Alfuzosin

389.45

389.45

617-230-8

760065

DTXSID6048549

G04CA01|G - Genito urinary system and sex hormones

112

1.4

Solid

1.3±0.1 g/cm3

178-180 °C

1.621

2.82e-01 g/L

Store at 25 deg C (77deg F); excursions permitted to 15 deg to 30 deg C (59 deg to 86 deg F). Protect from light and moisture.

4.56X10-13 mm Hg at 25 deg C /Estimated/

Henry's Law constant = 9.5X10-20 atm-cu m/mol at 25 °C /Estimated/

pKa = 8.13|Mol wt: 425.92. Crystals from ethanol + ether, mp 225 °C, also reported earlier as 235 °C (dec). pKa 8.13 /Hydrochloride/

194.6 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]|193.9 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

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. /Hydrochloride/|Hydroxyl radical reaction rate constant = 2.42X10-14 cu cm/molc-sec at 25 °C /Estimated/

R20/21/22

S36/37

P260, P314, P501

H373

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies currently marketed prescription drug products, incl alfuzosin hydrochloride, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Alfuzosin Hydrochloride/

Wilde MI et al; Alfuzosin. A Review of its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Potential in Benign Prostatic Hyperplasia; Drugs 45 (3): 410-29 (1993)|Roehrborn CG; Alfuzosin: Overview of Pharmacokinetics, Safety, and Efficacy of a Clinically Uroselective alpha-Blocker; Urology 58 (6 Suppl 1): 55-63 (2001)

|Warning|H373 (100%): Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]|P260, P314, and P501|Aggregated GHS information provided by 4 companies from 1 notifications to the ECHA C&L Inventory.

Side effects are dizziness (due to postural hypotension), upper respiratory tract infection, headache, and fatigue.

Alfuzosin has been associated with a low rate of serum aminotransferase elevations (

Single administration of 100 mg atenolol with a single dose of 2.5 mg of an immediate release alfuzosin tablet in eight healthy young male volunteers increased alfuzosin Cmax and AUC values by 28% and 21%, respectively. Alfuzosin increased atenolol Cmax and AUC values by 26% and 14%, respectively. In this study, the combination of alfuzosin with atenolol caused significant reductions in mean blood pressure and in mean heart rate.|Repeated administration of 1 g/day cimetidine increased both alfuzosin Cmax and AUC values by 20%.|Repeated co-administration of 240 mg/day of diltiazem, a moderately-potent inhibitor of CYP3A4, with 7.5 mg/day (2.5 mg three times daily) alfuzosin increased the Cmax and AUC0-24 of alfuzosin 1.5- and 1.3-fold, respectively. Alfuzosin increased the Cmax and AUC0-12 of diltiazem 1.4- fold. Although no changes in blood pressure were observed in this study, diltiazem is an antihypertensive medication and the combination of Uroxatral and antihypertensive medications has the potential to cause hypotension in some patients. /Alfuzosin Hydrochloride/|Repeated administration of 400 mg of ketoconazole, a potent inhibitor of CYP3A4, increased alfuzosin Cmax 2.3-fold and AUClast 3.2-fold following a single 10 mg dose of alfuzosin. Uroxatral should not be co-administered with potent inhibitors of CYP3A4,(e.g., ketoconazole, itraconazole, or ritonavir). /Alfuzosin Hydrochloride/|For more Interactions (Complete) data for ALFUZOSIN (9 total), please visit the HSDB record page.

82%-90%

Alfuzosin's production and use as a antihypertensive(1) may result in its release to the environment through various waste streams.

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1,300(SRC), determined from a structure estimation method(2), indicates that alfuzosin is expected to have low mobility in soil(SRC). The pKa of alfuzosin is 8.13(3), indicating that this compound will primarily exist in the protonated form in the environment and cations generally adsorb to organic carbon and clay more strongly than their neutral counterparts(4). Volatilization of alfuzosin from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 9.5X10-20 atm-cu m/mole(5), using a fragment constant estimation method(5). Alfuzosin is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 4.6X10-13 mm Hg(SRC), determined from a fragment constant method(6). Biodegradation data were not available(SRC, 2004).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1,300(SRC), determined from a structure estimation method(2), indicates that alfuzosin is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon a an estimated Henry's Law constant of 9.5X10-20 atm-cu m/mole(4), developed using a fragment constant estimation and the natural catioinic state of the compound. The pKa of alfuzosin is 8.13(5), indicating that this compound will primarily exist in the protonated form in the environment and cations generally adsorb more strongly to suspended solids and sediment than their neutral counterparts(6). Hydrolysis is not expected to be an important environmental fate process since this compound lacks functional groups that may readily hydrolyze under environmental conditions. According to a classification scheme(7), an estimated BCF of 5(SRC), from an estimated log Kow of 1.86(8), and a regression-derived equation(9), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data were not available(SRC, 2004).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), alfuzosin, which has an estimated vapor pressure of 4.6X10-13 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase. Particulate-phase alfuzosin may be removed from the air by wet and dry deposition(SRC).

