Cardura

This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

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, there are no specific foods that you must exclude from your diet when receiving this medication.

Before taking Cardura, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to Cardura or any inactive ingredient in Cardura
• have or have ever had prostate cancer
• have or have ever had liver disease
• are pregnant or breastfeeding

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Take Cardura exactly as prescribed. Follow the directions on your prescription label carefully.

The recommended starting dose of Cardura is 1 mg. The dose is gradually increased to manage side effects. The maximum dose for enlarged prostate is 8 mg per day. The maximum dose for the treatment of hypertension is 16 mg per day.

You should not use this medicine if you are allergic to doxazosin or similar medicines such as alfuzosin (Uroxatral), prazosin (Minipress), silodosin (Rapaflo), tamsulosin (Flomax), or terazosin (Hytrin).

To make sure doxazosin is safe for you, tell your doctor if you have:

• a blockage in your digestive tract (stomach or intestines);

• severe constipation;

• liver disease; or

• low blood pressure.

Doxazosin can affect your pupils during cataract surgery. Tell your eye surgeon ahead of time that you are using this medication. Do not stop using doxazosin before surgery unless your surgeon tells you to.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether doxazosin passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• an antibiotic;

• an antidepressant;

• medicine to treat HIV or AIDS; or

• sildenafil (Viagra) or other erectile dysfunction medicines.

This list is not complete. Other drugs may interact with doxazosin, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Postsynaptic α1-adrenergic blocking agent; quinazoline derivative.1 2 3 4 5 6

Contraindications

• Known hypersensitivity to doxazosin, quinazolines (e.g., prazosin, terazosin), or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Marked hypotension, especially in the upright position, can occur; may be accompanied by syncope and other postural effects (e.g., dizziness, lightheadedness, vertigo).1

Postural effects are most common after initial dose but may also occur when dosage is increased or when therapy is resumed after an interruption exceeding a few days.1

To decrease risk of excessive hypotension and syncope, initiate therapy at a low dosage (i.e., 1 mg daily) and titrate slowly; initiate concomitant antihypertensive agents with caution.1

If syncope or hypotension occurs, place patient in a recumbent position and institute supportive therapy as necessary; a transient hypotensive response is not a contraindication to further doses.1

Use with particular caution in patients in occupations in which orthostatic hypotension could be dangerous.1

Priapism reported rarely; may lead to permanent impotence if not treated promptly.1

General Precautions

Exclude possibility of prostate cancer before initiation of therapy for BPH.1

Possible decreases in leukocyte and neutrophil counts in patients receiving α1-adrenergic blocking agents, including doxazosin.1

Specific Populations

Category C.1

Distributed into milk in rats; not known whether distributed into human milk.1 Caution if used in nursing women.1

Safety and efficacy not established in children <18 years of age.1

Geriatric patients may be particularly susceptible to postural effects.7

BPH: Safety and efficacy were similar in those ≥65 years of age compared with younger patients.1

Hypertension: Clinical studies did not include sufficient numbers of patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults; other clinical experience has not revealed age-related differences in response.1 Select dosage with caution.1 (See Geriatric Patients under Dosage and Administration.)

Use with caution in patients with hepatic impairment and those who are receiving other agents known to influence hepatic metabolism.1 (See Interactions.)

Common Adverse Effects

Dizziness, headache, drowsiness, fatigue, edema, nausea, dyspnea, somnolence, abdominal pain, diarrhea.1 2 3 4 6

Storage

Oral

<30°C.1

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• Dizziness or lightheadedness

• Blurred vision
• confusion
• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position
• fainting (sudden)
• fast and pounding heartbeat
• irregular heartbeat
• shortness of breath
• sweating
• swelling of feet or lower legs

• Painful or prolonged erection of the penis (called priapism), although extremely rare, must have immediate medical attention. If painful or prolonged erection occurs, call your doctor or go to an emergency room as soon as possible

