1 INDICATIONS AND USAGE

Alfuzosin hydrochloride extended-release tablets are indicated for the treatment of signs and symptoms of benign prostatic hyperplasia.

1.1 Important Limitations of Use

Alfuzosin hydrochloride extended-release tabletsare not indicated for the treatment of hypertension.

Alfuzosin hydrochloride extended-release tablets are not indicated for use in the pediatric population.

5 WARNINGS AND PRECAUTIONS

5.1 Postural Hypotension

Postural hypotension with or without symptoms (e.g., dizziness) may develop within a few hours following administration of alfuzosin hydrochloride extended-release tablets. 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 alfuzosin hydrochloride extended-release tablets concomitantly with anti-hypertensive medication and nitrates. Care should be taken when alfuzosin hydrochloride extended-release tablets are administered to patients with symptomatic hypotension or patients who have had a hypotensive response to other medications.

5.2 Patients with Renal Impairment

Caution should be exercised when alfuzosin hydrochloride extended-release tablets are administered in patients with severe renal impairment (creatinine clearance < 30 mL/min) [see Use in Specific Populations ( 8.6) and Clinical Pharmacology ( 12.3)] .

5.3 Patients with Hepatic Impairment

Alfuzosin hydrochloride extended-release tablets are 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 alfuzosin hydrochloride extended-release tablets have not been studied in patients with mild hepatic impairment, caution should be exercised when alfuzosin hydrochloride extended-release tablets are administered to such patients [see Use in Specific Populations ( 8.7) and Clinical Pharmacology ( 12.3)] .

5.4 Drug-Drug Interactions

Potent CYP3A4 Inhibitors: Alfuzosin hydrochloride 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:**Alfuzosin hydrochloride 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 alfuzosin hydrochloride, as this combination can potentially cause symptomatic hypotension [see Drug Interactions ( 7.4)].

5.5 Prostatic Carcinoma

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 alfuzosin hydrochloride extended-release tablets.

5.6 Intraoperative Floppy Iris Syndrome (IFIS)

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.

5.7 Priapism

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)].

5.8 Coronary Insufficiency

If symptoms of angina pectoris should appear or worsen, alfuzosin hydrochloride extended-release tablets should be discontinued.

5.9 Patients with Congenital or Acquired QT Prolongation

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)].

11 DESCRIPTION

Each alfuzosin hydrochloride extended-release tablet, USP contains 10 mg alfuzosin hydrochloride, USP as the active ingredient. Alfuzosin hydrochloride is a white to off-white crystalline powder that melts at approximately 240°C. It is freely soluble in water, sparingly soluble in alcohol, and practically insoluble in dichloromethane.
Alfuzosin hydrochloride is (R,S)-N-[3-[(4-amino-6,7-dimethoxy-2-quinazolinyl) methylamino] propyl] tetrahydro-2-furancarboxamide hydrochloride. The molecular formula of alfuzosin hydrochloride is C 19H 27N 5O 4•HCl. The molecular weight of alfuzosin hydrochloride is 425.9.
Its structural formula is:


The tablet also contains the following inactive ingredients: pregelatinized maize starch, hypromellose, hydroxypropyl cellulose, basic butylated methacrylate copolymer, colloidal silicon dioxide, magnesium stearate, and talc.

Meets USP Dissolution Test 7.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

There was no evidence of a drug-related increase in the incidence of tumors in mice following dietary administration of 100 mg/kg/day alfuzosin for 98 weeks (13 and 15 times the maximum recommended human dose [MRHD] of 10 mg based on AUC of unbound drug), in females and males, respectively. The highest dose tested in female mice may not have constituted a maximally tolerated dose. Likewise, there was no evidence of a drug-related increase in the incidence of tumors in rats following dietary administration of 100 mg/kg/day alfuzosin for 104 weeks (53 and 37 times the MRHD in females and males, respectively).

Alfuzosin showed no evidence of mutagenic effect in the Ames and mouse lymphoma assays, and was free of any clastogenic effects in the Chinese hamster ovary cell and in vivo mouse micronucleus assays. Alfuzosin treatment did not induce DNA repair in a human cell line.

There was no evidence of reproductive organ toxicity when male rats were administered oral doses of several hundred times (250 mg/kg/day for 26 weeks) the MRHD of alfuzosin. No impairment of fertility was observed following oral (gavage) administration to male rats at doses of up to 125 mg/kg/day for 70 days. Estrous cycling was inhibited in rats and dogs at approximately 12 and 18 times the MRHD respectively (doses of 25 mg/kg and 20 mg/kg, respectively), but did not result in impaired fertility in female rats.

17 PATIENT COUNSELING INFORMATION

See FDA-approved patient labeling.

17.1 Hypotension/Syncope

Patients should be told about the possible occurrence of symptoms related to postural hypotension, such as dizziness, when beginning alfuzosin hydrochloride extended-release tablets, and they should be cautioned about driving, operating machinery, or performing hazardous tasks during this period. This is important for those with low blood pressure or who are taking antihypertensive medications or nitrates [see Warnings and Precautions ( 5.1)] .

17.2 Intraoperative Floppy Iris Syndrome

Patients should be instructed to tell their ophthalmologist about their use of alfuzosin hydrochloride extended-release tablets before cataract surgery or other procedures involving the eyes, even if the patient is no longer taking alfuzosin hydrochloride extended-release tablets [see Warnings and Precautions ( 5.6)] .

17.3 Priapism

Patients should be advised about the possibility of priapism resulting from treatment with alfuzosin hydrochloride extended-release tablets and medications in the same class. Although this reaction is extremely rare, but if not brought to immediate medical attention, can lead to permanent erectile dysfunction (impotence) [see Warnings and Precautions ( 5.7)] .

17.4 Instructions of Use

Alfuzosin hydrochloride extended-release tablets should be taken with food and with the same meal each day. Patients should be advised not to crush or chew alfuzosin hydrochloride extended-release tablets.