Side Effects of Cardura (doxazosin)

Cardura (doxazosin) is an alpha-1 adrenergic blocker used to treat high blood pressure (hypertension) and symptoms of benign prostatic hyperplasia (BPH, a noncancerous enlargement of the prostate gland). 

Cardura prevents norepinephrine that is released by nerves from binding to alpha-1 receptors on smooth muscle surrounding blood vessels and in the prostate and bladder. By blocking the effect of norepinephrine, Cardura relaxes the smooth muscle. 

Relaxation of the smooth muscle surrounding blood vessels causes them to enlarge (dilate) and thereby reduces blood pressure. Relaxation of smooth muscle in the prostate and bladder improves the flow of urine and reduces the pain and discomfort characteristic of BPH. 

Common side effects of Cardura include

• dizziness,
• fatigue,
• headache,
• shortness of breath,
• diarrhea,
• abdominal pain,
• fluid retention (edema) and
• low blood pressure.

Cardura causes significant reduction in blood pressure after administration of the first dose. This reduction in blood pressure may be associated with dizziness and fainting, especially when rising from a sitting position. 

Serious side effects of Cardura include

• priapism (painful, prolonged penile erection),
• a reduction in white blood cells, and
• intraoperative floppy iris syndrome (IFIS) during cataract surgery. 

Drug interactions of Cardura include vardenafil or tadalafil because the combination may cause excessive blood pressure reduction. 

There are no adequate studies of Cardura in pregnant women. There are no adequate studies of Cardura in nursing mothers. Consult your doctor before breastfeeding. 

Common side effects of doxazosin include:

• dizziness,
• fatigue,
• headache,
• shortness of breath,
• diarrhea,
• abdominal pain,
• edema (fluid accumulation) and
• low blood pressure.

Doxazosin causes significant reduction in blood pressure after administration of the first dose (first dose effect). This reduction in blood pressure may be associated with dizziness and fainting, especially when rising from a sitting position. To avoid this, patients should rise slowly from a sitting position, start treatment with the 1 mg dose, and then doses should be adjusted upwards slowly.

Priapism (painful, prolonged penile erection) and a reduction in white blood cells have been associated with doxazosin.

More serious

Doxazosin can cause intraoperative floppy iris syndrome (IFIS) during cataract surgery. Patients should inform their eye surgeon that they are taking doxazosin.

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.

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.

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.

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

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;
• 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.

CYP 3A Inhibitors

• In vitro studies suggest that doxazosin is a substrate of CYP 3A4. Strong CYP3A inhibitors may increase exposure to doxazosin.
• Monitor blood pressure and for symptoms of hypotension when Cardura is used concomitantly with strong CYP3A inhibitors.

Phosphodiesterase-5 (PDE-5) inhibitors

• Concomitant administration of Cardura with a phosphodiesterase-5 (PDE-5) inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension.
• Monitor blood pressure and for symptoms of hypotension.