Doxazosin

Before taking doxazosin,

• tell your doctor and pharmacist if you are allergic to doxazosin, prazosin (Minipress), terazosin, any other medications, or any ingredients in doxazosin tablets or extended-release tablets. Ask your pharmacist for a list of the ingredients..
• tell your doctor and pharmacist what prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: antihistamines; clarithromycin (Biaxin, in Prevpac); ipratropium (Atrovent, in Combivent); itraconazole (Onmel, Sporanox); ketoconazole (Nizoral); medications for erectile dysfunction (ED) such as sildenafil (Revatio, Viagra), tadalafil (Adcirca, Cialis), or vardenafil (Levitra, Staxyn); medications for high blood pressure; medications for HIV/AIDS including atazanavir (Reyataz), indinavir (Crixivan), nelfinavir (Viracept), ritonavir (Norvir, in Kaletra), or saquinavir (Invirase); medications for irritable bowel disease, motion sickness, Parkinson's disease, ulcers, or urinary problems; nefazodone; telithromycin (Ketek); and voriconazole (Vfend). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have angina (chest pain); low blood pressure; if you have ever had low blood pressure after taking a medication; or if you have or have ever had prostate cancer, or liver disease. If you are taking the extended-release tablet, tell you doctor if you have constipation, short bowel syndrome (a condition where more than half of the small intestine has been removed by surgery or damaged by disease), or narrowing or a blockage of the intestines.
• tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking doxazosin, call your doctor.
• talk to your doctor about the risks and benefits of taking doxazosin if you are 65 years of age or older. Older adults should not usually take doxazosin because it is not as safe as other medications that can be used to treat the same conditions.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking doxazosin. If you need to have eye surgery at any time during or after your treatment, be sure to tell your doctor that you are taking or have taken doxazosin.
• you should know that doxazosin may make you drowsy or dizzy. Do not drive a car, operate machinery, or perform dangerous tasks for 24 hours after the first time you take doxazosin or after your dose is increased.
• you should know that doxazosin may cause dizziness, lightheadedness, and fainting when you get up too quickly from a lying position. This is more common when you first start taking doxazosin, when your dose is increased, or if your treatment has been stopped for more than a few days. To avoid this problem, get out of bed slowly, resting your feet on the floor for a few minutes before standing up. If you experience these symptoms, sit or lie down. If these symptoms do not improve, call your doctor.

• Cardura^®
• Cardura^® XL

Serious side effects have been reported including:

• Extremely rarely, doxazosin and similar medications have caused painful erection of the penis, sustained for hours and unrelieved by sexual intercourse or masturbation. This condition, known medically as priapism, is serious, and if untreated it can be followed by permanent inability to have an erection. If you have a prolonged abnormal erection, call your doctor or go to an emergency room as soon as possible.
• If you plan to have surgery for cataracts (clouding of the eye), tell your surgeon if you take or have taken doxazosin. During cataract surgery, a condition called Intraoperative Floppy Iris Syndrome (IFIS) can happen if you take or have taken doxazosin.
• Doxazosin lowers blood pressure and may cause dizziness or fainting, especially when you first start taking it, or when you start taking it again. Call your doctor if you have severe dizziness or feel like you might pass out.

Doxazosin can cause drowsiness. Do not drive or operate heavy machinery until you know how doxazosin affects you.

Do not take doxazosin if you:

• are allergic to doxazosin or any inactive ingredient in this medication
• are allergic to any of the medications related to doxazosin such as alfuzosin (Uroxatral), prazosin (Minipress), and terazosin (Hytrin)

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Doxazosin falls into category C. There are no good studies in pregnant women. Doxazosin should be used during pregnancy only if the possible benefit outweighs the possible risk to the unborn baby.

In the U.S.

• Cardura
• Cardura XL

Available Dosage Forms:

• Tablet, Extended Release
• Tablet

Therapeutic Class: Cardiovascular Agent

Pharmacologic Class: Alpha-1 Adrenergic Blocker

Postural Hypotension

Postural hypotension with or without symptoms (e.g., dizziness) may develop within a few hours following administration of Doxazosin. 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. Advise patient how to avoid symptoms resulting from postural hypotension and what measures to take should they develop.

Concomitant administration of Doxazosin with a PDE-5 inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension.

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 of stopping alpha1 blocker therapy prior to cataract surgery.

Prostate Cancer

Carcinoma of the prostate causes many of the 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 Doxazosin for the treatment of BPH.

Priapism

Alpha1 antagonists, including Doxazosin, have been associated with priapism (painful penile erection, sustained for hours and unrelieved by sexual intercourse or masturbation). This condition can lead to permanent impotence if not promptly treated.

