Doxazosin mesylate

547.58

547.173706

1308068-626-2

759284

DTXSID5045598

29349990

175

2.88670

white powder

275-277°C

718°C at 760 mmHg

388ºC

Freely soluble in dimethylsulfoxide, soluble in dimethylformamide, slightly soluble in methanol, ethanol, and water (0.8 percent at 25 deg C), and very slighlty soluble in acetone and methylene chloride.

Desiccate at RT

203.3 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

Crystals, mp 289-290 °C /Hydrochloride/|Molecular weight: 451.47 /Doxazosin/

Ⅲ

2811

2

36/37/38

26-36/37-24/25

TK8044000

Xi

Protect from light

P273, P391, P501

H411

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

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

|Warning|H373 (86.6%): Causes damage to organs through prolonged or repeated exposure [Warning Specific target organ toxicity, repeated exposure]|P260, P273, P314, P391, and P501|Aggregated GHS information provided by 98 companies from 11 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H411 (100%): Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]|P273, P391, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

Doxazosin has been associated with a low rate of serum aminotransferase elevations that in controlled trials was no higher than with placebo therapy. These elevations were transient and did not require dose modification. No instances of clinically apparent acute liver injury due to doxazosin have been published in the literature, but reports of cholestatic hepatitis have been received by the sponsor. Among the alpha adrenergic receptor antagonists, the most frequently implicated agent in causing liver injury has been alfuzosin with only single, and not well documented cases linked to other alpha blockers. Thus, acute symptomatic liver injury due to doxazosin is quite rare, and severe hepatotoxicity must be exceeding rare, if it occurs at all.

Antihypertensive effects of doxazosin may be reduced when the medication is used concurrently with these agents; indomethacin, and possibly other /nonsteroidal anti-inflammatory drugs/ NSAIDs, may antagonize the antihypertensive effect by inhibiting renal prostaglandin synthesis and/or by causing sodium and fluid retention; the patient should be carefully monitored to confirm that the desired effect is being obtained. /Salt not specified/|Concurrent use may slightly increase the serum concentration of doxazosin; however, the clinical significance of this increase is not known. /Salt not specified/|Antihypertensive effects may be potentiated when these medications /other hypertension-producing medications/ are used concurrently with doxazosin; although some antihypertensive and/or diuretic combinations are frequently used to therapeutic advantage, dosage adjustments are necessary during concurrent use. /Salt not specified/|Antihypertensive effects of doxazosin may be reduced when it is used concurrently with these agents /sympathomimetics/; the patient should be carefully monitored to confirm that the desired effect is being obtained. /Salt not specified/|For more Interactions (Complete) data for DOXAZOSIN MESYLATE (9 total), please visit the HSDB record page.

Doxazosin is a nonselective alpha-1 adrenergic antagonist (alpha-blocker) used in the therapy of hypertension and benign prostatic hypertrophy. Doxazosin is associated with a low rate of transient serum aminotransferase elevations, but has not been linked to instances of clinically apparent acute liver injury.

Antihypertensive Agents

Doxazosin is indicated for the treatment of both the urinary outflow obstruction and the obstructive and irritative symptoms associated with benign prostatic hyperplasia (BPH). Obstructive symptoms are hesitation, intermittency, dribbling, weak urinary stream, and incomplete emptying of the bladder; while irritative symptoms include nocturia, daytime frequency, urgency, and burning. Doxaxosin may be used in nomotensive or hypertensive patients. In normotensive patients with BPH, doxazosin does not appear to significantly lower blood pressure. In hypertensive patients with BPH, both conditions are effectively treated with doxazosin. The long term effects of doxazosin on the incidence of acute urinary obstruction or other complications of BPH or on the need for surgery have not yet been determined. /Included in US product labeling/ /Salt not specified/|Doxazosin is indicated in the treatment of hypertension. /Included in US product labeling/ /Salt not specified/|Antihypertensive; in treatment of benign prostatic hypertrophy. /Salt not specified/|Evaluation of atherosclerosis is important in the treatment of hypertension. To evaluate the preventive effects of a small amount of alpha-blockade, arterial and endothelial dysfunction were measured by noninvasive tests, i.e., pulse wave velocity, acceleration plethysmography and strain-gauge plethysmography, in patients with essential hypertension. Fifteen patients (65+/-3 years old) with essential hypertension (WHO stage I or II) were analyzed in this study. We performed noninvasive evaluations to measure aortic stiffness and endothelial dysfunction, in addition to measuring blood pressure, cholesterol profile, and levels of cells adhesion molecules and nitric oxide before and 6 and 12 months after the start of doxazosin treatment (1.0 mg/day). Blood pressure and heart rate did not significantly change during treatment. The pulse wave velocity index was significantly reduced both at 6 (7.72+/-0.23 m/s; p<0.05) and 12 (7.34+/-0.26 m/s; p<0.05) months after the start of treatment compared to the pretreatment level that at baseline. There was also a significant improvement in b/a after 12 months (-0.46+/-0.04; p<0.05) and in d/a after 6 months (-0.38+/-0.03; p<0.05) and 12 months (-0.39+/-0.03; p=0.05) compared to the pretreatment values. Moreover, reactive hyperemia evaluated by strain-gauge plethysmography after 6 months (1.34+/-0.11; p<0.05) and 12 months (1.49+/-0.16; p<0.05) was significantly improved compared to that before treatment, and NOx was significantly increased after 12 months (89.7+/-15.7 micromol/l; p<0.005). These data suggest that a low dose of doxazosin may play an important role in improving arterial stiffness and endothelial dysfunction without changing cardiac hemodynamics. /Salt not specified/|For more Therapeutic Uses (Complete) data for DOXAZOSIN MESYLATE (18 total), please visit the HSDB record page.