• Abdominal or stomach pain
• area rash
• black, tarry stools
• bleeding gums
• blood in urine or stools
• chest pain or discomfort
• chills
• clay-colored stools
• cough
• dark urine
• diarrhea
• difficulty breathing
• difficult, burning, or painful urination
• fever
• general tiredness and weakness
• headache, sudden and severe
• inability to speak
• itching
• lab results that show problems with liver
• light-colored stools
• loss of appetite
• noisy breathing
• pain or discomfort in arms, jaw, back or neck
• pinpoint red or purple spots on skin
• rash
• seizures
• slow or irregular heartbeat
• slurred speech
• sore throat
• sores, ulcers, or white spots on lips or in mouth
• swollen glands
• temporary blindness
• tightness in chest
• unpleasant breath odor
• unusual bleeding or bruising
• upper right abdominal pain
• vomiting
• vomiting of blood
• weakness in arm and/or leg on one side of the body, sudden and severe
• wheezing
• yellow eyes and skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Headache
• lack or loss of strength
• unusual tiredness or weakness

• Acid or sour stomach
• back pain
• belching
• bladder pain
• cloudy urine
• difficulty in moving
• frequent urge to urinate
• heartburn
• indigestion
• joint pain
• lower back or side pain
• muscle aching, cramping, or weakness
• muscle pains or stiffness
• nausea
• nervousness, restlessness, unusual irritability
• runny nose
• sleepiness or drowsiness
• sneezing
• sore throat
• stomach discomfort, upset or pain
• swollen joints

• Anxiety
• burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feeling
• change in frequency or urination
• dry mouth
• feeling of warmth
• frequent urination
• general feeling of discomfort or illness
• hair loss
• hives or welts
• hyperventilation
• increased urge to urinate during the night
• increased volume of pale dilute urine
• loss of appetite
• painful urination
• redness of skin
• redness of the face, neck, arms and occasionally upper chest
• shaking
• swelling of the breasts or breast soreness in both females and males
• thinning of hair
• trouble in holding or releasing urine
• trouble sleeping
• waking to urinate at night
• weight loss

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Tablets (scored): 1 mg (white), 2 mg (yellow), 4 mg (orange) or 8 mg (green).

Clinical Trials Experience

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 practice.

Benign Prostatic Hyperplasia (BPH)

The incidence of adverse events has been ascertained from worldwide clinical trials in 965 BPH patients. The incidence rates presented below (Table 2) are based on combined data from seven placebo-controlled trials involving once-daily administration of Cardura in doses of 1 to 16 mg in hypertensives and 0.5 to 8 mg in normotensives. Adverse reactions occurring more than 1% more frequently in BPH patients treated with Cardura vs placebo are summarized in Table 1.

Other adverse reactions occurring less than 1% more frequently in BPH patients treated with Cardura vs placebo but plausibly related to Cardura include: palpitations.

Hypertension

Cardura has been administered to approximately 4000 hypertensive patients in clinical trials, of whom 1679 were included in the hypertension clinical development program. In placebo-controlled studies, adverse events occurred in 49% and 40% of patients in the doxazosin and placebo groups, respectively, and led to discontinuation in 2% of patients in each group.

Adverse reactions occurring more than 1% more frequently in hypertensive patients treated with Cardura vs placebo are summarized in Table 1. . Postural effects and edema appeared to be dose-related. The prevalence rates presented below are based on combined data from placebo-controlled studies involving once-daily administration of doxazosin at doses ranging from 1 to 16 mg.

Other adverse reactions occurring less than 1% more frequently in hypertensive patients treated with Cardura vs placebo but plausibly related to Cardura use include vertigo, hypotension, hot flushes, epistaxis and oedema.

Cardura has been associated with decreases in white blood cell counts

Laboratory changes observed in clinical studies

Leukopenia/Neutropenia: Decreases in mean white blood cell (WBC) and mean neutrophil count were observed in controlled clinical trials of hypertensive patients receiving Cardura. In cases where follow-up was available, WBC and neutrophil counts returned to normal after discontinuation of Cardura. No patients became symptomatic as a result of the low WBC or neutrophil counts.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Cardura. 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.

In post-marketing experience, the following additional adverse reactions have been reported:
Blood and Lymphatic System Disorders: leukopenia, thrombocytopenia;
Immune System Disorders: allergic reaction;
Nervous System Disorders: hypoesthesia;
Eye Disorders: Intraoperative Floppy Iris Syndrome [see Warnings and precautions (5.4)];
Cardiac Disorders: bradycardia;
Respiratory, Thoracic and Mediastinal Disorders: bronchospasm aggravated;
Gastrointestinal Disorders: vomiting;
Hepatobiliary Disorders: cholestasis, hepatitis cholestatic;
Skin and Subcutaneous Tissue Disorders: urticaria;
Musculoskeletal and Connective Tissue Disorders: muscle cramps, muscle weakness;
Renal and Urinary Disorders: hematuria, micturition disorder, micturition frequency, nocturia;
Reproductive System and Breast Disorders: gynecomastia, priapism.

