Mirabegron
Mirabegron
Generic Name
Mirabegron
Mechanism
- Selective β₃‑adrenergic stimulation of bladder detrusor smooth muscle → ↑ cyclic‑AMP → detrusor relaxation.
- Increases maximal bladder capacity (MBC) and inter‑void intervals without affecting bladder compliance.
- Minimal cross‑reactivity with α‑ or β₁/β₂‑receptors, reducing tachycardia or orthostatic hypotension compared to non‑selective agents.
Pharmacokinetics
| Parameter | Key Points |
| Absorption | Oral bioavailability ~50 %; delayed absorption (peak 4–6 h). |
| Distribution | Protein–binding ~61 %; volume of distribution ~20 L/kg. |
| Metabolism | Primarily CYP2D6, CYP2C19, and CYP3A4 mediated. Metabolites inactive; minor CYP2C19 contribution. |
| Elimination | Renal excretion (~70 %) and fecal (~20 %). Terminal half‑life: 20–35 h. |
| Drug interactions | Inhibitors/inducers of CYP2D6 or CYP3A4 alter clearance; caution with *nifedipine*, *sotalol*, *clopidogrel*, and *fluoxetine*. High‐dose *CYP2D6* inhibitors may increase levels by ~30 %. |
Indications
- Overactive bladder in adults (≥18 yrs) with urgency, frequency, urge‑incontinence, and/or nocturia.
- Adjunct or alternative when antimuscarinic therapy is contraindicated, poorly tolerated, or ineffective.
Contraindications
- Absolute contraindications: severe uncontrolled hypertension (SBP > 180 mmHg or DBP > 100 mmHg), pregnancy (category *D*).
- Relative cautions:
- Cardiovascular disease (ischemic heart disease, coronary artery disease, arrhythmias).
- Uncontrolled or severe hypertension—start at lowest dose.
- Concurrent β₃‑agonists (none approved).
- Renal impairment—dose adjustment in CrCl < 30 mL/min.
- Pediatric use: not approved.
Dosing
- Initial dose: 25 mg PO once daily (preferable for drug‑naïve patients).
- Titration: Increase to 50 mg PO once daily after 4 weeks if inadequate control.
- Maximum: 50 mg single daily dose (no need for split dosing).
- Administration: With or without food; take at same time each day.
- Missed dose: Skip; do not double dose next day.
Monitoring
- Blood pressure: baseline, at 1, 2, 4 weeks; thereafter annually.
- Heart rate & rhythm: baseline, 2 weeks, monthly in high‑risk patients.
- Renal function: CrCl at baseline and every 6 months (or more frequent if CrCl 150 mL.
- Symptom scores: OAB diaries, urgency episodes, incontinence episodes, nocturia frequency at baseline and every 4 weeks.
Clinical Pearls
1. “Headache first, hypertension later.” Headache is the most common early side effect; transient blood‑pressure spikes usually appear within the first 4 weeks and tend to resolve by week 8.
2. Use with caution in the elderly: age > 70 yrs and baseline hypertension double the risk for symptomatic tachycardia; consider starting at 25 mg.
3. Fixed‑dose pairing: Mirabegron’s long half‑life permits once‑daily dosing even at the 50 mg level—helps with adherence in patients with OAB.
4. Non‑anticholinergic benefit: avoids dry mouth, constipation, and cognitive decline seen with antimuscarinic drugs—valuable for cognitively impaired or poly‑pharmacy patients.
5. Renal dosing: In moderate renal impairment (CrCl 30–59 mL/min) no dose adjustment is needed, but monitor for safety; in severe renal impairment (< 30 mL/min) the use is not recommended.
6. Drug interactions matter: co‑administration with *fluoxetine* or *cimetidine* can raise mirabegron levels; adjust dose or monitor BP closely.
7. Pregnancy label: Category *D* – avoid if possible due to uncertain fetal safety.
8. No need for a washout period before switching from antimuscarinic agents—though symptoms may overlap initially.
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• Mirabegron offers a β₃‑agonist alternative for OAB with a favorable safety profile when appropriately monitored, making it an excellent choice for patients who cannot tolerate antimuscarinic side effects.