Adverse effects occurring most frequently during doxazosin mesylate therapy for hypertension include dizziness, headache, drowsiness, lack of energy (eg, lethargy, fatigue), nausea, edema, and rhinitis. In patients receiving the drug for benign prostatic hyperplasia (BPH), the most frequent adverse effects are dizziness, headache, fatigue, edema, dyspnea, abdominal pain, and diarrhea. The frequency of adverse effects in controlled clinical trails generally has been lower in patients receiving doxazosin for BPH than in those receiving the drug for hypertension; however, dosages employed for this condition also generally have been lower than those for hypertension. /Salt not specified/|While adverse effects occur frequently in patients receiving the drug, most are mild to moderate in severity, and discontinuance of doxazosin secondary to adverse effects was required in only 7% of patients with hypertension during clinical trials. The principal reasons for discontinuance in patients with hypertension were postural effects in 2% of patients and edema, malaise/fatigue, and heart rate disturbance each in about 0.7% of patients. In controlled clinical trials in patients with hypertension, only dizziness (including postural effects), weight gain, somnolence, and malaise/fatigue occurred at rates significantly greater than those for placebo; postural effects and edema appeared to be dose related. Only dizziness, fatigue, hypotension, edema, and dyspnea occurred significantly more frequently with the drug than placebo in controlled clinical trials for BPH; dizziness and dyspnea appeared to be dose-related. /Salt not specified/|Besides dizziness ..., headache is the most common adverse nervous system effect associated with doxazosin therapy, occurring in about 14 or 10% of patients receiving the drug for hypertension or benign prostatic hyperplasia (BPH), respectively. Somnolence occurs in 5 or 3% of such patients, respectively, and pain in 2% of patients. Nervousness occurs in about 2% of patients receiving doxazosin for hypertension, and insomnia and anxiety occur in 1.2 and 1.1%, respectively, of those receiving the drug for BPH; insomnia occurs in 1% of hypertensive patients. Adverse nervous system effects occurring in 0.5-1% of patients include paresthesia, kinetic disorders, ataxia, hypertonia, hypoesthesia, agitation, depression, and decreased libido. Paresis, tremor, twitching, confusion, migraine, paroniria, amnesia, emotional lability, impaired concentration, abnormal thinking, and depresonalization have been reported in less than 0.5% of patients, but a causal relationship to the drug has not been established. /Salt not specified/|Nausea, diarrhea, and dry mouth are the most common adverse GI effects of doxazosin in hypertensive patients, occurring in 3, 2, and 2% of such patients, respectively, and abdominal pain, diarrhea, dyspepsia, nausea, and dry mouth are the most common in those with benign prostatic hyperplasia (BPH), occurring in 2.4, 2.3, 1.7, 1.5, and 1.4% of such patients, respectively; dyspepsia occurs in 1% of hypertensive patients. Constipation and flatulence occur in 1% of patients receiving the drug for hypertension. Increased appetite, anorexia, fecal incontinence, and gastroenteritis have been reported in less than 0.5% of hypertensive patients but not directly attributed to the drug. Vomiting has been reported during postmarketing experience with doxazosin. /Salt not specified/|For more Drug Warnings (Complete) data for DOXAZOSIN MESYLATE (12 total), please visit the HSDB record page.

Drugs that bind to and block the activation of ADRENERGIC ALPHA-1 RECEPTORS. (See all compounds classified as Adrenergic alpha-1 Receptor Antagonists.)|Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS. (See all compounds classified as Antihypertensive Agents.)

