6 ADVERSE REACTIONS Most common adverse reactions in clinical studies (incidence ≥2% and at a higher incidence than placebo): dizziness, upper respiratory tract infection, headache, fatigue. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 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 alfuzosin hydrochloride 10 mg extended-release tablets. In these trials, 4% of patients taking alfuzosin hydrochloride 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 alfuzosin hydrochloride extended-release tablets, 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 Alfuzosin Hydrochloride Extended-Release Tablets-Treated Patients and More Frequently than with Placebo in 3-Month Placebo-Controlled Clinical Trials Adverse Reaction Placebo (n=678) Alfuzosin hydrochloride (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 reactions, reported by between 1% and 2% of patients receiving alfuzosin hydrochloride 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 Symptoms Placebo (n=678) Alfuzosin hydrochloride (n=473) Dizziness 19 (2.8%) 27 (5.7%) Hypotension or postural hypotension 0 2 (0.4%) Syncope 0 1 (0.2%) 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 alfuzosin hydrochloride 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 alfuzosin hydrochloride 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 alfuzosin hydrochloride patients. 6.2 Post-Marketing Experience The following adverse reactions have been identified during post approval use of alfuzosin hydrochloride extended-release tablets. 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, vomiting 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 (5.6)].