Uroxatral Description

Each UROXATRAL (alfuzosin HCl extended-release tablets) tablet contains 10 mg alfuzosin hydrochloride 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 empirical formula of alfuzosin hydrochloride is C19 H27 N5 O4 ?HCl. The molecular weight of alfuzosin hydrochloride is 425.9. Its structural formula is:

The tablet also contains the following inactive ingredients: colloidal silicon dioxide (NF), ethylcellulose (NF), hydrogenated castor oil (NF), hydroxypropyl methylcellulose (USP), magnesium stearate (NF), mannitol (USP), microcrystalline cellulose (NF), povidone (USP), and yellow ferric oxide (NF).

Uroxatral Indications And Usage

UROXATRAL (alfuzosin HCl extended-release tablets) is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia. UROXATRAL is not indicated for the treatment of hypertension.

Uroxatral Contraindications

UROXATRAL should not be used in patients with moderate or severe hepatic insufficiency, (Childs-Pugh categories B and C) since alfuzosin blood levels are increased in these patients. (See CLINICAL PHARMACOLOGY, Patients with Hepatic Insufficiency subsection.)

UROXATRAL should not be co-administered with potent CYP3A4 inhibitors such as ketoconazole, itraconazole, and ritonavir, since alfuzosin blood levels are increased. (See CLINICAL PHARMACOLOGY).

UROXATRAL (alfuzosin HCl extended-release tablets) is contraindicated in patients known to be hypersensitive to alfuzosin hydrochloride or any component of UROXATRAL tablets.

Uroxatral Side Effects

Postural hypotension with or without symptoms (e.g., dizziness) may develop within a few hours following administration of UROXATRAL (alfuzosin HCl extended-release tablets). As with other alpha-blockers, 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. Care should be taken when UROXATRAL is administered to patients with symptomatic hypotension or patients who have had a hypotensive response to other medications.

Uroxatral Precautions

General

Prostatic Carcinoma

Carcinoma of the prostate and BPH cause many of the same symptoms. These two diseases frequently coexist. Therefore, patients thought to have BPH should be examined prior to starting therapy with UROXATRAL (alfuzosin HCl extended-release tablets) to rule out the presence of carcinoma of the prostate.

Intraoperative Floppy Iris Syndrome (Ifis)

IFIS has been observed during cataract surgery in some patients on or previously treated with alpha-1 blockers. 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-1 blocker therapy prior to cataract surgery.

Drug-drug Interactions

The pharmacokinetic and pharmacodynamic interactions between UROXATRAL and other alpha-blockers have not been determined. However, interactions may be expected, and UROXATRAL should NOT be used in combination with other alpha-blockers.

Coronary Insufficiency

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

Hepatic Insufficiency

UROXATRAL should not be given to patients with moderate or severe hepatic insufficiency. (See CONTRAINDICATIONS ). The pharmacokinetics of UROXATRAL have not been studied in patients with mild hepatic insufficiency (See CLINICAL PHARMACOLOGY, Patients with Hepatic Insufficiency).

Renal Insufficiency

Systemic exposure was increased by approximately 50% in pharmacokinetic studies of patients with mild, moderate, and severe renal insufficiency (See CLINICAL PHARMACOLOGY, Special Populations). In phase 3 studies, the safety profile of patients with mild (n=172) or moderate (n=56) renal impairment was similar to the patients with normal renal function in those studies. Safety data are available in only a limited number of patients (n=6) with creatinine clearance below 30 mL/min; therefore, caution should be exercised when UROXATRAL is administered in patients with severe renal insufficiency.