Benign Prostatic Hyperplasia (BPH)

The efficacy of Cardura was evaluated extensively in over 900 patients with BPH in double-blind, placebo-controlled trials. Cardura treatment was superior to placebo in improving patient symptoms and urinary flow rate. Significant relief with Cardura was seen as early as one week into the treatment regimen, with Cardura-treated patients (N=173) showing a significant (p<0.01) increase in maximum flow rate of 0.8 mL/sec compared to a decrease of 0.5 mL/sec in the placebo group (N=41). In long-term studies, improvement was maintained for up to 2 years of treatment. In 66–71% of patients, improvements above baseline were seen in both symptoms and maximum urinary flow rate.

In three placebo-controlled studies of 14–16 weeks' duration, obstructive symptoms (hesitation, intermittency, dribbling, weak urinary stream, incomplete emptying of the bladder) and irritative symptoms (nocturia, daytime frequency, urgency, burning) of BPH were evaluated at each visit by patient-assessed symptom questionnaires. The bothersomeness of symptoms was measured with a modified Boyarsky questionnaire. Symptom severity/frequency was assessed using a modified Boyarsky questionnaire or an AUA-based questionnaire. Uroflowmetric evaluations were performed at times of peak (2–6 hours post-dose) and/or trough (24 hours post-dose) plasma concentrations of Cardura.

The results from the three placebo-controlled studies (N=609) showing significant efficacy with 4 mg and 8 mg doxazosin are summarized in Table 3. In all three studies, Cardura resulted in statistically significant relief of obstructive and irritative symptoms compared to placebo. Statistically significant improvements of 2.3–3.3 mL/sec in maximum flow rate were seen with Cardura in Studies 1 and 2, compared to 0.1–0.7 mL/sec with placebo.

In one fixed-dose study (Study 2), Cardura therapy (4 to 8 mg, once daily) resulted in a significant and sustained improvement in maximum urinary flow rate of 2.3–3.3 mL/sec (Table 3) compared to placebo (0.1 mL/sec). In this study, the only study in which weekly evaluations were made, significant improvement with Cardura vs. placebo was seen after one week. The proportion of patients who responded with a maximum flow rate improvement of ≥3 mL/sec was significantly larger with Cardura (34–42%) than placebo (13–17%). A significantly greater improvement was also seen in average flow rate with Cardura (1.6 mL/sec) than with placebo (0.2 mL/sec). The onset and time course of symptom relief and increased urinary flow from Study 1 are illustrated in Figure 1.

Hypertension

In a pooled analysis of placebo-controlled hypertension studies with about 300 hypertensive patients per treatment group, doxazosin, at doses of 1 to 16 mg given once daily, lowered blood pressure at 24 hours by about 10/8 mmHg compared to placebo in the standing position and about 9/5 mmHg in the supine position. Peak blood pressure effects (1–6 hours) were larger by about 50–75% (i.e., trough values were about 55–70% of peak effect), with the larger peak-trough differences seen in systolic pressures. There was no apparent difference in the blood pressure response of Caucasians and blacks or of patients above and below age 65. In the same patient population, patients receiving Cardura gained a mean of 0.6 kg compared to a mean loss of 0.1 kg for placebo patients.

Cardura (doxazosin mesylate) is available as scored tablets for oral administration. Each tablet contains doxazosin mesylate equivalent to 1 mg (white), 2 mg (yellow), 4 mg (orange) or 8 mg (green) of the active constituent, doxazosin.

Recommended Storage: Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature].

Pfizer
NDC 0049-2780-66

Cardura®
(doxazosin mesylate)
tablets

8 mg*

100 Tablets
Rx only

Tell your doctor about all your current medicines and any you start or stop using, especially:

• an antibiotic;

• an antidepressant;

• medicine to treat HIV or AIDS; or

• sildenafil (Viagra) or other erectile dysfunction medicines.

This list is not complete. Other drugs may interact with doxazosin, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.