Particulate-phase alfuzosin may be removed from the air by wet and dry deposition(SRC). Alfuzosin is not expected to undergo hydrolysis this compound lacks functional groups that may readily hydrolyze under environmental conditions(1). By analogy to pyrimidine(2), alfuzosin is expected to absorb light in the environmental UV spectrum and may undergo direct photolysis in water or on soil(SRC).

An estimated BCF of 5 was calculated for alfuzosin(SRC), using an estimated log Kow of 1.86(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc for alfuzosin can be estimated to be 1,300(SRC). According to a classification scheme(2), this estimated Koc value suggests that alfuzosin is expected to have low mobility in soil. The pKa of alfuzosin is 8.13(3), indicating that this compound will primarily exist in the protonated form in the environment and cations generally adsorb more strongly to organic carbon and clay than their neutral counterparts(4).

The Henry's Law constant for alfuzosin is estimated as 9.47X10-20 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that alfuzosin is expected to be essentially nonvolatile. Alfuzosin is not expected to volatilize from dry soil surfaces(SRC) based upon a an estimated vapor pressure of 4.66X10-13 mm Hg(SRC), determined from a fragment constant method(3).

Occupational exposure to alfuzosin may occur through inhalation and dermal contact with this compound at workplaces where alfuzosin is produced or used. The general population may be exposed to alfuzosin via ingestion of pharmaceutical products containing alufozosin. (SRC)

For the reduction of urinary obstruction and relief of associated manifestations (eg. sensation of incomplete bladder emptying or straining, urgency, interrupted or weak stream) in patients with symptomatic beningn prostatic hyperplasia.|FDA Label

Alfuzosin is a nonselective alpha-1 adrenergic antagonist used in the therapy of benign prostatic hypertrophy. Alfuzosin is associated with a low rate of transient serum aminotransferase elevations and with rare instances of clinically apparent acute liver injury.

Benign Prostatic Hypertrophy Agents

Antihypertensive|Alfuzosin hydrochloride is used for the symptomatic management of benign prostatic hyperplasia (BPH, benign prostatic hypertrophy). Alfuzosin relieves moderate to severe irritative (e.g., frequency, urgency, nocturia) and obstructive (e.g., hesitancy, interrupted or weak stream, sensation of incomplete bladder emptying or straining) manifestations and improves urinary flow rates in a substantial proportion of patients.|Uroxatal is not indicated for the treatment of hypertension. /Alfuzosin Hydrochloride/

In a study of QT effect in 45 healthy males, the QT effect appeared less with alfuzosin 10 mg than with 40 mg, and the effect of alfuzosin 40 mg did not appear as large as that of the active control moxifloxacin at its therapeutic dose. This observation should be considered in clinical decisions to prescribe Uroxatral for patients with a known history of QT prolongation or patients who are taking medications known to prolong QT, although there has been no signal of Torsades de Pointe in the extensive postmarketing experience with alfuzosin outside the United States. There are no known PK/PD studies of the effects of other alpha blockers on cardiac repolarization. /Alfuzosin Hydrochloride/|Postural hypotension with or without symptoms (e.g., dizziness) may develop within a few hours following administration of Uroxatral (alfuzosin HCl extended-release tablets). As with other alpha-blockers, 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. Care should be taken when Uroxatral is administered to patients with symptomatic hypotension or patients who have had a hypotensive response to other medications.|Carcinoma of the prostate and benign prostatic hyperplasia cause many of the same symptoms. These two diseases frequently coexist. Therefore, patients thought to have benign prostatic hyperplasia should be examined prior to starting therapy with Uroxatral (alfuzosin HCl extended-release tablets) to rule out the presence of carcinoma of the prostate.|If symptoms of angina pectoris should newly appear or worsen, Uroxatral should be discontinued. /Extended Release Alfuzosin Hydrochloride/|For more Drug Warnings (Complete) data for ALFUZOSIN (16 total), please visit the HSDB record page.

Alfuzosin is a quinazoline-derivative alpha-adrenergic blocking agent used to treat hypertension and benign prostatic hyperplasia. Accordingly, alfuzosin is a selective inhibitor of the alpha(1) subtype of alpha adrenergic receptors. In the human prostate, alfuzosin antagonizes phenylephrine (alpha(1) agonist)-induced contractions, in vitro, and binds with high affinity to the alpha1a adrenoceptor, which is thought to be the predominant functional type in the prostate. Studies in normal human subjects have shown that alfuzosin competitively antagonized the pressor effects of phenylephrine (an alpha(1) agonist) and the systolic pressor effect of norepinephrine. The antihypertensive effect of alfuzosin results from a decrease in systemic vascular resistance and the parent compound alfuzosin is primarily responsible for the antihypertensive activity.

