WARNINGS AND PRECAUTIONS
Postural hypotension with or without symptoms (e.g., dizziness) may develop within a few hours following administration of UROXATRAL. As with other alpha adrenergic antagonists, there is a potential for syncope. Patients should be warned of the possible occurrence of such events and should avoid situations where injury could result should syncope occur. There may be an increased risk of hypotension/postural hypotension and syncope when taking UROXATRAL concomitantly with anti-hypertensive medication and nitrates. Care should be taken when UROXATRAL is administered to patients with symptomatic hypotension or patients who have had a hypotensive response to other medications.
Patients with Renal Impairment
Caution should be exercised when UROXATRAL is administered in patients with severe renal impairment (creatinine clearance < 30 mL/min) [see Use in Specific Populations and Clinical Pharmacology].
Patients with Hepatic Impairment
UROXATRAL is contraindicated for use in patients with moderate or severe hepatic impairment [see Contraindications (4), Use in Specific Populations and Clinical Pharmacology]. Although the pharmacokinetics of UROXATRAL have not been studied in patients with mild hepatic impairment, caution should be exercised when UROXATRAL is administered to such patients [see Use in Specific Populations and Clinical Pharmacology].
Potent CYP3A4 Inhibitors: UROXATRAL is contraindicated for use with potent CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, ritonavir) since alfuzosin blood levels are increased [see Contraindications (4), Drug Interactions and Clinical Pharmacology].
Other alpha adrenergic antagonists: UROXATRAL is an alpha adrenergic antagonist and should not be used in combination with other alpha adrenergic antagonist [see Drug Interactions].
Phosphodiesterase-5 (PDE5) Inhibitors: PDE5-inhibitors are also vasodilators. Caution is advised for concomitant use of PDE5-inhibitors and UROXATRAL, as this combination can potentially cause symptomatic hypotension [see Drug Interactions].
Carcinoma of the prostate and benign prostatic hyperplasia (BPH) cause many of the same symptoms. These two diseases frequently coexist. Therefore, patients thought to have BPH should be examined to rule out the presence of carcinoma of the prostate prior to starting treatment with UROXATRAL.
Intraoperative Floppy Iris Syndrome (IFIS)
IFIS has been observed during cataract surgery in some patients on or previously treated with alpha adrenergic antagonists. This variant of small pupil syndrome is characterized by the combination of a flaccid iris that billows in response to intraoperative irrigation currents, progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs, and potential prolapse of the iris toward the phacoemulsification incisions. The patient's ophthalmologist should be prepared for possible modifications to their surgical technique, such as the utilization of iris hooks, iris dilator rings, or viscoelastic substances.
There does not appear to be a benefit of stopping alpha adrenergic antagonist therapy prior to cataract surgery.
Rarely (probably less than 1 in 50,000), alfuzosin, like other alpha adrenergic antagonists, has been associated with priapism (persistent painful penile erection unrelated to sexual activity). Because this condition can lead to permanent impotence if not properly treated, patients should be advised about the seriousness of the condition [see Adverse Reactions and Patient Counseling Information [17.3]).
If symptoms of angina pectoris should appear or worsen, UROXATRAL should be discontinued.
Patients with Congenital or Acquired QT Prolongation
Use with caution in patients with acquired or congenital QT prolongation or who are taking medications that prolong the QT interval [see Clinical Pharmacology].
USE IN SPECIFIC POPULATIONS
Pregnancy Category B. UROXATRAL is not indicated for use in women, and there are no studies of alfuzosin in pregnant women
Alfuzosin was not teratogenic, embryotoxic or fetotoxic in rats at plasma exposure levels (based on AUC of unbound drug) up to 1200 times (maternal oral dose of 250 mg/kg/day) the maximum recommended human dose (MRHD) of 10 mg. In rabbits administered up to 3 times the MRHD (based on body surface area) (maternal oral dose of 100 mg/kg/day) no embryofetal toxicity or teratogenicity was observed. Gestation was slightly prolonged in rats at exposure levels (based on AUC of unbound drug) approximately 12 times (greater than 5 mg/kg/day oral maternal dose) the MRHD, but difficulties with parturition were not observed.
UROXATRAL is not indicated for use in the pediatric population.
Efficacy of alfuzosin hydrochloride was not demonstrated in a randomized, double-blind, placebo-controlled, efficacy and safety trial conducted in 172 patients ages 2 to 16 years with elevated detrusor leak point pressure (LPP≥40 cm H2O) of neurologic origin treated with alfuzosin hydrochloride using pediatric formulations. The trial included a 12-week efficacy phase followed by a 40-week safety extension period. No statistically significant difference in the proportion of patients achieving a detrusor leak point pressure of <40 cmH20 was observed between the alfuzosin and placebo groups.
During the placebo-controlled trial, the adverse reactions reported in ≥2% of patients treated with alfuzosin and at a higher incidence than in the placebo group were: pyrexia, headache, respiratory tract infection, cough, epistaxis and diarrhea. The adverse reactions reported for the whole 12-month trial period, which included the open-label extension, were similar in type and frequency to the reactions observed during the 12-week period.
Alfuzosin hydrochloride was not studied in patients below the age of 2.
Of the total number of subjects in clinical studies of UROXATRAL, 48% were 65 years of age and over, whereas 11% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, but greater sensitivity of some older individuals cannot be ruled out [see Clinical Pharmacology]
Systemic exposure was increased by approximately 50% in pharmacokinetic studies of patients with mild, moderate, and severe renal impairment [see Clinical Pharmacology]. In phase 3 studies, the safety profile of patients with mild (n=172) or moderate (n=56) renal impairment was similar to the patients with normal renal function in those studies. Safety data are available in only a limited number of patients (n=6) with creatinine clearance below 30 mL/min; therefore, caution should be exercised when UROXATRAL is administered in patients with severe renal impairment [see Warnings and Precautions].
The pharmacokinetics of UROXATRAL have not been studied in patients with mild hepatic impairment. UROXATRAL is contraindicated for use in patients with moderate or severe hepatic impairment [see Contraindications (4), Warnings and Precautions and Clinical Pharmacology].