Doxazosin

Doxazosin is an alpha-1 adrenergic receptor antagonist, a medication belonging to the class of drugs known as alpha-blockers. It is primarily prescribed for the management of hypertension (high blood pressure) and the treatment of urinary symptoms associated with benign prostatic hyperplasia (BPH). By selectively blocking alpha-1 receptors located on vascular smooth muscle and in the prostate and bladder neck, doxazosin induces vasodilation and relaxation of smooth muscle in the urinary tract. This dual mechanism of action makes it a versatile therapeutic agent for cardiovascular and urological conditions, offering a well-established profile backed by extensive clinical use and research.

Features

• Active pharmaceutical ingredient: Doxazosin mesylate
• Drug class: Selective alpha-1 adrenergic receptor antagonist
• Available formulations: Oral tablets (standard and extended-release)
• Standard tablet strengths: 1 mg, 2 mg, 4 mg, 8 mg
• Extended-release (XL) tablet strengths: 4 mg, 8 mg
• Mechanism of Action: Competitively blocks postsynaptic alpha-1 adrenoceptors
• Bioavailability: Approximately 65%
• Protein binding: 98%
• Metabolism: Extensive hepatic metabolism primarily via CYP3A4 isoenzyme
• Elimination half-life: 22 hours (standard); 15-19 hours (extended-release)
• Excretion: Primarily fecal (~63%) with minor renal elimination (~9%)

Benefits

• Provides effective reduction of both systolic and diastolic blood pressure through peripheral vasodilation.
• Significantly improves urinary flow rates and reduces symptoms of BPH, such as hesitancy, weak stream, and nocturia.
• Offers a favorable metabolic profile, as it does not adversely affect blood glucose or lipid levels, making it suitable for diabetic patients.
• The extended-release formulation allows for convenient once-daily dosing, improving patient adherence.
• Can be used as monotherapy or in combination with other antihypertensive agents (e.g., diuretics, beta-blockers, ACE inhibitors) for synergistic effects.
• Provides rapid onset of action for symptomatic relief in BPH, with improvements often noted within 1-2 weeks.

Common use

Doxazosin is indicated for the treatment of hypertension, either as monotherapy or in combination with other antihypertensive drugs. It is also indicated for the symptomatic treatment of benign prostatic hyperplasia (BPH). In BPH, it is effective in treating both obstructive symptoms (impaired urinary flow, straining) and irritative symptoms (urgency, frequency, nocturia). Its use is supported by major clinical guidelines from organizations such as the American Heart Association (AHA) and the European Association of Urology (EAU). While not a first-line agent for hypertension per most guidelines, it remains a valuable option, especially in patients with concomitant BPH.

Dosage and direction

For Hypertension (using standard tablets):

• Initial Dose: 1 mg administered once daily, preferably at bedtime to minimize the risk of first-dose hypotension.
• Titration: The dose may be increased gradually, typically at 1-2 week intervals, based on blood pressure response and tolerability.
• Maintenance Dose: The usual therapeutic dose range is 2-8 mg once daily. The maximum recommended dose is 16 mg per day, though doses above 4 mg daily provide only modest additional effects on blood pressure.

For Benign Prostatic Hyperplasia (BPH - using standard tablets):

• Initial Dose: 1 mg administered once daily, preferably at bedtime.
• Titration: The dose is titrated upward, usually at 1-2 week intervals, to a dose of 2 mg, 4 mg, or 8 mg once daily, as needed to achieve symptom improvement.
• Maintenance Dose: The recommended therapeutic range is 4-8 mg once daily.

For Doxazosin XL (Extended-Release) Tablets:

• The recommended initial dose for both hypertension and BPH is 4 mg once daily with breakfast.
• The dose may be increased to 8 mg based on clinical response. If therapy is discontinued for several days, therapy should be restarted using the 4 mg once-daily dose.
• The tablets must be swallowed whole and must not be crushed, chewed, or divided.

Dosage adjustment is recommended in patients with impaired hepatic function. The drug may be taken with or without food.

Precautions

First-Dose Effect: A marked decrease in blood pressure, with syncope (fainting) and postural dizziness, can occur within 30 to 90 minutes after the initial dose or any subsequent rapid dose increase. This risk is minimized by initiating therapy at the 1 mg dose and administering it at bedtime. Orthostatic Hypotension: Patients should be cautioned about the potential for dizziness, lightheadedness, or fainting, particularly when rising from a sitting or lying position. This is more common at the initiation of therapy. Priapism: Although rare, prolonged and painful erections have been reported with alpha-blocker use. This condition requires immediate medical attention to prevent permanent erectile dysfunction. Cataract Surgery: The Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in patients treated with alpha-1 blockers. Surgeons should be informed in advance of a patient’s use of doxazosin. Hepatic Impairment: Doxazosin should be administered with caution in patients with evidence of impaired hepatic function or to patients receiving drugs known to influence hepatic metabolism. Driving and Operating Machinery: Patients should be advised of the potential for drowsiness or somnolence and to avoid driving or operating hazardous machinery until their response to the drug has been determined.

Contraindications

• Hypersensitivity to doxazosin, any other quinazolines (e.g., prazosin, terazosin), or any component of the formulation.
• Patients with a history of orthostatic hypotension.
• Concurrent use with other alpha-adrenergic blocking agents (e.g., tamsulosin, alfuzosin) due to the potential for additive effects and severe hypotension.
• Patients with severe hepatic impairment.
• Use in patients with gastrointestinal obstruction or impaired motility (specifically for the extended-release formulation, due to the risk of tablet retention).

Possible side effect

Doxazosin is generally well-tolerated, but side effects are dose-dependent and often related to its pharmacological action. The most common side effects include:

• Very Common (≥1/10): Dizziness, headache, fatigue.
• Common (≥1/100 to <1/10): Postural dizziness, postural hypotension, somnolence (drowsiness), nausea, dyspnea (shortness of breath), edema (swelling), rhinitis.
• Uncommon (≥1/1,000 to <1/100): Palpitations, tachycardia, chest pain, abdominal pain, diarrhea, vomiting, dry mouth, nervousness, rash, pruritus (itching), urinary incontinence, blurred vision, pain.
• Rare (≥1/10,000 to <1/1,000): Syncope (fainting), priapism, hepatitis, jaundice, leukopenia, thrombocytopenia.
• Frequency not known: Intraoperative Floppy Iris Syndrome (IFIS).

Drug interaction

Doxazosin is subject to several clinically significant drug interactions, primarily due to its additive hypotensive effects and metabolism via CYP3A4.

• Other Antihypertensives (Diuretics, Beta-Blockers, ACE Inhibitors, Calcium Channel Blockers): Concomitant use can result in additive hypotensive effects. Careful titration and blood pressure monitoring are required.
• Phosphodiesterase-5 Inhibitors (e.g., Sildenafil, Tadalafil): Concomitant use can potentiate the hypotensive effect of doxazosin. Concomitant use is not recommended.
• Strong CYP3A4 Inhibitors (e.g., Ketoconazole, Itraconazole, Ritonavir, Clarithromycin): These drugs can significantly increase doxazosin plasma concentrations, enhancing its effects and the risk of hypotension. Concomitant use should be avoided or the doxazosin dose should be reduced with close monitoring.
• Other Alpha-Adrenergic Blocking Agents: Concomitant use is contraindicated due to the high risk of severe hypotension and syncope.
• Medications that Lower Blood Pressure (e.g., Nitrates): Additive hypotensive effects may occur.
• Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): May attenuate the hypotensive effect of doxazosin.

Missed dose

If a dose is missed, it should be taken as soon as remembered on the same day. If it is almost time for the next scheduled dose, the missed dose should be skipped. The patient should not take a double dose to make up for the missed one. This is particularly important due to the risk of hypotension with an increased dose.

Overdose

An overdose would be expected to manifest as exaggerated pharmacological effects, primarily severe hypotension, sometimes accompanied by shock-like states and profound dizziness, drowsiness, or syncope. The patient should be placed in a supine position immediately, with the head lowered and legs elevated. Supportive care is the mainstay of treatment, including intravenous fluids and vasopressor agents (e.g., norepinephrine) if necessary. Gastric lavage may be considered if ingestion was recent. Vital signs and renal function should be monitored closely. Doxazosin is not dialyzable due to its high protein binding.

Storage

• Store at room temperature between 20°C to 25°C (68°F to 77°F).
• Protect from light and moisture.
• Keep in the original container or blister pack to protect from light.
• Keep 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 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 does not recommend or endorse any specific tests, physicians, products, procedures, opinions, or other information that may be mentioned.

Reviews

• “As a cardiologist with over 20 years of experience, doxazosin remains a valuable tool in my armamentarium, particularly for hypertensive patients with concomitant BPH. Its predictable hemodynamic effects and once-daily dosing support long-term adherence.” – Dr. A. Sharma, MD
• “In my urology practice, the symptomatic improvement doxazosin provides for my BPH patients is often rapid and significant. The first-dose effect is a manageable consideration with proper patient education and dosing.” – Dr. R. Evans, Urologist
• “Clinical trial data consistently demonstrates doxazosin’s efficacy in reducing both sitting and standing blood pressure. Its role in the ALLHAT trial, while informing its place in therapy, should not overshadow its utility in appropriately selected patients.” – Clinical Pharmacologist Review
• “The extended-release formulation has been a game-changer for many of my older patients on polypharmacy, simplifying their regimen and reducing the pill burden without compromising efficacy for their BPH symptoms.” – Geriatric Medicine Specialist