Most doxazosin metabolites are eliminated in the feces. /Salt not specified/|Well absorbed from gastrointestinal tract; bioavailability is about 65%. /Salt not specified/|Elimination: Fecal: Unchanged drug, about 5%; metabolites, 63 to 65%. Renal: 9%. /Salt not specified/

Metabolized extensively in the liver. Although several active and inactive metabolites have been identified (2-piperazinyl, 6' and 7'-hydroxy,6' and 7'-O-desmethyl, and 2-amino), there is no evidence that they are present in substantial amounts. /Salt not specified/

The half-life of doxazosin is approximately 20 hours ... /Salt not specified/|Elimination /half life/: 19 to 22 hours; does not appear to be significantly influenced by age or mild to moderate renal impairment. /Salt not specified/

Selective alpha1-adrenergic blocker related to prazosin, q.v. /Salt not specified/|Blocks postsynaptic alpha 1 receptors and cause vasodilation /Salt not specified/|Hypertension: Blockade of alpha1-adrenergic receptors by doxazosin results in peripheral vasodilation, which produces a fall in blood pressure because of decreased peripheral vascular resistance. Benign prostatic hyperplasia: Relaxation of smooth muscle in the bladder neck, prostate, and prostate capsule produced by alpha1-adrenergic blockade results in a reduction in urethral resistance and pressure, bladder outlet resistance, and urinary symptoms. /Salt not specified/|Previous studies have demonstrated that the alpha(1)-adrenergic receptor antagonist doxazosin (Dox) inhibits multiple mitogenic signaling pathways in human vascular smooth muscle cells. This broad antiproliferative activity of Dox occurs through a novel mechanism unrelated to its blocking the alpha(1)-adrenergic receptor. Flow cytometry demonstrated that Dox prevents mitogen-induced G(1)-->S progression of human coronary artery smooth muscle cells (CASMCs) in a dose-dependent manner, with a maximal reduction of S-phase transition by 88+/-10.5% in 20 ng/mL platelet-derived growth factor and 1 micromol/L insulin (P+I)-stimulated cells (P<0.01 for 10 micromol/L Dox versus P+I alone) and 52+/-18.7% for 10% FBS-induced mitogenesis (P<0.05 for 10 micromol/L Dox versus 10% FBS alone). Inhibition of G(1) exit by Dox was accompanied by a significant blockade of retinoblastoma protein (Rb) phospstimulated quiescent CASMCs to progress through G(1) and enter the S phase. E2F-mediated G(1) exit was not affected by Dox, suggesting that it targets events upstream from Rb hyperphosphorylation. Downregulation of the cyclin-dependent kinase inhibitory protein p27 is important for maximal activation of G(1) cyclin/cyclin-dependent kinase holoenzymes to overcome the cell cycle inhibitory activity of Rb. In Western blot analysis, p27 levels decreased after mitogenic stimulation (after P+I, 43+/-1.8% of quiescent cells [P<0.01 versus quiescent cells]; after 10% FBS, 55+/-7.7% of quiescent cells [P<0. 05 versus quiescent cells]), whereas the addition of Dox (10 micromol/L) markedly attenuated its downregulation (after P+I, 90+/-8.3% of quiescent cells [P<0.05 versus P+I alone]; after 10% FBS, 78+/-8.3% of quiescent cells [P<0.05 versus 10% FBS alone]). Furthermore, Dox inhibited cyclin A expression, an E2F regulated gene that is essential for cell cycle progression into the S phase. The present study demonstrates that Dox inhibits CASMC proliferation by blocking cell cycle progression from the G(0)/G(1) phase to the S phase. This G(1)-->S blockade likely results from an inhibition of mitogen-induced Rb hyperphosphorylation through prevention of p27 downregulation. /Salt not specified/|For more Mechanism of Action (Complete) data for DOXAZOSIN MESYLATE (6 total), please visit the HSDB record page.

Treatment of overdose: Treatment of circulatory failure by placing the patient the supine position and elevating the legs is most important; if shock is present, additional measures are necessary. Volume expanders may be used to treat shock, followed, if necessary, by administration of a vasopressor. Symptomatic, supportive treatment and monitoring of fluid and electrolyte status.

1 (4-Amino-6,7-dimethoxy-2-quinazolinyl)-4-((2,3-dihydro-1,4-benzodioxin-2-yl)carbonyl)piperazine

Alfadil; Benur; Cardenalin; Cardular; Cardura; Carduran; Diblocin; Normothen; Supressin; Zoxan.

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