Pregnancy

Risk Summary

The limited available data with Doxazosin in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. However, untreated hypertension during pregnancy can result in increased maternal risks [see Clinical Considerations]. In animal reproduction studies, no adverse developmental effects were observed when Doxazosin was orally administered to pregnant rabbits and rats during the period of organogenesis at doses of up to 41 and 20 mg/kg, respectively (exposures in rabbits and rats were 10 and 4 times, respectively, the human AUC exposures with a 12 mg/day therapeutic dose). A dosage regimen of 82 mg/kg/day in the rabbit was associated with reduced fetal survival [see Data].

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Disease-associated maternal and/or embryo/fetal risk

Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death.

Data

Animal Data

Radioactivity was found to cross the placenta following oral administration of labelled Doxazosin to pregnant rats. Studies in pregnant rabbits and rats at daily oral doses of up to 41 and 20 mg/kg, respectively (plasma drug concentrations of 10 and 4 times, respectively, the human AUC exposures with a 12 mg/day therapeutic dose), have revealed no evidence of adverse developmental effects. A dosage regimen of 82 mg/kg/day in the rabbit was associated with reduced fetal survival. In peri- and postnatal studies in rats, postnatal development at maternal doses of 40 or 50 mg/kg/day of Doxazosin (about 8 times human AUC exposure with a 12 mg/day therapeutic dose) was delayed, as evidenced by slower body weight gain and slightly later appearance of anatomical features and reflexes.

Lactation

Risk Summary

There is limited information on the presence of Doxazosin in human milk [see Data]. There is no information on the effects of Doxazosin on the breastfeed infant or the effects on milk production.

Data

A single case study reports that Doxazosin is present in human milk, which resulted in an infant dose of less than 1% of the maternal weight-adjusted dosage and a milk/plasma ratio of 0.1. However, these data are insufficient to confirm the presence of Doxazosin in human milk.

Pediatric Use

The safety and effectiveness of Doxazosin have not been established in children.

Geriatric Use

Benign Prostatic Hyperplasia (BPH)

The safety and effectiveness profile of Doxazosin was similar in the elderly (age ≥ 65 years) and younger (age < 65 years) patients.

Hypertension

Clinical studies of Doxazosin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

Hepatic Impairment

Doxazosin is extensively metabolized in the liver. Hepatic impairment is expected to increase exposure to Doxazosin. Use of Doxazosin in patients with severe hepatic impairment (Child-Pugh Class C) is not recommended. Monitor blood pressure and for symptoms of hypotension in patients with lesser degrees of hepatic impairment (Child-Pugh Class A and B) [see Clinical Pharmacology (12.3)].

• Cardura
• Cardura XL

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include extreme dizziness or fainting.

Commonly reported side effects of doxazosin include: dizziness, fatigue, vertigo, hypertension, symptomatic orthostatic hypotension, malaise, and orthostatic effect. Other side effects include: syncope, drowsiness, edema, and dizziness. See below for a comprehensive list of adverse effects.

• Doxazosin blocks alpha-1 receptors. Stimulation of alpha-1 receptors is associated with a tightening up of the smooth muscle located in the prostate and neck of the bladder. This muscle tightening can detrimentally affect urine flow and frequency, and cause symptoms such as those seen in Benign Prostatic Hyperplasia (BPH). Doxazosin blocks these receptors allowing this muscle to relax.
• Doxazosin also lowers blood pressure by selectively blocking alpha-1 receptors located in the smooth muscle lining blood vessels, allowing the blood vessels to widen (dilate). Doxazosin may also block the nerve receptors responsible for the contraction (narrowing) of the blood vessels.
• Doxazosin belongs to the group of medicines known as alpha-1 adrenergic blockers (often shortened to alpha blockers).

• Doxazosin is usually given once daily.
• If you feel yourself beginning to faint or feeling dizzy or lightheaded while on doxazosin, lie down until the feeling passes. This effect is usually short-lived and likely only to occur on therapy initiation or during dose titration. Be careful with the amount of alcohol you drink when on doxazosin as alcohol may increase the risk of becoming dizzy or lightheaded.
• Doxazosin is usually started at a low dosage, which is increased slowly. If you discontinue doxasozin for several days, you may need to start it again at a lower dosage and slowly titrate it up. Seek your doctor's advice.
• Good blood pressure control requires lifestyle changes to also be made, such as stopping smoking, reducing dietary sodium intake, and increasing levels of physical activity. In addition, blood sugars and lipids should be kept within normal limits and antithrombotic therapy should be considered for certain people.
• Many patients require more than one drug to achieve blood pressure targets.
• Doxazosin may interact with drugs used for erectile dysfunction (ED). Talk to your doctor first before taking any drugs for ED.
• If you need to have cataract surgery, tell your healthcare provider that you take doxazosin tablets.