase to 50 mg/8 mg.
- Monitoring Parameters: Blood pressure, heart rate, renal and liver function.
Popular Combinations
Precautions
- Monitor blood pressure, particularly during initiation of therapy.
- Patients with moderate renal or hepatic impairment: Reduce dose and monitor closely.
- Caution in patients with cardiovascular disease or QT prolongation.
- Avoid activities requiring alertness if dizziness occurs.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Mirabegron + Silodosin?
A: The recommended starting dosage is Mirabegron 25 mg + Silodosin 8 mg orally once daily with a meal. The Mirabegron dose can be increased to 50 mg once daily if needed after 4-8 weeks.
Q2: What are the common side effects?
A: Common side effects include dizziness, headache, nausea, increased heart rate, abnormal ejaculation, and nasal congestion.
Q3: Is Mirabegron + Silodosin safe for patients with liver disease?
A: It is contraindicated in patients with severe hepatic impairment. Use with caution and a reduced dose in moderate hepatic impairment.
Q4: Can women take Mirabegron + Silodosin?
A: No, this medication is contraindicated in women, including during pregnancy and breastfeeding.
Q5: What should patients do if they miss a dose?
A: Take the missed dose as soon as remembered, unless it is almost time for the next dose. Do not double the dose.
Q6: Does Mirabegron + Silodosin interact with other medications?
A: Yes, it can interact with strong CYP3A4 inhibitors, CYP2D6 substrates, and certain antihypertensive medications. Consult a physician regarding concurrent medication usage.
Q7: What are the serious side effects to watch for?
A: Atrial fibrillation, severe hypotension, angioedema, allergic reactions, and urinary retention are rare but serious side effects.
Q8: Can patients drink alcohol while taking Mirabegron + Silodosin?
A: The interaction with alcohol is unknown. Caution is advised. It is recommended to discuss alcohol consumption with a physician.
Q9: What if a patient experiences dizziness after taking Mirabegron + Silodosin?
A: Patients should avoid driving or operating machinery if they experience dizziness. They should also avoid sudden changes in posture and inform their doctor.
