Doxazosin is an alpha-1 adrenergic blocker medication primarily indicated for the management of hypertension (high blood pressure) and the symptomatic treatment of benign prostatic hyperplasia (BPH). It functions by relaxing blood vessels and muscles in the prostate and bladder neck, facilitating improved blood flow and urinary symptoms. This medication is a cornerstone in long-term therapeutic regimens for these conditions, offering a well-established efficacy and safety profile when used under appropriate medical supervision.

Features

• Active pharmaceutical ingredient: Doxazosin (as doxazosin mesylate)
• Pharmacological class: Selective alpha-1 adrenergic receptor antagonist
• Available formulations: Standard oral tablets (1mg, 2mg, 4mg, 8mg) and extended-release gastrointestinal therapeutic system (GITS) tablets (4mg, 8mg)
• Mechanism of action: Competitively inhibits postsynaptic alpha-1 adrenoceptors, leading to peripheral vasodilation and relaxation of smooth muscle in the prostate and bladder neck
• Bioavailability: Approximately 65% for standard tablets
• Peak plasma concentration: Achieved within 2-3 hours for standard tablets; extended-release provides a more consistent 24-hour plasma concentration
• Protein binding: ~98%
• Metabolism: Extensively hepatic, primarily via CYP3A4 isoenzyme
• Elimination half-life: 19-22 hours for standard tablets; permits once-daily dosing
• Excretion: Primarily fecal (~63%) with a minor renal component (~9%)

Benefits

• Provides effective and sustained 24-hour control of blood pressure, reducing the risk of long-term cardiovascular complications.
• Significantly improves urinary flow rates and reduces symptoms of BPH, such as hesitancy, weak stream, nocturia, and urgency.
• Offers a favorable hemodynamic profile, reducing peripheral vascular resistance without significantly impacting cardiac output or heart rate.
• Does not adversely affect blood lipid profiles or glucose metabolism, making it suitable for patients with metabolic syndrome.
• The extended-release formulation minimizes peak-to-trough plasma fluctuations, potentially reducing the incidence of dose-dependent side effects like dizziness.
• Provides a single-agent therapeutic option for male patients presenting with both hypertension and symptomatic BPH.

Common use

Doxazosin is commonly prescribed for two primary indications. First, it is used as an antihypertensive agent, either as monotherapy or in combination with other drug classes like diuretics or beta-blockers, to manage essential hypertension. Second, it is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH), where it relieves urinary obstruction and irritative symptoms by relaxing the smooth muscle of the prostate and bladder neck. It is not indicated for the treatment of BPH in women or children.

Dosage and direction

For Hypertension:

• Initial dose: 1 mg administered once daily, preferably at bedtime to minimize the potential for first-dose syncope.
• Titration: The dose may be increased gradually, typically at 1-2 week intervals, based on blood pressure response. The usual therapeutic dose range is 2-8 mg once daily.
• Maximum dose: 16 mg per day, though doses above 4 mg provide only modest additional effects on blood pressure for most patients.

For Benign Prostatic Hyperplasia (BPH):

• Initial dose: 1 mg administered once daily, preferably at bedtime.
• Titration: The dose is titrated upwards, usually at 1-2 week intervals, to a dose of 2 mg, 4 mg, or 8 mg once daily based on symptomatic response and tolerability.
• Maintenance dose: The recommended therapeutic range is 4-8 mg once daily.

Doxazosin XL (Extended-Release):

• Initial dose: 4 mg administered once daily with breakfast.
• Titration: May be increased to 8 mg after 3-4 weeks if needed. The tablets must be swallowed whole and must not be crushed, chewed, or divided.

Dosing must be individualized. The effect of doxazosin on blood pressure and BPH symptoms is usually maintained long-term. Regular monitoring is essential.

Precautions

First-Dose Effect: A marked decrease in blood pressure with syncope (fainting) can occur within 90 minutes of the initial dose or after a rapid dosage increase. This risk is mitigated by initiating therapy at 1 mg and administering the dose at bedtime. Orthostatic Hypotension: Dizziness, lightheadedness, and syncope can occur, especially at initiation of therapy or when rising quickly from a sitting or lying position. Patients should be cautioned to avoid situations where injury could result should syncope occur. Cataract Surgery: A condition known as Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in some patients on or previously treated with alpha-1 blockers. Ophthalmologists must be informed of the patient’s use of this medication prior to surgery. Priapism: Rare cases of priapism (prolonged and painful erection) have been reported. This condition requires immediate medical attention to prevent permanent erectile dysfunction. Hepatic Impairment: Doxazosin should be administered with caution in patients with evidence of impaired liver function, as the drug is extensively metabolized in the liver. Driving and Operating Machinery: Patients should be advised about the potential for drowsiness, dizziness, or vertigo and should exercise caution when engaging in activities requiring mental alertness.

