Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Doxazosin”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1999

Effects of doxazosin in the gastrointestinal therapeutic system formulation versus doxazosin standard and placebo in mild-to-moderate hypertension. Doxazosin Investigators' Study Group.

The alpha 1-blocker doxazosin is a well-established therapy for hypertension and benign prostatic hyperplasia; however, in its standard form, a multiple-step titration regimen is usually required. The new gastrointestinal therapeutic system (GITS) formulation of doxazosin greatly minimizes the need for titration by changing drug-delivery rate and the pharmaco-kinetic profile. To demonstrate this in hypertensive patients, we assessed the effects of doxazosin GITS 4 or 8 mg once daily versus doxazosin standard 1-8 mg once daily, and placebo, in an integrated analysis of two multicenter, double-blind, randomized, parallel-group trials. Each trial included a 2-week washout period and 12 weeks of therapy. One study compared doxazosin GITS, doxazosin standard, and placebo in 392 patients with mild hypertension [blood pressure (BP) 95-105/ < or = 180 mm Hg]; the other study compared doxazosin GITS with doxazosin standard in 315 patients with mild-to-moderate hypertension (BP 95-115/ < or = 220 mm Hg). The primary outcome measure was the proportion of responders (sitting diastolic BP < 90 mm Hg or 10-mm Hg decrease from baseline 24 h after the dose) at the final visit for the per-protocol population. Mean baseline BP and heart rate were well matched in each group. Approximately 64% of patients with doxazosin GITS (198 of 309 patients) and 68% with doxazosin standard (207 of 304 patients) achieved goal BP response at the final visit versus 36% with placebo (25 of 70 patients; p < 0.05). The majority with doxazosin GITS (60%) remained at the initial 4-mg starting dose. Doxazosin GITS was as effective as doxazosin standard, and both were more effective than placebo in controlling BP in mild-to-moderate hypertension. Doxazosin GITS was well tolerated, and fewer patients with the GITS formulation discontinued therapy because of side effects compared with doxazosin standard or placebo. Syncope was not reported with doxazosin GITS. Whereas the efficacy of doxazosin GITS at 4 or 8 mg is equivalent to that of the standard regimen in this combined analysis, the GITS formulation appears to eliminate the need for titration in most patients.

Adult↗
PubMed2001

A combined analysis of double-blind trials of the efficacy and tolerability of doxazosin-gastrointestinal therapeutic system, doxazosin standard and placebo in patients with benign prostatic hyperplasia.

OBJECTIVE: To report an integrated analysis of two previous studies fully characterizing the clinical utility of the controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin in the treatment of benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Two pivotal randomized, double-blind studies of doxazosin GITS for BPH were assessed by an integrated analysis. Both studies included a 2-week washout period, a 2-week single-blind placebo run-in phase, and a 13-week double-blind treatment phase. One study compared doxazosin GITS, doxazosin standard (-S) and placebo in 795 men; the other compared doxazosin GITS and doxazosin-S in 680 men. Doxazosin GITS was initiated at 4 mg once daily and titrated to 8 mg once daily after 7 weeks, and doxazosin-S was initiated at 1 mg once daily and titrated to a maximum of 8 mg once daily over 7 weeks as needed to achieve optimal symptom control. The primary outcome measures were mean changes from baseline to the final visit for the International Prostate Symptom Score (IPSS) and maximum urinary flow rate (Qmax) in the per-protocol population. Numerous symptom- and urinary-related secondary outcomes were assessed, as were effects of therapy on male erectile dysfunction measured using the International Index of Erectile Function (IIEF) in one study. RESULTS: Both doxazosin GITS and doxazosin-S significantly improved the symptoms of BPH, as shown by a 45% reduction for each in total IPSS from baseline to final visit, compared with a 34% reduction in patients on placebo. Doxazosin GITS and doxazosin-S produced comparable improvements in Qmax that were significantly greater than with placebo, with a greater improvement sooner after treatment with doxazosin GITS than with doxazosin-S. Nearly half of the patients on doxazosin GITS had symptom relief at the 4-mg starting dose. A similar number of patients in both doxazosin groups were titrated to the maximum dose. Secondary outcomes were consistent with the primary effects. Both doxazosin GITS and doxazosin-S produced significant improvements in sexual function according to IIEF scores among those with dysfunction at baseline. The overall incidence of adverse events was similar among patients treated with doxazosin GITS and placebo, and slightly lower than those on doxazosin-S. There was no apparent difference in the type of adverse events reported for the two formulations of doxazosin, although most adverse events were reported at a lower frequency with doxazosin GITS. CONCLUSION: Doxazosin GITS is significantly more effective than placebo in reducing the clinical symptoms of BPH and improving Qmax, and as effective as doxazosin-S. Both doxazosin formulations improved sexual function in patients with BPH and sexual dysfunction at baseline. Doxazosin GITS produced a therapeutic effect equivalent to that of doxazosin-S, but with fewer titration steps and a slightly lower overall incidence of adverse events.

