Cardura XL

Doxazosin may cause side effects. Tell your doctor if any of these symptoms or those listed in the SPECIAL PRECAUTIONS section are severe or do not go away:

• headache
• tiredness
• swelling of the hands, feet, ankles, or lower legs
• shortness of breath
• weight gain
• muscle or joint pain or weakness
• abnormal vision
• runny nose
• decreased sexual ability

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately or seek emergency medical treatment:

• rapid, pounding, or irregular heartbeat
• chest pain
• shortness of breath
• hives
• painful erection of the penis that lasts for hours

Doxazosin may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Cardura XL , there are no specific foods that you must exclude from your diet when receiving this medication.

Tell your doctor if you are breastfeeding or planning to breastfeed.

It is not known whether Cardura XL crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using Cardura XL.

• Take Cardura XL exactly as prescribed.
• Cardura XL comes in an extended-release tablet form and is taken once a day in the morning with breakfast.
• Swallow Cardura XL tablets whole. Do not chew, divide, cut or crush tablets.
• If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of Cardura XL at the same time.

Doxazosin is an alpha-adrenergic (AL-fa ad-ren-ER-jik) blockers. Doxazosin relaxes your veins and arteries so that blood can more easily pass through them. It also relaxes the muscles in the prostate and bladder neck, making it easier to urinate.

Doxazosin is used to treat hypertension (high blood pressure), or to improve urination in men with benign prostatic hyperplasia (enlarged prostate).

The extended-release form of doxazosin (Cardura XL) is for use only in treating benign prostatic hyperplasia and should not be used to treat hypertension.

Doxazosin may also be used for purposes not listed in this medication guide.

In the U.S.

• Cardura
• Cardura XL

Available Dosage Forms:

• Tablet, Extended Release
• Tablet

Therapeutic Class: Cardiovascular Agent

Pharmacologic Class: Alpha-1 Adrenergic Blocker

• Tell all of your health care providers that you take Cardura XL. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine affects you.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• Have your blood pressure checked often. Talk with your doctor.
• If you are having cataract surgery or other eye procedure, talk with your doctor.
• If taking for an enlarged prostate, have a rectal exam (to check prostate gland) and blood work (PSA test) as you have been told by the doctor.
• If you are taking Cardura XL and have high blood pressure, talk with your doctor before using OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.
• You may see something that looks like the tablet in your stool. This is normal and not a cause for concern. If you have questions, talk with your doctor.
• If you are 70 years or older, use this medicine with care. You could have more side effects.

Use Cardura XL as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with breakfast.
• Swallow whole. Do not chew, break, or crush.
• If you have trouble swallowing, talk with your doctor.
• To gain the most benefit, do not miss doses.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.
• If you miss taking Cardura XL for a few days in a row, call your doctor before you start taking it again.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Very bad dizziness or passing out.
• Chest pain that is new or worse.
• Shortness of breath.
• Swelling in the arms or legs.
• Call your doctor right away if you have a painful erection (hard penis) or an erection that lasts for longer than 4 hours. This may happen even when you are not having sex. If this is not treated right away, it may lead to lasting sex problems and you may not be able to have sex.

Postural Hypotension

Postural hypotension with or without symptoms (e.g., dizziness) may develop within a few hours following administration of Cardura XL. However, infrequently, symptomatic postural hypotension has also been reported later than a few hours after dosing. As with other alpha-blockers, there is a potential for syncope, especially after the initial dose or after an increase in dosage strength. 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 Cardura XL is administered to patients with symptomatic hypotension or patients who have had a hypotensive response to other medications.

Cataract Surgery

Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in some patients on or previously treated with alpha1 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 surgeon 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 from stopping alpha1 blocker therapy prior to cataract surgery.

Gastrointestinal Disorders

As with any other non-deformable material, caution should be used when administering Cardura XL to patients with preexisting severe gastrointestinal narrowing (pathologic or iatrogenic). There have been rare reports of obstructive symptoms in patients with known strictures in association with the ingestion of another drug in this non-deformable extended release formulation. Markedly increased GI retention times, as may occur in patients with chronic constipation, can increase systemic exposure to doxazosin and thereby potentially increase adverse reactions.

Prostate Cancer

Carcinoma of the prostate causes many of the same symptoms associated with BPH and the two disorders frequently co-exist. Carcinoma of the prostate should therefore be ruled out prior to commencing therapy with Cardura XL.

PDE-5 Inhibitors

Concomitant administration of Cardura XL with a PDE-5 inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension. Pharmacodynamic interactions between Cardura XL and antihypertensive medications or other vasodilating agents have not been determined.

Patients with Hepatic Impairment

Cardura XL is not recommended for patients with severe hepatic impairment and should be administered with caution to patients with mild or moderate hepatic impairment [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

Patients with Coronary Insufficiency

Patients with congestive heart failure, angina pectoris, or acute myocardial infarction within the last 6 months were excluded from the Phase 3 studies. If symptoms of angina pectoris should newly appear or worsen, Cardura XL should be discontinued.

CYP 3A4 Inhibitors

Caution should be exercised when concomitantly administering Cardura XL with a strong CYP 3A4 inhibitor, such as atanazavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, or voriconazole.

Priapism

Rarely (probably less frequently than once in every several thousand patients), alpha-1 antagonists, including doxazosin, have been associated with priapism (painful penile erection, sustained for hours and unrelieved by sexual intercourse or masturbation). Because this condition can lead to permanent impotence if not promptly treated, patients must be advised about the seriousness of the condition.

Cardura XL contains doxazosin mesylate which is a quinazoline compound with the chemical name 1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(1,4-benzodioxan-2-ylcarbonyl) piperazine methanesulfonate. The empirical formula for doxazosin mesylate is C23H25N5O5 • CH4O3S and the molecular weight is 547.6. It has the following structure:

Cardura XL is an extended release tablet for oral use and is designed to deliver 4 or 8 mg of doxazosin as the free base. Each 4 and 8 mg tablet contains 5.1 and 10.2 mg doxazosin mesylate (includes a 5% overage) to provide 4 and 8 mg doxazosin as a free base, respectively. The inactive ingredients for Cardura XL are: polyethylene oxide, sodium chloride, hypromellose, red ferric oxide, titanium dioxide, magnesium stearate, cellulose acetate, Macrogol®, pharmaceutical glaze, and black iron oxide.

Cardura XL System Components and Performance

Cardura XL is similar in appearance to a conventional tablet. It consists, however, of an osmotically active drug core surrounded by a semipermeable membrane. The core itself is divided into two layers: an "active" layer containing the drug, and a "push" layer containing pharmacologically inert (but osmotically active) components. The membrane surrounding the tablet is permeable to water, but not to drug or osmotic excipients. As water from the gastrointestinal tract enters the tablet, pressure increases in the osmotic layer and "pushes" against the drug layer, resulting in the release of drug through a small, laser-drilled orifice in the membrane on the drug side of the tablet.

Cardura XL utilizes GITS (Gastrointestinal Therapeutic System) which is designed to provide a controlled rate of delivery of doxazosin into the gastrointestinal lumen which is independent of pH or gastrointestinal (GI) motility. The function of Cardura XL depends upon the existence of an osmotic gradient between the contents of the bi-layer core and fluid in the GI tract. Drug delivery is essentially constant as long as the osmotic gradient remains constant, and then gradually falls to zero. The biologically inert components of the tablet remain intact during GI transit and are eliminated in the feces as an insoluble shell.