Doxazosin

• Benign Prostatic Hyperplasia (BPH)
• Hypertension
• Lower Urinary Tract Symptoms
• Prostate Enlargement

Doxazosin is an alpha-1 adrenergic receptor blocker used for the treatment of benign prostatic hyperplasia (BPH) and hypertension. This long-acting alpha-blocker provides effective relief of urinary symptoms associated with BPH while also offering blood pressure-lowering effects.

Mechanism of Action

Doxazosin selectively blocks alpha-1 adrenergic receptors in the prostate gland, prostatic capsule, prostatic urethra, bladder neck, and vascular smooth muscle. In BPH, blockade of alpha-1 receptors in the prostate and bladder neck relaxes smooth muscle, reducing urethral resistance and improving urine flow. For hypertension, alpha-1 blockade in arterial and venous smooth muscle causes vasodilation, reducing peripheral vascular resistance and blood pressure. Doxazosin has selectivity for alpha-1 receptors over alpha-2 receptors, minimizing the reflex tachycardia seen with non-selective alpha-blockers. The medication has a long half-life, allowing once-daily dosing.

Available Formulations

Doxazosin mesylate is available as immediate-release tablets (1 mg, 2 mg, 4 mg, 8 mg) and extended-release tablets (4 mg, 8 mg). The immediate-release tablets can be taken with or without food. The extended-release tablets (for BPH only) should be swallowed whole with breakfast and should not be crushed, chewed, or divided.

Medical Uses

Doxazosin is FDA-approved for the treatment of signs and symptoms of benign prostatic hyperplasia (both formulations) and for the management of hypertension (immediate-release only). For BPH, it improves urinary flow rate and reduces symptoms such as hesitancy, frequency, nocturia, and incomplete emptying. The ALLHAT trial raised concerns about using alpha-blockers as first-line hypertension therapy, so it is typically used as add-on therapy. Off-label uses include ureteral stone expulsion.

Dosing Guidelines

For BPH with immediate-release tablets, start with 1 mg once daily, titrating to 2 mg, 4 mg, then 8 mg at 1-2 week intervals based on response (maximum 8 mg daily). For the extended-release formulation, start with 4 mg once daily with breakfast, increasing to 8 mg after 3-4 weeks if needed. For hypertension, start with 1 mg once daily, increasing gradually to a maximum of 16 mg daily in divided doses. First-dose hypotension can occur; initial dose should be taken at bedtime.

Important Safety Information

Doxazosin can cause marked hypotension, especially with the first dose or after dose increases; patients should be warned about syncope risk. Priapism has rarely occurred; patients should seek immediate medical attention if painful erection lasts more than 4 hours. Intraoperative floppy iris syndrome (IFIS) has been observed during cataract surgery in patients taking alpha-blockers; patients should inform their ophthalmologist before surgery. The medication should be used with caution in patients with pre-existing hypotension or those taking other antihypertensives.

Drug Interactions

Concurrent use with phosphodiesterase-5 (PDE-5) inhibitors (sildenafil, tadalafil, vardenafil) may cause additive hypotensive effects; use with caution. Other antihypertensive medications may enhance hypotensive effects. Strong CYP3A4 inhibitors may increase doxazosin levels. Doxazosin may reduce the antihypertensive effect of clonidine withdrawal. No significant interaction with digoxin, warfarin, or NSAIDs has been observed.

Special Populations

There are no adequate studies in pregnant women; use during pregnancy only if clearly needed. Doxazosin accumulates in breast milk; breastfeeding is not recommended. Safety and efficacy have not been established in pediatric patients. Elderly patients may be more susceptible to hypotensive effects; start with lower doses. No dose adjustment is required for renal impairment. The medication is extensively metabolized in the liver; use with caution in hepatic impairment.