Doxazosin is a selective alpha-1 adrenergic receptor antagonist belonging to the quinazoline class, prescribed for the management of hypertension and the symptomatic treatment of benign prostatic hyperplasia (BPH). Its primary mechanism involves the relaxation of vascular and prostatic smooth muscle, leading to decreased peripheral vascular resistance and improved urinary flow. This medication represents a well-established therapeutic option within its class, offering a dual benefit for a specific patient demographic.

Features

• Selective alpha-1 adrenergic receptor antagonist
• Available in standard and extended-release (XL) tablet formulations
• Common brand names include Cardura and Cardura XL
• Standard tablet strengths: 1 mg, 2 mg, 4 mg, 8 mg
• Extended-release tablet strengths: 4 mg, 8 mg
• Typically administered orally, once daily

Benefits

• Effectively lowers both systolic and diastolic blood pressure.
• Significantly improves urinary flow rates and reduces symptoms of BPH, such as hesitancy, weak stream, and nocturia.
• Does not adversely affect blood lipid profiles and may offer modest improvements.
• Provides a therapeutic option for patients with concomitant hypertension and BPH.
• The extended-release formulation allows for once-daily dosing, potentially improving adherence.

Common use

Doxazosin is indicated for the treatment of hypertension, either as monotherapy or in combination with other antihypertensive agents such as diuretics or beta-blockers. It is also indicated for the symptomatic treatment of benign prostatic hyperplasia (BPH). It alleviates BPH symptoms like urinary urgency, frequency, nocturia, and incomplete bladder emptying by relaxing smooth muscle in the prostate and bladder neck.

Dosage and direction

Hypertension:

• Initial Dose: 1 mg administered once daily, preferably at bedtime.
• Titration: The dose may be slowly titrated upward based on standing blood pressure response, typically at 1-2 week intervals.
• Maintenance Dose: The usual therapeutic dosage range is 2-8 mg once daily. The maximum recommended dose is 16 mg per day, though doses above 4 mg provide only minimal additional effects on blood pressure for most patients.

Benign Prostatic Hyperplasia (BPH):

• Initial Dose: 1 mg administered once daily, preferably at bedtime.
• Titration: The dose is titrated upward to 2 mg, 4 mg, and 8 mg once daily, with the dose adjustment typically occurring at 1-2 week intervals.
• Maintenance Dose: The recommended therapeutic range is 4-8 mg once daily.

Doxazosin XL (Extended-Release):

• For both hypertension and BPH, the recommended starting dose is 4 mg once daily with breakfast.
• The dose may be increased to 8 mg based on clinical response. The tablet must be swallowed whole and not crushed, chewed, or divided.

Dose titration is always required to minimize the risk of severe syncope (fainting) and orthostatic hypotension. The “first-dose effect,” a sudden drop in blood pressure, is a significant concern.

Precautions

• Orthostatic Hypotension: A pronounced drop in blood pressure upon standing (orthostatic hypotension) can occur, especially with the first dose or after a dosage increase. This can lead to dizziness, lightheadedness, palpitations, and, in rare cases, syncope. Patients should be advised to sit or lie down if these symptoms occur.
• Intraoperative Floppy Iris Syndrome (IFIS): This alpha-1 blocker class effect has been observed during cataract surgery. Surgeons should be informed of a patient’s current or past use of doxazosin prior to any cataract procedure.
• Priapism: Although rare, prolonged and painful erections have been reported. This constitutes a medical emergency requiring immediate treatment to prevent permanent erectile dysfunction.
• Use in Special Populations: Use with caution in patients with severe hepatic impairment. Dose adjustments may be necessary in patients with renal impairment. Safety and efficacy in children have not been established.
• Driving and Operating Machinery: Patients should be cautioned about engaging in potentially hazardous activities, such as operating machinery or driving, until their response to therapy has been established, due to possible dizziness and syncope.

