Linked Life Data

Uroxatral (Tablet, Extended Release)

Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/3799

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PredicateObject
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Uroxatral (Tablet, Extended Release)
dailymed-instance:dosage
The recommended dosage is one 10 mg UROXATRAL (alfuzosin HCl extended-release tablets) tablet daily to be taken immediately after the same meal each day. The tablets should not be chewed or crushed.
dailymed-instance:descripti...
Each UROXATRAL (alfuzosin HCl extended-release tablets) tablet contains 10 mg alfuzosin hydrochloride as the active ingredient. Alfuzosin hydrochloride is a white to off-white crystalline powder that melts at approximately 240��C. It is freely soluble in water, sparingly soluble in alcohol, and practically insoluble in dichloromethane. Alfuzosin hydrochloride is (R,S)-N-[3-[(4-amino-6,7-dimethoxy-2-quinazolinyl) methylamino] propyl] tetrahydro-2-furancarboxamide hydrochloride. The empirical formula of alfuzosin hydrochloride is CHNO���HCl. The molecular weight of alfuzosin hydrochloride is 425.9. Its structural formula is: The tablet also contains the following inactive ingredients: colloidal silicon dioxide (NF), ethylcellulose (NF), hydrogenated castor oil (NF), hydroxypropyl methylcellulose (USP), magnesium stearate (NF), mannitol (USP), microcrystalline cellulose (NF), povidone (USP), and yellow ferric oxide (NF).
dailymed-instance:clinicalP...
The symptoms associated with benign prostatic hyperplasia (BPH) such as urinary frequency, nocturia, weak stream, hesitancy and incomplete emptying are related to two components, anatomical (static) and functional (dynamic). The static component is related to the prostate size. Prostate size alone does not correlate with symptom severity. The dynamic component is a function of the smooth muscle tone in the prostate and its capsule, the bladder neck, and the bladder base as well as the prostatic urethra. The smoothmuscle tone is regulated by alpha-adrenergic receptors. Alfuzosin exhibits selectivity for alpha-adrenergic receptors in the lower urinary tract. Blockade of these adrenoreceptors can cause smooth muscle in the bladder neck and prostate to relax, resulting in an improvement in urine flow and a reduction in symptoms of BPH. UROXATRAL (alfuzosin HCl extended-release) is a selective antagonist of post-synaptic alpha-adrenoreceptors, which are located in the prostate, bladder base, bladder neck, prostatic capsule, and prostatic urethra.<br/>Pharmacokinetics: The pharmacokinetics of UROXATRAL have been evaluated in adult healthy male volunteers after single and/or multiple administration with daily doses ranging from 7.5 mg to 30 mg, and in patients with BPH at doses from 7.5 mg to 15 mg.<br/>Absorption: The absolute bioavailability of UROXATRAL 10 mg tablets under fed conditions is 49%. Following multiple dosing of 10 mg UROXATRAL under fed conditions, the time to maximum concentration is 8 hours. Cand AUCare 13.6 (SD = 5.6) ng/mL and 194 (SD = 75) ng��h/mL, respectively. UROXATRAL exhibits linear kinetics following single and multiple dosing up to 30 mg. Steady-state plasma levels are reached with the second dose of UROXATRAL administration. Steady-state alfuzosin plasma concentrations are 1.2- to 1.6-fold higher than those observed after a single administration.<br/>Effect of Food: As illustrated in Figure 1, the extent of absorption is 50% lower under fasting conditions. Therefore, UROXATRAL should be taken immediately following a meal.<br/>Distribution: The volume of distribution following intravenous administration in healthy male middle-aged volunteers was 3.2 L/kg. Results of in vitro studies indicate that alfuzosin is moderately bound to human plasma proteins (82% to 90%), with linear binding over a wide concentration range (5 to 5,000 ng/mL).<br/>Metabolism: Alfuzosin undergoes extensive metabolism by the liver, with only 11% of the administered dose excreted unchanged in the urine. Alfuzosin is metabolized by three metabolic pathways: oxidation, O-demethylation, and N-dealkylation. The metabolites are not pharmacologically active. CYP3A4 is the principal hepatic enzyme isoform involved in its metabolism.<br/>Excretion and Elimination: Following oral administration ofC-labeled alfuzosin solution, the recovery of radioactivity after 7 days (expressed as a percentage of the administered dose) was 69% in feces and 24% in urine. Following oral administration of UROXATRAL 10 mg tablets, the apparent elimination half-life is 10 hours.<br/>Special Populations:<br/>Elderly: In a pharmacokinetic assessment during phase 3 clinical studies in patients with BPH, there was no relationship between peak plasma concentrations of alfuzosin and age. However, trough levels were positively correlated with age. The concentrations in subjects���75 years of age were approximately 35% greater than in those below 65 years of age.<br/>Patients with Renal Impairment: The Pharmacokinetic profiles of UROXATRAL 10 mg tablets in subjects with normal renal function (CL>80 mL/min), mild impairment (CL60 to 80 mL/min), moderate impairment (CL30 to 59 mL/min), and severe impairment (CL<30 mL/min) were compared. These clearances were calculated by the Cockcroft-Gault formula. Relative to subjects with normal renal function, the mean Cand AUC values were increased by approximately 50% in patients with mild, moderate, or severe renal impairment. (See PRECAUTIONS, Renal Insufficiency).<br/>Patients with Hepatic Insufficiency: In patients with moderate or severe hepatic insufficiency (Child-Pugh categories B and C), the plasma apparent clearance (CL/F) was reduced to approximately one-third to one-fourth that observed in healthy subjects. This reduction in clearance results in three to four-fold higher plasma concentrations of alfuzosin in these patients compared to healthy subjects. Therefore, UROXATRAL is contraindicated in patients with moderate to severe hepatic impairment . The pharmacokinetics of UROXATRAL have not been studied in patients with mild hepatic insufficiency. .