Doxazosin Mesylate

Cardura, Cardura XL

The recommended dose of doxazosin for hypertension is 1-16 mg daily. The recommended dose for benign prostatic hyperplasia is 1-8 mg daily.

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.

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.

Table 1: Adverse Reactions Occurring more than 1% More Frequently in BPH Patients Treated with Cardura Versus Placebo

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

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.

Table 2: Adverse Reactions Occurring more than 1% More Frequently in Hypertensive Patients Treated with Cardura versus Placebo

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

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];

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.

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

Doxazosin may cause dizziness or fainting, especially when you first start taking it or when you start taking it again. Be careful if you drive or do anything that requires you to be alert. Avoid standing for long periods of time or becoming overheated during exercise and in hot weather. Avoid getting up too fast from a sitting or lying position, or you may feel dizzy.

If you stop taking doxazosin for any reason, call your doctor before you start taking it again. You may need a dose adjustment.

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.

Tell your doctor about all other medications you use, especially other blood pressure medications including diuretics (water pills).

• Enlarged Prostate (BPH, Benign Prostatic Hyperplasia)

No formal drug interaction studies to date, but no interactions observed in patients receiving various agents concomitantly during clinical trials.1 (See Specific Drugs and Laboratory Tests.)

Antihypertensive Agents

Potential pharmacodynamic interaction (additive hypotensive effects; initiate additional antihypertensive agents with caution).1

Drugs Affecting Hepatic Metabolism

Potential pharmacokinetic interaction; use concomitantly with caution.1

Protein-bound Drugs

Potential pharmacokinetic interaction (displacement of doxazosin or other protein-bound drug); no information available to date on effect of other highly protein-bound drugs on doxazosin binding.1 Doxazosin has no effect on protein binding of certain drugs in vitro.1 (See Specific Drugs and Laboratory Tests.)

Specific Drugs and Laboratory Tests

Storage

Oral

<30°C.1

• Reduces peripheral vascular resistance and BP as a result of vasodilating effects; produces both arterial and venous dilation.1 2 3 4 6

• Binds to α-adrenergic receptors on the prostate capsule, prostate adenoma, and the bladder trigone, resulting in decreased urinary outflow resistance in men.1 5

• May improve to limited extent the serum lipid profile (e.g., small increases in HDL and HDL/total cholesterol ratio; small decreases in LDL, total cholesterol, and triglyceride concentrations).1 2 3 Can decrease blood glucose and serum insulin concentrations.2