Patients With Congenital Or Acquired Qt Prolongation

In a study of QT effect in 45 healthy males (See CLINICAL PHARMACOLOGY, Electrophysiology), the QT effect appeared less with alfuzosin 10 mg than with 40 mg, and the effect of alfuzosin 40 mg did not appear as large as that of the active control moxifloxacin at its therapeutic dose. A post-marketing study evaluating the effect of combining UROXATRAL with another drug of comparable QT effect showed an increased effect when compared to either drug alone. (See CLINICAL PHARMACOLOGY, Electrophysiology) Although this study was not designed to make direct statistical comparisons between drugs, the QT increase with both drugs was no more than additive and was lower than that of the active control moxifloxacin. These observations should be considered in clinical decisions when prescribing UROXATRAL for patients with a known history of QT prolongation or patients who are taking medications which prolong the QT interval. There has been no signal of Torsades de Pointe in the extensive post-marketing experience with alfuzosin. There are no known PK/PD studies of the effects of other alpha-blockers on cardiac repolarization.

Information For Patients

Patients should be told about the possible occurrence of symptoms related to postural hypotension, such as dizziness, when beginning UROXATRAL, and they should be cautioned about driving, operating machinery, or performing hazardous tasks during this period.

UROXATRAL should be taken with food and with the same meal each day.

Patients should be advised not to crush or chew UROXATRAL tablets.

Laboratory Tests

No laboratory test interactions with UROXATRAL tablets are known.

Pediatric Use

UROXATRAL is not indicated for use in children.

Geriatric Use

Of the total number of subjects in clinical studies of UROXATRAL, 48% were 65 years of age and over, whereas 11% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. (See CLINICAL PHARMACOLOGY, Elderly subsection.)

Carcinogenesis, Mutagenesis, and 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 level of exposure to humans 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 level of exposure to humans based on AUC of unbound drug) 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 given alfuzosin at daily oral (gavage) doses of up to 250 mg/kg/day for 26 weeks, which corresponds to levels of exposure several hundred times that in humans. 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 doses of 25 mg/kg and 20 mg/kg, respectively, corresponding to levels of systemic exposure (based on AUC of unbound drug) 12- and 18-fold higher, respectively, than in humans, although this did not result in impaired fertility in rats.

Pregnancy

Teratogenic Effects, Pregnancy and Lactation Category B.

UROXATRAL is not indicated for use in women.

There was no evidence of teratogenicity or embryotoxicity in rats at maternal (oral gavage) doses up to 250 mg/kg/day, corresponding to systemic exposure levels 1,200-fold higher than in humans. In rabbits, up to the dose of 100 mg/kg/day (approximately 3 times the clinical dose by body surface area) given orally (via gavage), no evidence of fetal toxicity or teratogenicity was seen.

Gestation was slightly prolonged in rats with a maternal dose >5 mg/kg/day (oral gavage), which corresponds to systemic exposure levels (based on AUC of unbound drug) 12 times higher than human exposure levels, but there were no difficulties with parturition.

Nursing Mothers

UROXATRAL is not indicated for use in women.

Uroxatral Overdosage

Should overdose of UROXATRAL (alfuzosin HCl extended-release tablets) lead to hypotension, support of the cardiovascular system is of first importance. Restoration of blood pressure and normalization of heart rate may be accomplishedby keeping the patient in the supine position. If this measure is inadequate, then the administration of intravenous fluids should be considered. If necessary, vasopressors should then be used, and the renal function should be monitored and supported as needed. Alfuzosin is 82% to 90% proteinbound; therefore, dialysis may not be of benefit.

Uroxatral Information For Patients

Patients should be told about the possible occurrence of symptoms related to postural hypotension, such as dizziness, when beginning UROXATRAL, and they should be cautioned about driving, operating machinery, or performing hazardous tasks during this period.

UROXATRAL should be taken with food and with the same meal each day.

Patients should be advised not to crush or chew UROXATRAL tablets.

Uroxatral Patient InformationuroxatralŽ(Alfuzosin Hydrochlorideextended-release Tablets)

Read the Patient Information that comes with UROXATRAL before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your condition or your treatment. You and your doctor should talk about all your medicines, including UROXATRAL, now and at your regular checkups.

What is the most important information I should know about UROXATRAL?