<br/>Drug-Drug Interactions:<br/>Metabolic interactions: CYP3A4 is the principal hepatic enzyme isoform involved in the metabolism of alfuzosin. Potent CYP3A4 inhibitors Repeated administration of 400 mg of ketoconazole, a potent inhibitor of CYP3A4, increased alfuzosin C2.3-fold and AUC3.2-fold following a single 10 mg dose of alfuzosin. Therefore, UROXATRAL should not be co-administered with potent inhibitors of CYP3A4 because exposure is increased, (e.g., ketoconazole, itraconazole, or ritonavir). . Moderate CYP3A4 inhibitors<br/>Other interactions:<br/>Electrophysiology: The effect of 10 mg and 40 mg alfuzosin on QT interval was evaluated in a double-blind, randomized, placebo and active-controlled (moxifloxacin 400 mg), 4-way crossover single dose study in 45 healthy white male subjects aged 19 to 45 years. The QT interval was measured at the time of peak alfuzosin plasma concentrations. The 40 mg dose of alfuzosin was chosen because this dose achieves higher blood levels than those achieved with the co-administration of UROXATRAL and ketoconazole 400 mg. Table 1 summarizes the effect on uncorrected QT and mean corrected QT interval (QTc) with different methods of correction (Fridericia, population-specific, and subject-specific correction methods) at the timeof peak alfuzosin plasma concentrations. No single one of these correction methodologies is known to be more valid. The mean change of heart rate associated with a 10 mg dose of alfuzosin in this study was 5.2 beats/minute and 5.8 beats/minute with 40 mg alfuzosin. The change in heart rate with moxifloxacin was 2.8 beats/minute. The QT effect appeared greater for 40 mg compared to 10 mg alfuzosin. The effect of the highest alfuzosin dose (four times the therapeutic dose) studied did not appear as large as that of the active control moxifloxacin at its therapeutic dose. This study, however, was not designed to make direct statistical comparisons between the drugs or the dose levels. There has been no signal of Torsade de Pointes in the extensive post-marketing experience with alfuzosin outside the United States. A separate post-marketing QT study evaluated the effect of the co-administration of 10 mg alfuzosin with a drug of similar QT effect size. In this study, the mean placebo-substracted QTcF increase of alfuzosin 10 mg alone was 1.9 msec (upperbound 95% CI, 5.5 msec). The concomitant administration of the two drugs showed an increased QT effect when compared with either drug alone. This QTcF increase [5.9 msec (UB 95% CI, 9.4 msec)] was not more than additive. Although this study was not designed to make direct statistical comparisons between drugs, the QT increase with both drugs given together appeared to be lower than the QTcF increase seen with the positive control moxifloxacin 400 mg [10.2 msec (UB 95% CI, 13.8 msec)]. The clinical impact of these QTc changes is unknown.<br/>Clinical Studies: Three randomized placebo-controlled, double-blind, parallel-arm, 12-week studies were conducted with the 10 mg daily dose of alfuzosin. In these three studies, 1,608 patients [mean age 64.2 years, range 49-92 years; Caucasian (96.1%), Black (1.6%), Asian (1.1%), Other (1.2%) were randomized and 473 patients received UROXATRAL 10 mg daily. Table 1 provides the results of the three studies that evaluated the 10 mg dose. There were two primary efficacy variables in these three studies. The International Prostate Symptom Score (IPSS, or AUA Symptom Score) consists of seven questions that assess the severity of both irritative (frequency, urgency, nocturia) and obstructive (incomplete emptying, stopping and starting, weak stream, and pushing or straining) symptoms, with possible scores ranging from 0 to 35. The second efficacy variable was peak urinary flow rate. The peak flow rate was measured just prior to the next dose in study 2 and on average at 16 hours post-dosing in studies 1 and 3. There was a statistically significant reduction from baseline to last assessment (Week 12) in the IPSS versus placebo in all three studies, indicating a reduction in symptom severity (Table 2 and Figures 2, 3, and 4). Peak urinary flow rate was increased statistically significantly from baseline to last assessment (Week 12) versus placebo in studies 1 and 2 (Table 3 and Figures 5, 6, and 7). Mean total IPSS decreased at the first scheduled observation at Day 28 and mean peak flow rate increased starting at the first scheduled observation at Day 14 in studies 2 and 3 and Day 28 in study 1.
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dailymed-instance:supply
UROXATRAL (alfuzosin HCl extended-release tablets) 10 mg is available as a round, three-layer tablet: one white layer between two yellow layers, debossed with X10. UROXATRAL is supplied as follows: Store at 25��C (77��F); excursions permitted to 15��to 30��C (59��to 86��F) [see USP Controlled Room Temperature]. Protect from light and moisture. Keep UROXATRAL out of reach of children.
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dailymed-instance:overdosag...
Should overdose of UROXATRAL (alfuzosin HCl extended-release tablets) lead to hypotension, support of the cardiovascular system is of first importance. Restoration of blood pressure and normalization of heart rate may be accomplished by keeping the patient in the supine position. If this measure is inadequate, then the administration of intravenous fluids should be considered. If necessary, vasopressors should then be used, and the renal function should be monitored and supported as needed. Alfuzosin is 82% to 90% proteinbound; therefore, dialysis may not be of benefit.
dailymed-instance:genericMe...
alfuzosin hydrochloride
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Uroxatral (Tablet, Extended Release)
dailymed-instance:adverseRe...
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. 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. 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.<br/>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 .
dailymed-instance:indicatio...
UROXATRAL (alfuzosin HCl extended-release tablets) is indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia. UROXATRAL is not indicated for the treatment of hypertension.
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dailymed-instance:name
Uroxatral