Alfuzosin Hydrochloride

Pronunciation: (al-FUE-zoe-sin HYE-droe-KLOR-ide)
Class: Antiadrenergic agent, peripherally acting

Trade Names

Uroxatral
- Tablets, ER 10 mg

Xatral (Canada)

Pharmacology

Selective blockade for alpha-1-adrenergic receptors in the lower urinary tract, which causes smooth muscle in the bladder neck and prostate to relax, resulting in improved urine flow and a reduction in symptoms of benign prostatic hyperplasia (BPH).

Pharmacokinetics

Absorption

Bioavailability is about 49%. T _max is 8 h. The C _max and AUC are about 13.6 ng/mL and 194 ng•h/mL, respectively. Steady-state is reached with the second dose. The extent of absorption is 50% lower under fasting conditions; should be taken immediately following a meal.

Distribution

Following IV administration, the Vd is about 3.2 L/kg. Protein binding is 82% to 90%.

Metabolism

Extensive hepatic metabolism with only 11% excreted unchanged in the urine. The major isozyme responsible for metabolism is CYP3A4.

Elimination

After 7 days, 69% is recovered in the feces and 24% in the urine. Elimination half-life is 10 h (oral).

Special Populations

Renal Function Impairment

The mean C _max and AUC values were increased about 50% in patients with mild, moderate, or severe renal impairment.

Hepatic Function Impairment

In patients with moderate or severe hepatic function impairment, plasma concentrations of alfuzosin were increased 3- to 4-fold.

Elderly

The concentrations in patients 75 years of age and older were approximately 35% greater than in those younger than 65 years of age.

Indications and Usage

Treatment of signs and symptoms of BPH.

Contraindications

Patients with moderate or severe hepatic impairment; coadministration with potent CYP3A4 inhibitors (eg, itraconazole, ketoconazole, ritonavir); hypersensitivity to any component of the product.

Dosage and Administration

Adults

PO 10 mg/day.

General Advice

• Should be taken immediately after the same meal each day.
• Do not cut, chew, or crush tablet; swallow tablet whole.

Storage/Stability

Store at 59° to 86°F. Protect from light and moisture.

Drug Interactions

Alpha-blockers (eg, prazosin)

Other alpha-blockers should not be coadministered.

Amiodarone

Alfuzosin concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions, including hypotension. Use with caution and monitor the patient's response.

Antihypertensive medications, nitrates

Risk of hypotension and syncope may be increased. Use with caution.

Beta-adrenergic blockers (eg, atenolol, propranolol)

Severity and duration of hypotension following the first dose of alfuzosin may be increased in patients receiving beta-adrenergic blockers. In addition, plasma levels of alfuzosin and atenolol may be elevated, increasing the pharmacologic effects and risk of adverse reactions, including hypotension. Use with caution.

Cimetidine

Alfuzosin levels may be elevated, increasing the pharmacologic and adverse reactions.

Clarithromycin, nefazodone

Alfuzosin concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions, including hypotension. If possible, avoid coadministration with alfuzosin.

Food

Alfuzosin absorption may be decreased under fasting conditions. Alfuzosin should be taken immediately after a meal.

Moderate CYP3A4 inhibitors (eg, diltiazem)

Alfuzosin plasma levels may be elevated, increasing the pharmacologic effects and risk of adverse reactions, including hypotension. Use with caution.

Phosphodiesterase type 5 inhibitors (eg, sildenafil, tadalafil, vardenafil)

The risk of hypotension may be increased. Doses of sildenafil greater then 25 mg should be avoided within 4 h of alfuzosin administration. Use with caution.

Potent CYP3A4 inhibitors (eg, itraconazole, ketoconazole, ritonavir)

Because plasma concentrations of alfuzosin may be increased more than 2-fold, coadministration of these agents is contraindicated.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Orthostatic hypotension (7%); angina pectoris in patients with preexisting coronary artery disease, tachycardia (postmarketing).

CNS

Dizziness (6%); fatigue, headache (3%).

Dermatologic

Pruritus, rash, urticaria (postmarketing).

EENT

Pharyngitis, sinusitis (1% to 2%); flushing, rhinitis (postmarketing).

GI

Abdominal pain, constipation, dyspepsia, nausea (1% to 2%); diarrhea (postmarketing).

Genitourinary

Impotence (1% to 2%); priapism (postmarketing).

Respiratory

Upper respiratory tract infection (3%); bronchitis (1% to 2%).

Miscellaneous

Pain (1% to 2%); angioedema, chest pain, edema, hepatocellular and cholestatic liver injury (including jaundice) (postmarketing).

Precautions

Monitor Monitor patient for orthostatic hypotension. Assess changes in urinary symptoms such as dribbling, frequency, hesitancy, nocturia, volume, and weak stream.

Pregnancy

Category B .

Lactation

Use not indicated.

Children

Not indicated for use in children.

Renal Function

Use with caution in patients with severe renal impairment.

Hepatic Function

Contraindicated in patients with moderate or severe hepatic impairment.

Coronary insufficiency

Discontinue if symptoms of angina pectoris appear or worsen.

Hypotension

Postural hypotension with or without symptoms may occur within a few hours following administration of alfuzosin.

Intraoperative floppy iris syndrome

Has been observed during cataract surgery in some patients on or previously treated with alpha-1 blockers.

Prostate carcinoma

Rule out presence of carcinoma of the prostate before starting alfuzosin.

QT prolongation

Use with caution and monitor patients with a known history of QT prolongation or patients taking medication known to prolong the QT interval.

Overdosage

Symptoms

Hypotension.

Patient Information

• Advise patient to take prescribed dose every day immediately after the same meal each day.
• Advise patient not to cut, crush, or chew tablet and to swallow the tablet whole with a full glass of water.
• Caution patient to avoid sudden position changes to prevent orthostatic hypotension.
• Caution patient that drug may cause dizziness or fainting and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
• Advise patient to contact health care provider if urinary symptoms do not improve or if they worsen.
• Instruct patient to report the following symptoms to health care provider: chest pain, dizziness, fainting, prolonged or painful erection, or other bothersome side effects.
• Advise patients to tell their ophthalmologist about their use of alfuzosin before cataract surgery or other procedures involving the eyes.

Copyright © 2009 Wolters Kluwer Health.