UROXATRAL can cause :

• a sudden drop in blood pressure, especially when you start treatment. This may lead to fainting, dizziness, or lightheadedness. Do not drive, operate machinery, or do any dangerous activities until you know how UROXATRAL affects you. This is especially important if you already have a problem with low blood pressure or take medicines to treat high blood pressure. If you begin to feel dizzy or lightheaded, lie down with your legs and feet up, and if your symptoms do not improve call your doctor.

What is UROXATRAL?

UROXATRAL is a prescription medicine that is called an "alpha-blocker". UROXATRAL is used in adult men to treat the symptoms of benign prostatic hyperplasia (BPH). UROXATRAL may help to relax the muscles in the prostate and the bladder which may lessen the symptoms of BPH and improve urine flow.

Before prescribing UROXATRAL, your doctor may examine your prostate gland and do a blood test called a prostate specific antigen (PSA) test to check for prostate cancer. Prostate cancer and BPH can cause the same symptoms. Prostate cancer needs a different treatment.

UROXATRAL is not for use in women or children.

Some medicines called "alpha-blockers" are used to treat high blood pressure. UROXATRAL has not been studied for the treatment of high blood pressure.

Who should not take UROXATRAL?

Do not take UROXATRAL if you:

• have liver problems
• are taking antifungal drugs like ketoconazole or HIV drugs called protease inhibitors
• are already taking an alpha-blocker for either high blood pressure or prostate problems
• are a woman
• are a child under the age of 18
• are allergic to UROXATRAL The active ingredient is alfuzosin hydrochloride. See the end of this leaflet for a complete list of ingredients in UROXATRAL.

Before taking UROXATRAL, tell your doctor:

• if you have liver problems
• if you have kidney problems
• if you or any family members have a rare heart condition known as congenital prolongation of the QT interval.
• about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. Some of your other medicines may affect the way you respond or react to UROXATRAL.
• if you have had low blood pressure, especially after taking another medicine. Signs of low blood pressure are fainting, dizziness, and lightheadedness.
• if you have a heart problem called angina (pain in your chest, jaw, or arm).

What you need to know while taking UROXATRAL (alfuzosin HCl) tablets

• If you have an eye surgery for cataract (clouding of the eye) planned, tell your ophthalmologist that you are using UROXATRAL or have previously been treated with an alpha-blocker.

How do I take UROXATRAL?

• Take UROXATRAL exactly as your doctor prescribes it.
• Take one UROXATRAL tablet after the same meal each day. UROXATRAL should be taken just after eating food. Do not take it on an empty stomach.
• Swallow the UROXATRAL tablet whole. Do not crush, split, or chew UROXATRAL tablets.
• If you take too much UROXATRAL call your local poison control center or emergency room right away.

What are the possible side effects of UROXATRAL?

The most common side effects with UROXATRAL are:

• dizziness
• headache
• tiredness

Call your doctor if you get any side effect that bothers you.

These are not all the side effects of UROXATRAL. For more information ask your doctor or pharmacist.

How do I store UROXATRAL?

Store UROXATRAL between 59°F and 86°F (15°C and 30°C).

Protect from light and moisture.

Keep UROXATRAL and all medicines out of the reach of children.

General information about UROXATRAL:

Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not use UROXATRAL for a condition for which it was not prescribed. Do not give UROXATRAL to other people, even if they have the same symptoms you have. It may harm them.

This leaflet summarizes the most important information about UROXATRAL. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about UROXATRAL that is written for health professionals.

You may also visit our website at www.UROXATRAL.com or call 1-800-446-6267.

What are the ingredients of UROXATRAL?

Active Ingredient : alfuzosin hydrochloride

Inactive Ingredients : colloidal silicon dioxide (NF), ethylcellulose (NF), hydrogenated castor oil (NF), hydroxypropyl methylcellulose (USP), magnesium stearate (NF), mannitol (USP), microcrystalline cellulose (NF), povidone (USP), and yellow ferric oxide (NF).