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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 3) are based on combined data from seven placebo-controlled trials involving once-daily administration of CARDURA in doses of 1–16 mg in hypertensives and 0.5–8 mg in normotensives. The adverse events when the incidence in the CARDURA group was at least 1% are summarized in Table 3. No significant difference in the incidence of adverse events compared to placebo was seen except for dizziness, fatigue, hypotension, edema, and dyspnea. Dizziness and dyspnea appeared to be dose-related.

TABLE 3 : ADVERSE REACTIONS DURING PLACEBO-CONTROLLED STUDIES BENIGN PROSTATIC HYPERPLASIA

Body System (N=665) (N=300)
BODY AS A WHOLE
  Back Pain 1.80% 2.00%
  Chest Pain 1.20% 0.70%
  Fatigue 8.0%* 1.70%
  Headache 9.90% 9.00%
  Influenza-like Symptoms 1.10% 1.00%
  Pain 2.00% 1.00%
CARDIOVASCULAR SYSTEM
  Hypotension 1.7%* 0.00%
  Palpitation 1.20% 0.30%
DIGESTIVE SYSTEM
  Abdominal Pain 2.40% 2.00%
  Diarrhea 2.30% 2.00%
  Dyspepsia 1.70% 1.70%
  Nausea 1.50% 0.70%
METABOLIC AND NUTRITIONAL DISORDERS
  Edema 2.7%* 0.70%
NERVOUS SYSTEM
  Dizziness† 15.6%* 9.00%
  Mouth Dry 1.40% 0.30%
  Somnolence 3.00% 1.00%
RESPIRATORY SYSTEM
  Dyspnea 2.6%* 0.30%
  Respiratory Disorder 1.10% 0.70%
SPECIAL SENSES
  Vision Abnormal 1.40% 0.70%
UROGENITAL SYSTEM
  Impotence 1.10% 1.00%
  Urinary Tract Infection 1.40% 2.30%
SKIN & APPENDAGES
  Sweating Increased 1.10% 1.00%
PSYCHIATRIC DISORDERS
  Anxiety 1.10% 0.30%
  Insomnia 1.20% 0.30%
*p ≤ 0.05 for treatment differences
†Includes vertigo

In these placebo-controlled studies of 665 CARDURA patients treated for a mean of 85 days, additional adverse reactions have been reported. These are less than 1% and not distinguishable from those that occurred in the placebo group. Adverse reactions with an incidence of less than 1% but of clinical interest are (CARDURA vs. placebo): Cardiovascular System: angina pectoris (0.6% vs. 0.7%), postural hypotension (0.3% vs. 0.3%), syncope (0.5% vs. 0.0%), tachycardia (0.9% vs. 0.0%); Urogenital System: dysuria (0.5% vs. 1.3%); and Psychiatric Disorders: libido decreased (0.8% vs. 0.3%). The safety profile in patients treated for up to three years was similar to that in the placebo-controlled studies.

The majority of adverse experiences with CARDURA were mild.

Hypertension

CARDURA has been administered to approximately 4000 hypertensive patients, of whom 1679 were included in the hypertension clinical development program. In that program, minor adverse effects were frequent, but led to discontinuation of treatment in only 7% of patients. In placebo-controlled studies, adverse effects 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. The major reasons for discontinuation were postural effects (2%), edema, malaise/fatigue, and some heart rate disturbance, each about 0.7%.

In controlled hypertension clinical trials directly comparing CARDURA to placebo, there was no significant difference in the incidence of side effects, except for dizziness (including postural), weight gain, somnolence, and fatigue/malaise. 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 1–16 mg. Table 4 summarizes those adverse experiences (possibly/probably related) reported for patients in these hypertension studies where the prevalence rate in the doxazosin group was at least 0.5% or where the reaction is of particular interest.