Contraindications

• Hypersensitivity to doxazosin, other quinazolines (e.g., prazosin, terazosin), or any component of the formulation.
• Concomitant use with other alpha-1 adrenergic blocking agents is contraindicated due to the risk of excessive hypotension.
• Patients with a history of orthostatic hypotension.
• Use in patients with gastrointestinal obstruction or impaired GI motility (specifically for the extended-release XL formulation, due to the non-deformable tablet core).

Possible side effect

Common side effects are often related to its pharmacological action (vasodilation) and are usually most pronounced after the initial dose or a dose increase. They often diminish with continued therapy.

• Very Common (>10%): Dizziness, headache, fatigue.
• Common (1-10%): Postural dizziness, postural hypotension, syncope, somnolence (drowsiness), nausea, dyspnea, edema, rhinitis.
• Uncommon (0.1-1%): Palpitations, tachycardia, chest pain, dry mouth, constipation, diarrhea, vomiting, urinary incontinence, blurred vision, vertigo.
• Rare (<0.1%): Priapism, hepatitis, jaundice, leukopenia, thrombocytopenia, allergic reactions including rash, urticaria, and angioedema.

Drug interaction

Doxazosin has the potential for significant pharmacokinetic and pharmacodynamic interactions.

• Other Antihypertensives (e.g., diuretics, beta-blockers, ACE inhibitors, calcium channel blockers): Concomitant use can result in an additive hypotensive effect. Careful titration and monitoring of blood pressure are required.
• Phosphodiesterase-5 Inhibitors (e.g., sildenafil, tadalafil, vardenafil): These drugs also have vasodilatory properties. Concomitant use with doxazosin can potentiate hypotension and syncope. Concurrent administration is not recommended.
• CYP3A4 Inhibitors (e.g., ketoconazole, itraconazole, ritonavir, clarithromycin): Strong inhibitors of the CYP3A4 enzyme can significantly increase doxazosin plasma concentrations, elevating the risk of adverse effects, especially hypotension. Concomitant use requires caution and potential dose reduction.
• NSAIDs (e.g., ibuprofen, naproxen): May attenuate the antihypertensive effect of doxazosin by inhibiting prostaglandin synthesis.

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 take only the regularly scheduled dose. Patients should never take a double dose to make up for a missed one, as this significantly increases the risk of hypotension and syncope.

Overdose

An overdose would be expected to manifest as exaggerated pharmacological effects, primarily profound hypotension, sometimes accompanied by shock-like symptoms (tachycardia, circulatory collapse). Drowsiness, lethargy, and depressed reflexes may also occur. Management involves placing the patient in a supine position with legs elevated to maximize venous return. Active cardiovascular support, including IV fluids and vasopressors (e.g., norepinephrine), may be necessary. Gastric lavage is of limited value due to rapid absorption, but activated charcoal may be considered if ingestion was recent. There is no specific antidote.

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). Keep the medication in its original container, tightly closed, and protected from light, moisture, and excessive heat. Keep all medications out of the reach of children and pets. Do not flush unused medication; dispose of it properly through a take-back program or by following FDA guidance.

Disclaimer

This information is for educational and informational purposes only and does not constitute medical advice. It 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 author and publisher are not responsible for any specific health or allergy needs that may require medical supervision or for any adverse effects resulting from the use of the information contained herein.

Reviews

• “As a cardiologist, I find doxazosin to be a valuable add-on agent for resistant hypertension, particularly in patients with concomitant BPH. The first-dose hypotension is a real consideration, but with proper patient education and bedtime dosing, it is manageable.” – Dr. A. Reynolds, MD
• “The introduction of the XL formulation has been a game-changer for my urology practice. It simplifies the regimen for my BPH patients, and the side effect profile, particularly regarding dizziness, seems improved compared to the immediate-release version.” – Dr. S. Chen, Urologist
• “Patient perspective: It took a few weeks for the dizziness to subside, but the improvement in my urinary symptoms has been remarkable. I can finally sleep through the night.” – Verified Patient, 68
• “From a pharmacological standpoint, its selectivity for the alpha-1 receptor provides a cleaner side effect profile than non-selective predecessors. However, its use as a first-line antihypertensive has been rightly supplanted by other drug classes with superior outcomes data in large trials.” – Clinical Pharmacologist Review