UROXATRAL is indicated for the treatment of signs and symptoms of benign prostatic hyperplasia.

UROXATRAL is an alpha adrenergic antagonist, indicated for the treatment of signs and symptoms of benign prostatic hyperplasia. (1)

Important Limitations of Use:
UROXATRAL is not indicated for treatment of hypertension. (1.1)
UROXATRAL is not indicated for use in the pediatric population. (1.1, 8.4, 12.3)

UROXATRAL is not indicated for the treatment of hypertension.
UROXATRAL is not indicated for use in the pediatric population.

The recommended dosage is one 10 mg UROXATRAL (alfuzosin HCl) extended-release tablet once daily. The extent of absorption of alfuzosin is 50% lower under fasting conditions. Therefore, Uroxatral should be taken with food and with the same meal each day. The tablets should not be chewed or crushed.

10 mg once daily with food and with the same meal each day. (2)

Tablets should not be chewed or crushed (2, 12.3)

UROXATRAL is contraindicated for use:

• in patients with moderate or severe hepatic impairment (Childs-Pugh categories B and C), since alfuzosin blood levels are increased in these patients [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
• with potent CYP3A4 inhibitors such as ketoconazole, itraconazole, and ritonavir, since alfuzosin blood levels are increased [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].
• in patients with known hypersensitivity, such as urticaria and angioedema, to alfuzosin hydrochloride or any component of UROXATRAL tablets [see Adverse Reactions (6.2)]

• Moderate or severe hepatic impairment (4, 8.7, 12.3)
• Co-administration with potent CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, ritonavir) (4, 5.4, 7.1, 12.3)
• Known hypersensitivity (e.g., urticaria or angioedema) to alfuzosin or any of the ingredients (4, 6.2)

• Postural hypotension/syncope: Care should be taken in patients with symptomatic hypotension or who have had a hypotensive response to other medications or are concomitantly treated with antihypertensive medication or nitrates (5.1)
• Use with caution in patients with severe renal impairment (creatinine clearance <30 mL/min) (5.2, 8.6, 12.3)
• Use with caution in patients with mild hepatic impairment (5.3, 8.7, 12.3)
• Should not be used in combination with other alpha adrenergic antagonists (5.4, 7.2)
• Prostate carcinoma should be ruled out prior to treatment (5.5)
• Intraoperative Floppy Iris Syndrome (IFIS) during cataract surgery may require modifications to the surgical technique (5.6)
• Discontinue UROXATRAL if symptoms of angina pectoris appear or worsen (5.8)
• Use with caution in patients with a history of QT prolongation or who are taking medications which prolong the QT interval (5.9, 12.2)

Postural hypotension with or without symptoms (e.g., dizziness) may develop within a few hours following administration of UROXATRAL. As with other alpha adrenergic antagonists, there is a potential for syncope. Patients should be warned of the possible occurrence of such events and should avoid situations where injury could result should syncope occur. There may be an increased risk of hypotension/postural hypotension and syncope when taking UROXATRAL concomitantly with anti-hypertensive medication and nitrates. Care should be taken when UROXATRAL is administered to patients with symptomatic hypotension or patients who have had a hypotensive response to other medications.

Caution should be exercised when UROXATRAL is administered in patients with severe renal impairment (creatinine clearance < 30 mL/min) [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

UROXATRAL is contraindicated for use in patients with moderate or severe hepatic impairment [see Contraindications (4), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)]. Although the pharmacokinetics of UROXATRAL have not been studied in patients with mild hepatic impairment, caution should be exercised when UROXATRAL is administered to such patients [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].

Potent CYP3A4 Inhibitors: UROXATRAL is contraindicated for use with potent CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, ritonavir) since alfuzosin blood levels are increased [see Contraindications (4), Drug Interactions (7.1) and Clinical Pharmacology (12.3)].

Other alpha adrenergic antagonists: UROXATRAL is an alpha adrenergic antagonist and should not be used in combination with other alpha adrenergic antagonist [see Drug Interactions (7.2)].

Phosphodiesterase-5 (PDE5) Inhibitors: PDE5-inhibitors are also vasodilators. Caution is advised for concomitant use of PDE5-inhibitors and UROXATRAL, as this combination can potentially cause symptomatic hypotension [see Drug Interactions (7.4)].

Carcinoma of the prostate and benign prostatic hyperplasia (BPH) cause many of the same symptoms. These two diseases frequently coexist. Therefore, patients thought to have BPH should be examined to rule out the presence of carcinoma of the prostate prior to starting treatment with UROXATRAL.

IFIS has been observed during cataract surgery in some patients on or previously treated with alpha adrenergic antagonists. This variant of small pupil syndrome is characterized by the combination of a flaccid iris that billows in response to intraoperative irrigation currents, progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs, and potential prolapse of the iris toward the phacoemulsification incisions. The patient's ophthalmologist should be prepared for possible modifications to their surgical technique, such as the utilization of iris hooks, iris dilator rings, or viscoelastic substances.