Drugs used in the treatment of urogenital conditions and diseases such as URINARY INCONTINENCE; PROSTATIC HYPERPLASIA; and ERECTILE DYSFUNCTION. (See all compounds classified as Urological Agents.)|Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS. (See all compounds classified as Adrenergic alpha-1 Receptor Antagonists.)

Absorption is 50% lower under fasting conditions|Following oral administration of 14C-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.|3.2 L/kg [healthy male middle-aged volunteers]|Following oral administration of (14)C-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. /Alfuzosin Hydrochloride/|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). /Alfuzosin Hydrochloride/|The extent of absorption is 50% lower under fasting conditions. Therefore, Uroxatral should be taken immediately following a meal. /Alfuzosin Hydrochloride/|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. Cmax and AUC0-24 are 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 by 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. /Extended Release Alfuzosin Hydrochloride/|For more Absorption, Distribution and Excretion (Complete) data for ALFUZOSIN (6 total), please visit the HSDB record page.

Hepatic. 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-demethylations, and N-dealkylation. The metabolites are not pharmacologically active. CYP3A4 is the principal hepatic enzyme isoform involved in its 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. /Alfuzosin Hydrochloride/

10 hours|Following oral administration of Uroxatral 10 mg tablets, the apparent elimination half-life is 10 hours. /Extended Release Alfuzosin Hydrochloride/

Alfuzosin is a non-subtype specific alpha(1)-adrenergic blocking agent that exhibits selectivity for alpha(1)-adrenergic receptors in the lower urinary tract. Inhibition of these adrenoreceptors leads to the relaxation of smooth muscle in the bladder neck and prostate, resulting in the improvement in urine flow and a reduction in symptoms in benign prostate hyperplasia. Alfuzosin also inhibits the vasoconstrictor effect of circulating and locally released catecholamines (epinephrine and norepinephrine), resulting in peripheral vasodilation.|Alfuzosin hydrochloride, a quinazoline-derivative alpha1-adrenergic blocking agent, is structurally and pharmacologically related to prazosin. Alfuzosin is a non-subtype-specific alpha1-adrenergic blocking agent that exhibits selectivity for alpha1-adrenergic receptors in the lower urinary tract (e.g., bladder base, bladder neck, prostate, prostatic capsule, prostatic urethra). Blockade of these adrenoreceptors can cause relaxation of smooth muscle in the bladder neck and prostate, resulting in improvement in urine flow and a reduction in symptoms of benign prostatic hyperplasia (BPH).

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% protein-bound; therefore, dialysis may not be of benefit.

/CASE REPORTS/ Drug-induced hepatic injury is a potential complication of virtually all drugs because the liver is central to the metabolic disposition of almost all drugs, although precise mechanisms often are unknown. We report a case of severe acute mixed hepatitis (cholestatic and hepatocellular), probably induced by alfuzosin. ... Viral causes, autoimmune hepatitis and biliary tree obstruction were excluded. After discontinuation of the drug, liver function test results returned to normal.|/CASE REPORTS/ An 80-year-old man was evaluated because of jaundice and pruritus. He was diagnosed as having Child-Pugh A chronic liver disease due to hepatitis B virus. Other etiologies of hepatitis were appropriately ruled out, and the hepatitis B was non-replicative. Therefore, elevated liver enzyme levels were ascribed to alfuzosin treatment. DISCUSSION: Although alfuzosin-related mixed-type hepatotoxicity has been previously reported, this is the first published case describing probable hepatocellular-type hepatotoxicity resulting from use of alfuzosin in a patient with underlying chronic liver disease. According to the Naranjo probability scale, alfuzosin was a probable cause of the hepatotoxicity. The mechanism of alfuzosin-induced liver damage is unknown. Several features, such as absence of predictable dose-dependent toxicity of alfuzosin in previous studies and absence of hypersensitivity manifestations in our case, are suggestive of a metabolic type of idiosyncratic toxicity.

Alfetim

Oral: Tablets, extended-release 10 mg Uroxatral (with povidone), (Sanofi-Synthelabo).|Uroxatral

Preparation: P.M.J. Manoury, DE 2904445; idem, US 4315007 (1979, 1982 both to Synthelabo)|Information available in 2004 indicated that Alfuzosin was used in the manufacture of pharmaceutical preparations in the following countries: Argentina, Romania|Information available in 2004 indicated that Alfuzosin hydrochloride was used in the manufacture of pharmaceutical preparations in the following countries: Algeria, Argentina, Austria, Belgium, Brazil, Canada, Chile, Colombia, Costa Rica, Czech Republic, Denmark, Dominican Republic, Ecuador, El Salvador, Finland, France, Germany, Greece, Guatemala, Honduras, Hong Kong, Hungary, Ireland, Israel, Italy, Luxembourg, Malaysia, Netherlands, Nicaragua, Norway, Panama, Poland, Portugal, Romania, Russian Federation, Singapore, South Africa, Spain, Sweden, Switzerland, Thailand, Turkey, United Kingdom, USA, Yugoslavia (1,2) /Alfuzosin hydrochloride/

HPLC determination in biological fluids.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients