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Sunday, July 27, 2025

Doxazosin


Doxazosin is a long-acting selective alpha-1 adrenergic receptor antagonist (alpha-blocker) used primarily to treat hypertension and benign prostatic hyperplasia (BPH) in men. It works by relaxing vascular smooth muscle and the smooth muscle in the bladder neck and prostate, thereby reducing blood pressure and improving urinary flow in men with lower urinary tract symptoms (LUTS) associated with BPH. Doxazosin is considered advantageous due to its once-daily dosing, sustained efficacy, and dual therapeutic roles in both cardiovascular and urological medicine.

This detailed profile presents the drug’s mechanism of action, pharmacokinetics, therapeutic uses, dosing, contraindications, precautions, side effects, and drug interactions.

Pharmacological Classification

  • Therapeutic class: Antihypertensive; Urologic agent

  • Pharmacologic class: Selective alpha-1 adrenergic blocker

  • ATC code: C02CA04 (for hypertension), G04CA01 (for BPH)

  • Legal status: Prescription-only (Rx)

Brand Names and Formulations

  • Brand names: Cardura®, Doxadura®, Raporsin®, Doxalong®, Carduran®

  • Available forms:

    • Immediate-release (IR) tablets: 1 mg, 2 mg, 4 mg

    • Modified-release (MR) tablets: 4 mg, 8 mg

Mechanism of Action

Doxazosin selectively antagonizes postsynaptic alpha-1 adrenergic receptors located in:

  1. Vascular smooth muscle → leading to vasodilation, decreased peripheral resistance, and lowered blood pressure

  2. Smooth muscle in the bladder neck and prostate → leading to reduced dynamic outflow obstruction in BPH

It does not block alpha-2 receptors, which minimizes reflex tachycardia. Doxazosin’s long half-life (~22 hours) allows for once-daily dosing and smooth 24-hour blood pressure control.

Indications

Approved Uses

  • Essential hypertension (alone or in combination)

  • Benign prostatic hyperplasia (BPH) with LUTS (lower urinary tract symptoms)

  • Coexisting hypertension and BPH

Off-label Uses

  • Ureteric stone expulsion therapy (alpha-blockers help relax ureteral smooth muscle)

  • Raynaud’s phenomenon

  • Nightmares in PTSD (less common than prazosin)

Dosage and Administration

Hypertension (Immediate-release)

  • Initial dose: 1 mg once daily (to minimize risk of postural hypotension)

  • Maintenance dose: 2–4 mg once daily

  • Maximum dose: 16 mg/day

  • Titrate slowly based on blood pressure response

BPH (Immediate-release)

  • Initial dose: 1 mg once daily at bedtime

  • Titration: Increase to 2 mg, then 4 mg at 1–2 week intervals if needed

  • Maximum dose: 8 mg once daily

Modified-release tablets (for BPH)

  • Starting dose: 4 mg once daily

  • May increase to 8 mg daily after 1–2 weeks if necessary

  • Take with or without food, preferably at the same time each day

Pharmacokinetics

  • Absorption: ~65% bioavailability

  • Time to peak plasma concentration:

    • IR: 2–3 hours

    • MR: 6–8 hours

  • Protein binding: ~98%

  • Metabolism: Hepatic (CYP3A4 substrate)

  • Half-life: ~22 hours

  • Excretion: Primarily in feces (63%), urine (~5–10%)

Contraindications

  • History of orthostatic hypotension

  • Hypersensitivity to doxazosin or other quinazolines

  • Monotherapy in patients with overflow incontinence or anuria without demonstrable bladder contractility

  • Severe hepatic impairment (metabolism may be impaired)

Warnings and Precautions

First-dose phenomenon

  • Marked postural hypotension, dizziness, and even syncope may occur after the first dose or dose escalation

  • To prevent: start with 1 mg at bedtime, especially in elderly or volume-depleted patients

Intraoperative Floppy Iris Syndrome (IFIS)

  • Reported during cataract surgery in patients taking or previously treated with alpha-blockers like doxazosin

  • Inform ophthalmologist before surgery

Liver Impairment

  • Use cautiously; primarily metabolized by the liver

  • Avoid in severe hepatic dysfunction

Heart Failure

  • Doxazosin may cause fluid retention

  • Caution in patients with congestive heart failure not controlled with diuretics

Prostate Cancer

  • Rule out prostate cancer before initiating treatment for BPH as symptoms may overlap

Adverse Effects

Common (≥1%)

  • Dizziness, fatigue, headache

  • Postural hypotension, palpitations, edema

  • Nasal congestion

  • Dry mouth

  • Somnolence

  • Gastrointestinal discomfort, nausea

Uncommon

  • Syncope

  • Chest pain, dyspnea

  • Visual disturbances

  • Urinary incontinence

  • Ejaculatory dysfunction

Rare but Serious

  • Angioedema

  • Priapism (requires emergency treatment)

  • Liver enzyme elevations, hepatitis

  • Leukopenia or thrombocytopenia (rare hematologic reactions)

Drug Interactions

  • Antihypertensives: Additive effect; monitor BP closely

  • Phosphodiesterase-5 inhibitors (e.g. sildenafil, tadalafil): Risk of marked hypotension; stagger administration by several hours

  • CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin): May increase doxazosin levels

  • NSAIDs: May attenuate antihypertensive effect

  • Diuretics or beta-blockers: Additive hypotensive effect

  • Alcohol: Enhances orthostatic hypotension

Use in Special Populations

Elderly

  • Increased sensitivity to hypotensive effects

  • Start at lowest dose (1 mg)

Pregnancy

  • Category C (not well-studied)

  • Use only if clearly needed

Lactation

  • Excreted in animal milk; not recommended in breastfeeding women

Renal Impairment

  • No dosage adjustment needed; not renally eliminated

Hepatic Impairment

  • Use caution; avoid in severe liver disease

Clinical Trials and Guideline Recommendations

  • ALLHAT Study: Showed higher risk of heart failure with doxazosin compared to diuretics as initial therapy for hypertension

  • Still used as adjunctive therapy in resistant hypertension, especially in patients with BPH

  • NICE guidelines (UK) recommend doxazosin as:

    • An option for hypertension if other agents not tolerated

    • First-line for BPH when LUTS are present

  • AUA Guidelines: Alpha-blockers, including doxazosin, are first-line therapy for BPH with LUTS

Comparison with Similar Drugs (without table)

Doxazosin vs. Tamsulosin

  • Doxazosin is non-selective (blocks all alpha-1 receptors), while tamsulosin is selective for alpha-1A (mainly in prostate)

  • Doxazosin is also approved for hypertension; tamsulosin is not

  • Tamsulosin has fewer cardiovascular side effects, but more ejaculatory dysfunction

  • Doxazosin requires dose titration; tamsulosin does not

Doxazosin vs. Terazosin

  • Similar spectrum and use

  • Doxazosin has a longer half-life (22 hours vs. 12 hours)

  • Doxazosin generally requires once-daily dosing

Doxazosin vs. Prazosin

  • Prazosin has a much shorter half-life and requires multiple daily doses

  • Doxazosin is preferred for chronic use, while prazosin is more often used in PTSD-related nightmares (off-label)

Patient Counseling Points

  • Take first dose at bedtime to reduce dizziness

  • Avoid driving or operating machinery after the first few doses

  • Rise slowly from sitting or lying to prevent orthostatic hypotension

  • Report any fainting, swelling, or palpitations

  • Inform ophthalmologist before cataract surgery

  • Do not stop the medication abruptly without medical advice

  • Maintain regular blood pressure checks

  • For BPH, note improvement may take 1–2 weeks




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