There does not appear to be a benefit of stopping alpha adrenergic antagonist therapy prior to cataract surgery.

Rarely (probably less than 1 in 50,000), alfuzosin, like other alpha adrenergic antagonists, has been associated with priapism (persistent painful penile erection unrelated to sexual activity). Because this condition can lead to permanent impotence if not properly treated, patients should be advised about the seriousness of the condition [see Adverse Reactions (6.2) and Patient Counseling Information [17.3]).

If symptoms of angina pectoris should appear or worsen, UROXATRAL should be discontinued.

Use with caution in patients with acquired or congenital QT prolongation or who are taking medications that prolong the QT interval [see Clinical Pharmacology (12.2)].

Most common adverse reactions in clinical studies (incidence ≥2% and at a higher incidence than placebo): dizziness, upper respiratory tract infection, headache, fatigue. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Advanz Pharma (US) Corp. at 1-877-370-1142 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The incidence of adverse reactions has been ascertained from 3 placebo-controlled clinical trials involving 1,608 men where daily doses of 10 and 15 mg alfuzosin were evaluated. In these 3 trials, 473 men received UROXATRAL (alfuzosin HCl) 10 mg extended-release tablets. In these trials, 4% of patients taking UROXATRAL (alfuzosin HCl) 10 mg extended-release tablets withdrew from the trial due to adverse reactions, compared with 3% in the placebo group.

Table 1 summarizes adverse reactions that occurred in ≥2% of patients receiving UROXATRAL, and at a higher incidence than that of the placebo group. In general, the adverse reactions seen in long-term use were similar in type and frequency to the events described below for the 3-month trials.

Table 1 — Adverse Reactions Occurring in ≥2% of UROXATRAL-Treated Patients and More Frequently than with Placebo in 3-Month Placebo-Controlled Clinical Trials

Adverse Reaction	Placebo (n=678)	UROXATRAL (n=473)
Dizziness	19 (2.8%)	27 (5.7%)
Upper respiratory tract infection	4 (0.6%)	14 (3.0%)
Headache	12 (1.8%)	14 (3.0%)
Fatigue	12 (1.8%)	13 (2.7%)

The following adverse reactions, reported by between 1% and 2% of patients receiving UROXATRAL and occurring more frequently than with placebo, are listed alphabetically by body system and by decreasing frequency within body system:

Body as a whole: pain

Gastrointestinal system: abdominal pain, dyspepsia, constipation, nausea

Reproductive system: impotence

Respiratory system: bronchitis, sinusitis, pharyngitis

Signs and Symptoms of Orthostasis in Clinical Trials: The adverse reactions related to orthostasis that occurred in the double-blind phase 3 trials with alfuzosin 10 mg are summarized in Table 2. Approximately 20% to 30% of patients in these trials were taking antihypertensive medication.

Table 2— Number (%) of Patients with Symptoms Possibly Associated with Orthostasis in 3-Month Placebo-Controlled Clinical Trials

Symptoms	Placebo (n=678)	UROXATRAL (n=473)
Dizziness	19 (2.8%)	27 (5.7%)
Hypotension or postural hypotension	0	2 (0.4%)
Syncope	0	1 (0.2%)

Testing for blood pressure changes or orthostatic hypotension was conducted in three controlled studies. Decreased systolic blood pressure (≤90 mm Hg, with a decrease ≥20 mm Hg from baseline) was observed in none of the 674 placebo patients and 1 (0.2%) of the 469 UROXATRAL patients. Decreased diastolic blood pressure (≤50 mm Hg, with a decrease ≥15 mm Hg from baseline) was observed in 3 (0.4%) of the placebo patients and in 4 (0.9%) of the UROXATRAL patients. A positive orthostatic test (decrease in systolic blood pressure of ≥20 mm Hg upon standing from the supine position) was seen in 52 (7.7%) of placebo patients and in 31 (6.6%) of the UROXATRAL patients.

The following adverse reactions have been identified during post approval use of UROXATRAL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

General disorders: edema

Cardiac disorders: tachycardia, chest pain, angina pectoris in patients with pre-existing coronary artery disease, atrial fibrillation

Gastrointestinal disorders: diarrhea, vomiting

Hepatobiliary disorders: hepatocellular and cholestatic liver injury (including cases with jaundice leading to drug discontinuation)

Respiratory system disorders: rhinitis

Reproductive system disorders: priapism

Skin and subcutaneous tissue disorders: rash, pruritis, urticaria, angioedema, toxic epidermal necrolysis

Vascular disorders: flushing

Blood and lymphatic system disorders: thrombocytopenia

During cataract surgery, a variant of small pupil syndrome known as Intraoperative Floppy Iris Syndrome (IFIS) has been reported in some patients on or previously treated with alpha adrenergic antagonists [see Warnings and Precautions (5.6)].