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 clinical practice.
The incidence of adverse reactions has been ascertained from 3 placebo-controlled clinical trials involving 1,608 men where daily doses of 10 and 15 mg alfuzosin were evaluated. In these 3 trials, 473 men received UROXATRAL (alfuzosin HCl) 10 mg extended-release tablets. In these trials, 4% of patients taking UROXATRAL (alfuzosin HCl) 10 mg extended-release tablets withdrew from the trial due to adverse reactions, compared with 3% in the placebo group.
Table 1 summarizes adverse reactions that occurred in ≥2% of patients receiving UROXATRAL, and at a higher incidence than that of the placebo group. In general, the adverse reactions seen in long-term use were similar in type and frequency to the events described below for the 3-month trials.
Table 1 : Adverse Reactions Occurring in ≥2% of UROXATRAL-Treated Patients and More Frequently than with Placebo in 3-Month Placebo-Controlled Clinical Trials
|Dizziness||19 (2.8%)||27 (5.7%)|
|Upper respiratory tract infection||4 (0.6%)||14 (3.0%)|
|Headache||12 (1.8%)||14 (3.0%)|
|Fatigue||12 (1.8%)||13 (2.7%)|
The following adverse reactions, reported by between 1% and 2% of patients receiving UROXATRAL and occurring more frequently than with placebo, are listed alphabetically by body system and by decreasing frequency within body system:
Body as a whole: pain
Gastrointestinal system: abdominal pain, dyspepsia, constipation, nausea
Reproductive system: impotence
Respiratory system: bronchitis, sinusitis, pharyngitis
Signs and Symptoms of Orthostasis in Clinical Trials: The adverse reactions related to orthostasis that occurred in the double-blind phase 3 trials with alfuzosin 10 mg are summarized in Table 2. Approximately 20% to 30% of patients in these trials were taking antihypertensive medication.
Table 2: Number (%) of Patients with Symptoms Possibly Associated with Orthostasis in 3-Month Placebo-Controlled Clinical Trials
|Dizziness||19 (2.8%)||27 (5.7%)|
|Hypotension or postural hypotension||0||2 (0.4%)|
Testing for blood pressure changes or orthostatic hypotension was conducted in three controlled studies. Decreased systolic blood pressure (≤90 mm Hg, with a decrease ≥20 mm Hg from baseline) was observed in none of the 674 placebo patients and 1 (0.2%) of the 469 UROXATRAL patients. Decreased diastolic blood pressure (≤50 mm Hg, with a decrease ≥15 mm Hg from baseline) was observed in 3 (0.4%) of the placebo patients and in 4 (0.9%) of the UROXATRAL patients. A positive orthostatic test (decrease in systolic blood pressure of ≥20 mm Hg upon standing from the supine position) was seen in 52 (7.7%) of placebo patients and in 31 (6.6%) of the UROXATRAL patients.
The following adverse reactions have been identified during post approval use of UROXATRAL. 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.
General disorders: edema
Cardiac disorders: tachycardia, chest pain, angina pectoris in patients with pre-existing coronary artery disease, atrial fibrillation
Gastrointestinal disorders: diarrhea
Hepatobiliary disorders: hepatocellular and cholestatic liver injury (including cases with jaundice leading to drug discontinuation)
Respiratory system disorders: rhinitis
Reproductive system disorders: priapism
Skin and subcutaneous tissue disorders: rash, pruritis, urticaria, angioedema, toxic epidermal necrolysis
Vascular disorders: flushing
Blood and lymphatic system disorders: thrombocytopenia
During cataract surgery, a variant of small pupil syndrome known as Intraoperative Floppy Iris Syndrome (IFIS) has been reported in some patients on or previously treated with alpha adrenergic antagonists [see WARNINGS AND PRECAUTIONS].