The incidence of treatment-emergent adverse events has been ascertained from 3 placebo-controlled clinical trials involving 1,608 men in which 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 studies, 4% of patients taking UROXATRAL (alfuzosin HCl extended-release tablets) 10 mg tablets withdrew from the study due to adverse events, compared with 3% in the placebo group.
Table 4 summarizes the treatment-emergent adverse events that occurred in ≥2% of patients receiving UROXATRAL, and at an incidence numerically higher than that of the placebo group. In general, the adverse events seen in long-term use were similar in type and frequency to the events described below for the 3-month trials.
Table 4 — Treatment-Emergent Adverse Events Occurring in ≥2% of UROXATRAL-Treated Patients and More Frequently than with Placebo in 3-Month Placebo-Controlled Clinical Studies
|Adverse Event||Placebo (n=678)||UROXATRAL (n=473)|
|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 events, 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 Studies: The adverse events related to orthostasis that occurred in the double-blind phase 3 studies with alfuzosin 10 mg are summarized in Table 5. Approximately 20% to 30% of patients in these studies were taking antihypertensive medication.
Table 5 — Number (%) of Patients with Symptoms Possibly Associated with Orthostasis in 3-Month Placebo-Controlled Clinical Studies
|Symptoms||Placebo (n=678)||UROXATRAL (n=473)|
|Dizziness||19 (2.8%)||27 (5.7%)|
|Hypotension or postural hypotension||0||2 (0.4%)|
Multiple testing for blood pressure changes or orthostatic hypotension was conducted in the three controlled studies at each scheduled clinic visit (Days 14, 28, 56, and 84). Patients with a decrease in systolic blood pressure of >20 mm Hg after 2 minutes standing following being supine were excluded from the three trials. These tests were considered positive for blood pressure decrease if (1) supine systolic blood pressure was ≤90 mm Hg, with a decrease ≥20 mm Hg versus baseline, and/or (2) supine diastolic blood pressure was ≤50 mm Hg, with a decrease≥15 mm Hg versus baseline. The tests were considered positive for orthostatic hypotension if there was a decrease in systolic blood pressure of ≥20 mm Hg upon standing from the supine position during the orthostatic tests. According to these definitions, decreased systolic blood pressure was observed in none of the 674 placebo patients and 1 (0.2%) of the 469 UROXATRAL patients. Decreased diastolic blood pressure was observed in 3 (0.4%) of the placebo patients and in 4 (0.9%) of the UROXATRAL patients. A positive orthostatic test was seen in 52 (7.7%) of placebo patients and in 31 (6.6%) of the UROXATRAL patients.
No vital sign measurements were obtained following first dose administration in the phase 3 studies, except for a subset of patients in study 1 who had blood pressure measurements 12 to 16 hours after the first dose to assess the potential to produce orthostatic hypotension. None of these 35 UROXATRAL treated patients showed a positive test for systolic, diastolic or orthostatic blood pressure change.
Post-Marketing Adverse Event Reports
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.
General disorders: edema
Cardiac disorders: tachycardia, chest pain, angina pectoris in patients with pre-existing coronary artery disease
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
Vascular disorders: flushing
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-1 blockers (see PRECAUTIONS).