アルフゾシン

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.

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).

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).

/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.

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

alfuzosin

DILI Positive

Oral

DOI:10.1016/j.drudis.2019.09.022

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).

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).

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ There was no evidence of a drug-related increase in the incidence of tumors in mice following dietary administration of 100 mg/kg/day alfuzosin for 98 weeks in females and males, respectively. The highest dose tested in female mice may not have constituted a maximally tolerated dose. Likewise, there was no evidence of a drug-related increase in the incidence of tumors in rats following dietary administration of 100 mg/kg/day alfuzosin for 104 weeks in females and males, respectively. /Alfuzosin Hydrochloride/

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ There was no evidence of reproductive organ toxicity when male rats were given alfuzosin at daily oral (gavage) doses of up to 250 mg/kg/day for 26 weeks ... No impairment of fertility was observed following oral (gavage) administration to male rats at doses of up to 125 mg/kg/day for 70 days. Estrous cycling was inhibited in rats and dogs at doses of 25 mg/kg and 20 mg/kg, respectively ... although this did not result in impaired fertility in rats. /Alfuzosin Hydrochloride/

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ There was no evidence of teratogenicity or embryotoxicity in rats at maternal (oral gavage) doses up to 250 mg/kg/day ... In rabbits, up to the dose of 100 mg/kg/day ... given orally (via gavage), no evidence of fetal toxicity or teratogenicity was seen. /Alfuzosin Hydrochloride/

/LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Gestation was slightly prolonged in rats with a maternal dose >5 mg/kg/day (oral gavage) ... but there were no difficulties with parturition. /Alfuzosin Hydrochloride/

/GENOTOXICITY/ Alfuzosin showed no evidence of mutagenic effect in the Ames and mouse lymphoma assays, and was free of any clastogenic effects in the Chinese hamster ovary cell and in vivo mouse micronucleus assays. Alfuzosin treatment did not induce DNA repair in a human cell line.

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).

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)

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/

Medication: antihypertensive

Use (kg; approx.) in Germany (2009): >250

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/