Alfuzosin
Alfuzosin
Generic Name
Alfuzosin
Mechanism
- Alfuzosin is a selective α1-adrenergic receptor antagonist.
- It preferentially blocks α1A‑ and α1B‑receptors in the smooth muscle of the prostate, bladder neck, and lower urinary tract.
- By inhibiting adrenergic stimulation, it reduces urethral and prostatic smooth‑muscle tone, thereby improving urine flow and decreasing bladder outlet obstruction.
- Its high receptor selectivity results in minimal vascular α1 antagonism, limiting orthostatic hypotension compared with older α‑blockers.
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Pharmacokinetics
| Parameter | Typical Value | Notes |
| Absorption | Rapid, peak plasma conc. 1–2 h post‑dose | Food decreases Cmax slightly but clinical effect unchanged |
| Distribution | Moderate; 65–70 % protein‑bound (albumin and alpha‑1‑acid glycoprotein) | Limited CNS penetration |
| Metabolism | Hepatic via CYP3A4 (first‑pass) | Conjugated metabolites excreted unchanged |
| Elimination | Primarily renal (≈45 %) and fecal (≈35 %) | Half‑life ~5 h (inter‑individual 5–7 h) |
| Drug Interactions | Strong CYP3A4 inhibitors (e.g., ketoconazole) ↑ plasma levels; rifampin ↓ levels | Avoid concomitant high‑dose diuretics that increase fall risk |
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Indications
- Benign prostatic hyperplasia (BPH)
- *Improves micturition symptoms*: urinary flow rate ↑, post‑void residual ↓.
- Typically prescribed for men ≥40 years with moderate‑to‑severe lower urinary tract symptoms due to BPH.
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Contraindications
- Contraindications
- Severe hepatic impairment (Child‑Pugh C).
- Known hypersensitivity to alfuzosin or other α1‑blockers.
- Concomitant use with a potent CYP3A4 inhibitor that may cause significant QT prolongation.
- Warnings
- Orthostatic hypotension: especially first dose; monitor BP before and 30 min post‑dose.
- Drug–drug interactions: avoid combining with nitrates, diuretics, or antihypertensives that lower BP.
- Pregnancy: category B; use only if benefit outweighs risk.
- Renal or hepatic adjustments: no dose change needed for mild to moderate dysfunction; avoid in severe cases.
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Dosing
- Adults: 10 mg orally once daily in the evening, 30 min after a meal.
- Maintain *constant* dosing schedule; avoid missing doses for >2 days.
- Adjustment: Not required for mild‑moderate hepatic or renal impairment.
- Titration: If inadequate response, consider adding 2 mg/day titration increments after 4 weeks (max 12 mg/day).
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Adverse Effects
| Adverse Effect | Frequency | Notes |
| Dizziness/orthostatic hypotension | 5–10 % | First‑dose phenomenon; counsel patients on slow standing. |
| Headache | ≤4 % | Usually mild. |
| Postural dizziness | ≤3 % | May indicate autonomic dysfunction. |
| Erythema, flushing | <2 % | Transient. |
| Serious | ||
| QTc prolongation | Rare | Use caution if concomitant QT‑prolonging drugs. |
| Syncope | Very rare | Related to hypotensive episodes. |
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Monitoring
| Parameter | Target / Frequency |
| Blood pressure | Baseline; 30 min post‑dose; then every 4 weeks until stable. |
| HbA1c in diabetics | Yearly; monitor if concomitant metformin. |
| Renal & hepatic panels | Every 3–6 months for patients >65 yrs or with comorbidity. |
| Symptomatic assessment | International Prostate Symptom Score (IPSS) at baseline, 6‑8 weeks, then every 6 months. |
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Clinical Pearls
- First‑Day Dip: Educate patients that the first dose is most likely to cause orthostatic hypotension—stand slowly, sit for 5–10 min, and consider a “split dose” (5 mg at bedtime, 5 mg 30 min pre‑bed) if severe.
- Food Interaction Simplicity: Unlike some α1‑blockers, food only marginally delays absorption; continue with meals to reduce GI upset.
- Fixed‑Dose Strategy: For most BPH patients, maintain 10 mg daily for 4–6 weeks before considering dose escalation.
- Combination Therapy: Alfuzosin does not synergize with 5α‑reductase inhibitors at the receptor level; add finasteride separately only for refractory BPH to address gland size.
- Non‑BPH Use: Despite approvals, alfuzosin has limited evidence for detrusor overactivity; avoid off‑label prescription absent clinical trial data.
- Rapid Discontinuation Warning: Abruptly stopping alfuzosin can precipitate rebound urinary retention; taper over 1–2 weeks if discontinuation necessary.
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