Doxazosin
Doxazosin
Generic Name
Doxazosin
Mechanism
- Competitive blockade of α1‑adrenergic receptors on vascular smooth muscle and prostate smooth muscle.
- Vasodilation reduces peripheral resistance → lower systolic and diastolic blood pressure.
- Relaxation of prostatic urethral smooth muscle decreases bladder outlet obstruction, improving urinary flow and symptoms.
Pharmacokinetics
- Absorption: Oral; peak plasma levels at ~1 h (BPH formulation) or 4–6 h (hypertension formulation).
- Bioavailability: ~60–70 % (well‑absorbed, no first‑pass metabolism).
- Distribution: Highly lipophilic; extensive tissue distribution, notably in vascular and prostatic tissues.
- Metabolism: Primarily hepatic via CYP3A4 (minor role of CYP2D6).
- Elimination: Excreted as metabolites through urine (≈70 %) and feces (≈25 %).
- Half‑life: ~22 h (BPH form); therapeutic plasma concentrations sustained for 24 h, permitting once‑daily dosing.
Indications
- Benign prostatic hyperplasia (BPH): Relief of lower urinary tract symptoms (LUTS) and prevention of acute urinary retention.
- Essential hypertension: Effective as monotherapy or combination therapy for adults.
Contraindications
- Contraindicated in:
- Severe hepatic impairment (due to CYP3A4 metabolism).
- Known hypersensitivity to any component.
- Warnings:
- *Orthostatic hypotension*—most common in the first 12 h after dosing.
- *Bradycardia/heart block* in combination with β‑blockers or other agents that lower heart rate.
- *Pregnancy:* Category C—use only if clearly needed.
- *Elderly:* Increased sensitivity—start at lower dose.
Dosing
| Condition | Starting Dose | Titration | Max Daily Dose | Form |
| BPH (oral suspension) | 1 mg daily | Increase by 1 mg every 2–4 weeks | Up to 8 mg | 1 mg tablets or 1 mg/mL oral suspension |
| BPH (tablet) | 1 mg daily | Increase by 1 mg every 2–4 weeks | Up to 4 mg | 1 mg tablets (also available 0.5 mg) |
| Hypertension | 1–2 mg daily | Increase by 1–2 mg weekly | Up to 12 mg | 1 mg, 2 mg, 4 mg tablets; 1 mg/mL oral suspension |
Administration Tips
• Take at bedtime to minimize orthostatic hypotension.
• Avoid abrupt discontinuation to prevent rebound hypertension.
Adverse Effects
Common (≥5 %)
• Headache, dizziness, flushing, nasal congestion.
• Orthostatic hypotension (first dose).
• Weakness, fatigue.
Serious (≤1 %)
• Severe hypotension or syncope.
• Reflex tachycardia (in susceptible patients).
• Angioedema (rare).
Drug Interactions
• Ketoconazole ↑ doxazosin levels (CYP3A4 inhibition).
• CYP3A4 inducers (e.g., rifampin, carbamazepine) ↓ efficacy.
• Diuretics, β‑blockers ↑ risk of hypotension.
Monitoring
- Baseline & periodic BP (sitting and standing).
- Heart rate (especially in combinations with β‑blockers).
- Renal & hepatic function before initiating therapy.
- Urinary flow rates and symptom scores for BPH patients.
Clinical Pearls
- Start low, go slow: In BPH, the first 2 weeks at 1 mg maximize safety; titrate only after stable urinary symptom relief.
- Bedtime dosing: Reduces first‑dose orthostatic hypotension; particularly important in elderly or hypertensive patients.
- Sodium adjustment: In hypertensive patients with fluid retention, advise sodium restriction to potentiate effect.
- Pregnancy considerations: Use only if benefits outweigh risks; consult obstetrician.
- Combination therapy: Pairing doxazosin with 5α‑reductase inhibitors (e.g., finasteride) in BPH can improve symptom control over monotherapy.
*References:*
• U.S. FDA prescribing information (Doxazosin, Tamsolin).
• UpToDate: *Alpha‑adrenergic antagonists for BPH and hypertension*.
• Goodman & Gilman’s *The Pharmacological Basis of Therapeutics*, 13th ed.