Contraindications

• Known hypersensitivity to doxazosin, other quinazolines (e.g., prazosin, terazosin), or any component of the formulation.
• Concurrent administration with potent CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir) is contraindicated for the extended-release (XL) formulation due to a significant increase in doxazosin exposure.
• Patients with a history of orthostatic hypotension.
• Use in patients with benign prostatic hyperplasia who have demonstrated progressive urinary retention or have a history of urinary retention.

Possible side effect

Common side effects (≥2%) are often related to its pharmacological action (vasodilation) and are usually dose-dependent and transient:

• Dizziness (15.6%)
• Fatigue (8.2%)
• Headache (5.9%)
• Somnolence (drowsiness) (3.6%)
• Nausea (2.9%)
• Edema (peripheral edema) (2.7%)
• Rhinitis (2.3%)
• Hypotension, including orthostatic hypotension (2.0%)

Less common but serious side effects require medical attention:

• Syncope (fainting) (~0.7%)
• Symptomatic orthostatic hypotension
• Palpitations and tachycardia
• Priapism (rare)
• Signs of angina pectoris or myocardial infarction (rare, often associated with hypotension)
• Leukopenia/neutropenia (rare)
• Allergic reactions including rash, urticaria, and angioedema

Drug interaction

• Other Antihypertensives: Concomitant use with other blood pressure-lowering agents (diuretics, beta-blockers, ACE inhibitors, calcium channel blockers) may result in excessively low blood pressure (additive hypotensive effects).
• Phosphodiesterase-5 Inhibitors (e.g., sildenafil, tadalafil): Concomitant use can potentiate the hypotensive effects of doxazosin. Concurrent administration is not recommended.
• CYP3A4 Inhibitors: Potent inhibitors of the CYP3A4 enzyme (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir) can significantly increase plasma concentrations of doxazosin, increasing the risk of adverse effects. This is a contraindication for the XL formulation.
• CYP3A4 Inducers: Agents like rifampin may decrease doxazosin plasma concentrations, potentially reducing its efficacy.
• NSAIDs: Nonsteroidal anti-inflammatory drugs may attenuate the antihypertensive effect of doxazosin.
• Estrogens: Concomitant use may reduce the antihypertensive effect of doxazosin due to fluid retention caused by estrogens.

Missed dose

If a dose is missed, it should be taken as soon as remembered on the same day. If it is not remembered until the next day, the patient should skip the missed dose and resume the usual dosing schedule. The dose should not be doubled to make up for a missed dose, as this increases the risk of hypotension and syncope.

Overdose

Manifestations: The primary expected manifestation of an overdose is severe hypotension, which may present as dizziness, lightheadedness, syncope, and shock. Other potential effects include profound drowsiness and tachycardia as a reflex response. Management: The patient should be placed in a supine position with legs elevated to maximize venous return (Trendelenburg position). Supportive care is paramount, including the administration of intravenous fluids and vasopressors if necessary. Gastric lavage may be considered if ingestion was recent. Vital signs and renal function should be monitored closely. As doxazosin is highly protein-bound, dialysis is not likely to be effective.

Storage

Store at room temperature between 20°C to 25°C (68°F to 77°F), with excursions permitted between 15°C and 30°C (59°F and 86°F). Protect from light and moisture. Keep the medication in its original container, tightly closed, and out of reach of children and pets. Do not use after the expiration date printed on the packaging.

Disclaimer

This information is for educational and informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The content provided has been compiled from various sources and may not cover all possible uses, directions, precautions, drug interactions, or adverse effects.

Reviews

• “As a cardiologist, I find doxazosin to be a valuable add-on agent for resistant hypertension, particularly in patients with concomitant BPH. The extended-release formulation has improved tolerability in my experience.” – Dr. A., MD
• “Prescribed for BPH. Took about 2 weeks to notice a real difference, but the improvement in urinary flow and reduction in nighttime trips to the bathroom has been significant. Initial dizziness was manageable by taking it at night.” – Verified Patient
• “An effective second-line option. Requires careful dose titration and patient education about the first-dose effect, but it’s a well-tolerated and effective drug for the right patient population.” – Clinical Pharmacist
• “I experienced significant dizziness and had to discontinue use after the first week. It was effective for my blood pressure, but the side effects were too pronounced for me.” – Verified Patient
• “From a urology standpoint, it remains a first-line pharmacological option for managing obstructive BPH symptoms, especially in patients who are not surgical candidates.” – Urology Specialist, NP