TABLE 4 : ADVERSE REACTIONS DURING PLACEBO-CONTROLLED STUDIES

  HYPERTENSION DOXAZOSIN
(N=339)
PLACEBO
(N=336)
CARDIOVASCULAR SYSTEM
  Dizziness 19% 9%
  Vertigo 2% 1%
  Postural Hypotension 0.30% 0%
  Edema 4% 3%
  Palpitation 2% 3%
  Arrhythmia 1% 0%
  Hypotension 1% 0%
  Tachycardia 0.30% 1%
  Peripheral Ischemia 0.30% 0%
SKIN & APPENDAGES
  Rash 1% 1%
  Pruritus 1% 1%
MUSCULOSKELETAL SYSTEM
  Arthralgia/Arthritis 1% 0%
  Muscle Weakness 1% 0%
  Myalgia 1% 0%
CENTRAL & PERIPHERAL N.S.
  Headache 14% 16%
  Paresthesia 1% 1%
  Kinetic Disorders 1% 0%
  Ataxia 1% 0%
  Hypertonia 1% 0%
  Muscle Cramps 1% 0%
AUTONOMIC
  Mouth Dry 2% 2%
  Flushing 1% 0%
SPECIAL SENSES
  Vision Abnormal 2% 1%
  Conjunctivitis/Eye Pain 1% 1%
  Tinnitus 1% 0.30%
PSYCHIATRIC
  Somnolence 5% 1%
  Nervousness 2% 2%
  Depression 1% 1%
  Insomnia 1% 1%
  Sexual Dysfunction 2% 1%
CARDIOVASCULAR SYSTEM
  Dizziness 19% 9%
  Vertigo 2% 1%
  Postural Hypotension 0.30% 0%
  Edema 4% 3%
  Palpitation 2% 3%
  Arrhythmia 1% 0%
  Hypotension 1% 0%
  Tachycardia 0.30% 1%
  Peripheral Ischemia 0.30% 0%
SKIN & APPENDAGES  
  Rash 1% 1%
  Pruritus 1% 1%
MUSCULOSKELETAL SYSTEM
  Arthralgia/Arthritis 1% 0%
  Muscle Weakness 1% 0%
  Myalgia 1% 0%
CENTRAL & PERIPHERAL N.S.
  Headache 14% 16%
  Paresthesia 1% 1%
  Kinetic Disorders 1% 0%
  Ataxia 1% 0%
  Hypertonia 1% 0%
  Muscle Cramps 1% 0%
AUTONOMIC
  Mouth Dry 2% 2%
  Flushing 1% 0%
SPECIAL SENSES
  Vision Abnormal 2% 1%
  Conjunctivitis/Eye Pain 1% 1%
  Tinnitus 1% 0.30%
PSYCHIATRIC
  Somnolence 5% 1%
  Nervousness 2% 2%
  Depression 1% 1%
  Insomnia 1% 1%
  Sexual Dysfunction 2% 1%

Additional adverse reactions have been reported, but these are, in general, not distinguishable from symptoms that might have occurred in the absence of exposure to doxazosin. The following adverse reactions occurred with a frequency of between 0.5% and 1%: syncope, hypoesthesia, increased sweating, agitation, increased weight. The following additional adverse reactions were reported by < 0.5% of 3960 patients who received doxazosin in controlled or open, short-or long-term clinical studies, including international studies. Cardiovascular System: angina pectoris, myocardial infarction, cerebrovascular accident; Autonomic Nervous System: pallor; Metabolic: thirst, gout, hypokalemia; Hematopoietic: lymphadenopathy, purpura; Reproductive System: breast pain; Skin Disorders: alopecia, dry skin, eczema; Central Nervous System: paresis, tremor, twitching, confusion, migraine, impaired concentration; Psychiatric: paroniria, amnesia, emotional lability, abnormal thinking, depersonalization; Special Senses: parosmia, earache, taste perversion, photophobia, abnormal lacrimation; Gastrointestinal System: increased appetite, anorexia, fecal incontinence, gastroenteritis; Respiratory System: bronchospasm, sinusitis, coughing, pharyngitis; Urinary System: renal calculus; General Body System: hot flushes, back pain, infection, fever/rigors, decreased weight, influenza-like symptoms.

CARDURA has not been associated with any clinically significant changes in routine biochemical tests. No clinically relevant adverse effects were noted on serum potassium, serum glucose, uric acid, blood urea nitrogen, creatinine or liver function tests. CARDURA has been associated with decreases in white blood cell counts (see PRECAUTIONS, Leukopenia/Neutropenia).

In post-marketing experience, the following additional adverse reactions have been reported: Autonomic Nervous System: priapism; Central Nervous System: hypoesthesia; Endocrine System: gynecomastia; Gastrointestinal System: vomiting; General Body System: allergic reaction; Heart Rate/Rhythm: bradycardia; Hematopoietic: leukopenia, thrombocytopenia; Liver/Biliary System: hepatitis, hepatitis cholestatic; Respiratory System: bronchospasm aggravated; Skin Disorders: urticaria; Special Senses: Intraoperative Floppy Iris Syndrome (see PRECAUTIONS, Cataract Surgery); Urinary System: hematuria, micturition disorder, micturition frequency, nocturia.