Uroxatral - Drug Monograph

Introduction

Uroxatral (alfuzosin hydrochloride) is an alpha-1 adrenergic receptor antagonist specifically indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH). Unlike other alpha-blockers, alfuzosin demonstrates uroselectivity, preferentially targeting alpha-1 receptors in the prostate and bladder neck while minimizing effects on vascular alpha-1 receptors. This monograph provides comprehensive clinical information about Uroxatral for healthcare professionals.

Mechanism of Action

Alfuzosin competitively and selectively blocks postsynaptic alpha-1 adrenergic receptors, primarily the alpha-1A subtype located in the prostate, bladder base, bladder neck, prostatic capsule, and prostatic urethra. By antagonizing these receptors, Uroxatral prevents norepinephrine-mediated contraction of smooth muscle in these areas, resulting in:

• Relaxation of prostate and bladder neck smooth muscle
• Reduction of bladder outlet obstruction
• Decreased urinary retention
• Improvement in urinary flow rates and BPH symptoms

The drug's uroselectivity results from its preferential binding to alpha-1A receptors over alpha-1B receptors (found in vascular smooth muscle), potentially reducing the incidence of cardiovascular side effects.

Indications

Uroxatral is FDA-approved for:

• Treatment of signs and symptoms of benign prostatic hyperplasia (BPH)

The drug is not indicated for:

• Treatment of hypertension
• Pediatric populations
• Female patients

Dosage and Administration

• Uroxatral 10 mg extended-release tablet once daily

• Take immediately after the same meal each day
• Swallow tablet whole; do not crush, chew, or split
• Consistent food intake enhances bioavailability and reduces peak plasma concentration fluctuations

• Renal impairment: No dosage adjustment needed for mild to moderate impairment. Use with caution in severe renal impairment (CrCl <30 mL/min)
• Hepatic impairment: Contraindicated in moderate to severe hepatic impairment (Child-Pugh B and C)
• Geriatric patients: No dosage adjustment required
• Race: No specific dosage recommendations based on race

Pharmacokinetics

• Bioavailability: ~49% under fed conditions
• Tmax: 8 hours post-dose
• Food effect: High-fat meal increases AUC by 50% and Cmax by 23%
• Steady-state: Achieved within 5 days

• Protein binding: 82-90%
• Volume of distribution: 3.2 L/kg
• Crosses blood-brain barrier minimally

• Primarily hepatic via CYP3A4
• Three main metabolites (inactive)
• No clinically significant active metabolites

• Half-life: 10 hours
• Clearance: 0.3 L/h/kg
• Excretion: Feces (69%), urine (24%)
• Dialysis: Not expected to enhance elimination

Contraindications

1. Moderate to severe hepatic impairment (Child-Pugh B and C) 2. Concomitant use with strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir) 3. History of hypersensitivity to alfuzosin or any component of the formulation 4. Severe renal impairment (CrCl <30 mL/min) due to limited clinical experience

Warnings and Precautions

• May cause syncope and orthostatic hypotension with or without symptoms
• Highest risk during initial dose and dose increases
• Caution in patients with symptomatic hypotension or concomitant antihypertensives

• Reported during cataract surgery in patients on alpha-blockers
• Inform ophthalmologists about alpha-blocker use
• Consider discontinuing before cataract surgery

• Rare reports of prolonged erection (>4 hours)
• Requires immediate medical attention to prevent permanent damage

• Rule out prostate cancer before initiating therapy
• Not a treatment for prostate cancer

• Use caution in patients with history of QT prolongation
• Monitor for angina in patients with coronary artery disease
• Not recommended for use with other alpha-blockers

Drug Interactions

• Strong CYP3A4 inhibitors: Ketoconazole, itraconazole, ritonavir - Contraindicated (increases alfuzosin AUC by 2.3-3.5 fold)
• Other alpha-blockers: Additive hypotensive effects - Avoid combination
• Phosphodiesterase-5 inhibitors: Additive hypotensive effects - Use with caution

• Moderate CYP3A4 inhibitors: Erythromycin, verapamil, diltiazem - Monitor for hypotension
• Antihypertensives: Calcium channel blockers, beta-blockers, ACE inhibitors - Monitor blood pressure
• Nitrates: Additive hypotensive effects

• Warfarin: No significant interaction observed in studies
• Digoxin, atenolol: No clinically significant interactions

Adverse Effects

• Dizziness (6.3%)
• Upper respiratory tract infection (3.0%)
• Headache (3.0%)
• Fatigue (2.6%)

• Orthostatic hypotension (0.6%)
• Syncope (0.1%)
• Palpitations (1.0%)
• Abdominal pain (1.5%)
• Constipation (1.4%)
• Erectile dysfunction (1.2%)
• Priapism (rare)

• Intraoperative Floppy Iris Syndrome
• Angina pectoris
• Tachycardia
• Hepatotoxicity
• Allergic reactions including rash, pruritus, urticaria

Monitoring Parameters

• Digital rectal examination (DRE) and prostate-specific antigen (PSA)
• Renal and hepatic function tests
• Blood pressure and heart rate (supine and standing)
• Assessment of BPH symptom score (IPSS)

• Blood pressure regularly, especially during initiation
• Orthostatic blood pressure measurements
• BPH symptom improvement assessment
• Adverse effect monitoring at each visit
• Hepatic function periodically

• Symptoms of hypotension (dizziness, lightheadedness)
• Any visual changes (especially before cataract surgery)
• Unusual or prolonged penile erections

Patient Education

• Take Uroxatral exactly as prescribed, after the same meal each day
• Do not crush, chew, or split tablets
• Rise slowly from sitting or lying position to prevent dizziness
• Avoid driving or operating machinery until effects are known
• Inform all healthcare providers about Uroxatral use, especially ophthalmologists
• Seek immediate medical attention for:

- Prolonged erection (>4 hours) - Severe dizziness or fainting - Chest pain or palpitations

• Maintain adequate fluid intake
• Avoid alcohol which may worsen dizziness
• Be cautious with hot showers or baths
• Report any new medications to your prescriber

• Keep all scheduled appointments
• Report any side effects promptly
• Do not stop medication without consulting your healthcare provider

References

1. FDA Prescribing Information: Uroxatral (alfuzosin hydrochloride) Extended-Release Tablets. 2010. 2. Roehrborn CG. Alfuzosin: overview of pharmacokinetics, safety, and efficacy of a clinically uroselective alpha-blocker. Urology. 2001;58(6 Suppl 1):55-63. 3. van Kerrebroeck P, Jardin A, Laval KU, et al. Efficacy and safety of a new prolonged release formulation of alfuzosin 10 mg once daily versus alfuzosin 2.5 mg thrice daily and placebo in patients with symptomatic benign prostatic hyperplasia. Eur Urol. 2000;37(3):306-313. 4. McVary KT, Roehrborn CG, Avins AL, et al. Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol. 2011;185(5):1793-1803. 5. Narayan P, Evans CP, Moon T. Long-term safety and efficacy of alfuzosin 10 mg once daily: a 2-year experience in 482 patients. BJU Int. 2003;92(7):795-800. 6. American Urological Association Guidelines on Management of Benign Prostatic Hyperplasia. 2021. 7. Lexicomp Online, Alfuzosin monograph. Accessed 2023. 8. Micromedex Solutions, Alfuzosin drug information. Truven Health Analytics. 2023.