Introduction
Doxazosin is a selective alpha-1 adrenergic receptor antagonist belonging to the quinazoline class of compounds. It is primarily used in the management of hypertension and benign prostatic hyperplasia (BPH). As a long-acting alpha-blocker, doxazosin provides sustained therapeutic effects with once-daily dosing, making it a convenient option for chronic management of these conditions.
Mechanism of Action
Doxazosin selectively and competitively blocks postsynaptic alpha-1 adrenergic receptors. In vascular smooth muscle, this blockade results in peripheral vasodilation, reducing peripheral vascular resistance and lowering blood pressure. In the prostate and bladder neck, alpha-1 receptor inhibition decreases smooth muscle tone, reducing urethral resistance and improving urinary flow in patients with BPH. The drug exhibits greater affinity for alpha-1 receptors than alpha-2 receptors, minimizing effects on presynaptic negative feedback mechanisms.
Indications
- Hypertension: Used alone or in combination with other antihypertensive agents
- Benign Prostatic Hyperplasia (BPH): Symptomatic treatment of urinary obstruction and related symptoms
- Off-label: Treatment of pheochromocytoma (in combination with alpha-blockers), Raynaud's phenomenon, and ureteral calculi passage
Dosage and Administration
Hypertension:- Initial dose: 1 mg once daily
- Maintenance dose: 1-16 mg once daily (dose titration every 1-2 weeks)
- Maximum dose: 16 mg daily
- Initial dose: 1 mg once daily
- Maintenance dose: 1-8 mg once daily
- Maximum dose: 8 mg daily
- Hepatic impairment: Use with caution; consider lower initial doses
- Renal impairment: No dosage adjustment required
- Geriatric patients: Initiate with 1 mg daily; titrate carefully
- Pediatric use: Safety and effectiveness not established
- Take with or without food
- Administer at bedtime to minimize first-dose effects
- Tablets should be swallowed whole, not crushed or chewed
Pharmacokinetics
Absorption: Well absorbed from GI tract with bioavailability approximately 65%. Food slightly delays absorption but does not affect overall bioavailability. Distribution: Highly protein-bound (98-99%), primarily to albumin. Volume of distribution is approximately 1-2 L/kg. Metabolism: Extensively metabolized in liver via O-demethylation and hydroxylation through CYP3A4 enzyme system. Elimination: Elimination half-life is 19-22 hours. Excreted primarily in feces (63%) and urine (9%) as metabolites. Less than 5% excreted unchanged.Contraindications
- Hypersensitivity to doxazosin, other quinazolines, or any component of the formulation
- Concurrent use with phosphodiesterase-5 inhibitors (for BPH treatment)
- Orthostatic hypotension
- Severe hepatic impairment
- Breastfeeding
Warnings and Precautions
First-dose Effect: Significant hypotension and syncope may occur within 2-6 hours of initial dose or dosage increases. Risk is minimized by starting with 1 mg dose and administering at bedtime. Orthostatic Hypotension: May occur, especially in volume-depleted patients or those taking other antihypertensive agents. Intraoperative Floppy Iris Syndrome: Has been reported during cataract surgery in patients taking alpha-blockers. Prostate Cancer: Should be ruled out before initiating treatment for BPH. Priapism: Rare cases reported; requires immediate medical attention. Hepatic Impairment: Use with caution due to extensive hepatic metabolism.Drug Interactions
Strong CYP3A4 Inhibitors: (ketoconazole, itraconazole, ritonavir) - May increase doxazosin concentrations Other Antihypertensive Agents: (beta-blockers, calcium channel blockers, diuretics) - Additive hypotensive effects Phosphodiesterase-5 Inhibitors: (sildenafil, tadalafil, vardenafil) - Contraindicated due to risk of severe hypotension NSAIDs: May reduce antihypertensive effect Estrogens: May decrease antihypertensive effect Sympathomimetics: May antagonize hypotensive effectsAdverse Effects
Common (≥1%):- Dizziness (15-19%)
- Fatigue (8-12%)
- Headache (5-8%)
- Orthostatic hypotension (0.3-4%)
- Edema (2-4%)
- Somnolence (3-4%)
- Nausea (2-3%)
- Syncope
- Severe orthostatic hypotension
- Priapism
- Angina pectoris
- Palpitations
- Hepatitis
- Leukopenia
- Thrombocytopenia
Monitoring Parameters
Baseline:- Blood pressure (supine, sitting, standing)
- Heart rate
- Liver function tests
- Complete blood count
- Prostate-specific antigen (for BPH patients)
- Renal function
- Blood pressure at each visit
- Orthostatic blood pressure changes
- BPH symptom score (IPSS)
- Urinary flow rates (for BPH)
- Adverse effects assessment
- Liver function (periodically)
Patient Education
- Take medication exactly as prescribed, usually at bedtime
- Do not crush or chew tablets
- Rise slowly from sitting or lying position to prevent dizziness
- Avoid driving or operating machinery until effects are known
- Report any dizziness, lightheadedness, or fainting
- Inform all healthcare providers about doxazosin use, especially before surgery
- Do not stop taking abruptly without medical supervision
- For BPH patients: Continue regular prostate cancer screenings
- Avoid alcohol as it may increase dizziness and orthostatic effects
- Report any prolonged or painful erections immediately
References
1. FDA Prescribing Information: Doxazosin Mesylate Tablets 2. Chobanian AV, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. JAMA 2003 3. Roehrborn CG, et al. The effects of doxazosin in men with benign prostatic hyperplasia. J Urol 2002 4. Elliott HL, Meredith PA. The pharmacodynamics of doxazosin in hypertensive patients. Br J Clin Pharmacol 1989 5. Kirby RS, et al. Efficacy and tolerability of doxazosin in benign prostatic hyperplasia. BMJ 1994 6. Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th Edition 7. Lexicomp Online, Hudson, Ohio: Wolters Kluwer Clinical Drug Information, Inc.