Adrenergic alpha-Antagonists↗
PubMed2000

Double-blind trial of the efficacy and tolerability of doxazosin in the gastrointestinal therapeutic system, doxazosin standard, and placebo in patients with benign prostatic hyperplasia.

BACKGROUND: The alpha(1)-blocker doxazosin mesylate is an established efficacious and welltolerated treatment for benign prostatic hyperplasia (PBH). However, its clinical utility can be limited by the need for multiple titration steps, starting at an initial dose of 1 mg, increased up to 8 mg once daily, to achieve optimal therapeutic response. A new controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin mesylate enhances the pharmacokinetic profile and drug delivery rate, reducing the plasma doxazosin mesylate peak-to-trough ratio and minimizing the need for titration. OBJECTIVE: A study was conducted to assess the effects of doxazosin GITS 4 or 8 mg once daily, doxazosin standard 1 mg to 8 mg once daily, and placebo, in 795 men with BPH. This randomized, double-blind, multicenter Scandinavian study included a 2-week washout period, 2-week single-blind placebo run-in phase, and 13-week double-blind treatment phase. Doxazosin GITS was initiated at 4 mg once daily and titrated to 8 mg once daily after 7 weeks, if indicated, and doxazosin standard was initiated at 1 mg once daily, titrated to 2 mg after 1 week, to 4 mg at 3 weeks, and to 8 mg at 7 weeks if indicated, to achieve symptom control. The primary outcome measures were mean changes from baseline to the final visit for International Prostate Symptom Score (I-PSS) and maximum urinary flow rate adjusted for baseline values. RESULTS: Both doxazosin GITS and doxazosin standard significantly improved the symptoms of BPH, as evidenced by least-squares mean reductions in total I-PSS of -8.0+/-0.3 and -8.4+/-0.3 from baseline, respectively, compared with a reduction of -6.0+/-0.4 in patients on placebo. Doxazosin GITS and doxazosin standard produced clinically comparable improvements in maximum urinary flow rates, with a greater improvement observed earlier following treatment with doxazosin GITS than with doxazosin standard. Both active treatments produced significantly greater increases in maximum urinary flow rate compared with placebo. Nearly half of the patients on doxazosin GITS achieved symptom relief at the 4-mg starting dose. A similar number of patients in both doxazosin groups were titrated to the maximum dose of 8 mg for both formulations. The overall incidence of adverse events was similar among patients treated with doxazosin GITS and placebo, and slightly higher in those on doxazosin standard. There was no apparent difference in the type of adverse events reported for the two formulations of doxazosin, although most adverse events were reported at a lower frequency with doxazosin GITS. CONCLUSIONS: Doxazosin GITS is significantly more effective than placebo in reducing the clinical symptoms of BPH and improving maximum urinary flow rate, and as effective as doxazosin standard. A therapeutic effect equivalent to that of doxazosin standard was achieved with doxazosin GITS with fewer titration steps, in a manner that appeared to be better tolerated. Because treatment with doxazosin GITS starts with an effective dose for many patients, it is likely that this clinical profile will result in the need for fewer patient visits than with doxazosin standard therapy.

Adrenergic alpha-Antagonists↗
PubMed2005

Doxazosin GITS versus standard doxazosin in mild to moderate hypertension.

BACKGROUND: The selective alpha 1-adrenoceptor antagonist doxazosin in both standard formulation and gastrointestinal therapeutic system (GITS) controlled-release formulation is effective for hypertension without having a negative impact on serum lipids. This study was designed to compare the relative efficacy of these two formulations of doxazosin on clinic and ambulatory blood pressure and serum lipids in patients with mild to moderate hypertension. METHODS: Hypertensive patients aged 18-70 years (n = 335) were evaluated in a multi-center prospective randomized study. Following a 2-week placebo run-in phase, patients were randomized to receive doxazosin 2 or 4 mg, with dose titration, or doxazosin GITS 4 mg, no dose titration, for 9 weeks. RESULTS: Both doxazosin formulations reduced clinic diastolic and systolic blood pressure from baseline (P < 0.0001). Doxazosin GITS and doxazosin 4 mg had similar blood pressure-lowering effects. Doxazosin GITS reduced sitting diastolic and systolic blood pressure compared with doxazosin 2 mg (P < 0.01 for both). A greater proportion of the doxazosin GITS group reached goal blood pressure (< or = 140/90 mm Hg) after 9 weeks compared with the doxazosin 2-mg group. All doses of doxazosin reduced 24-h and daytime (7:00 am to 10:00 pm) ambulatory blood pressure from baseline (all P < 0.01). Doxazosin GITS significantly reduced nighttime (10:00 pm to 7:00 am) ambulatory blood pressure from baseline. A neutral effect on serum lipids was observed with doxazosin. CONCLUSIONS: Doxazosin GITS and doxazosin were effective in reducing clinic and ambulatory blood pressure. The GITS formulation reduced the need for dose titration. Both doxazosin formulations were well tolerated.

Adolescent↗
PubMed1999

Doxazosin GITS compared with doxazosin standard and placebo in patients with mild hypertension.

Doxazosin, an effective treatment for mild-to-moderate hypertension and benign prostatic hyperplasia, in its standard formulation requires a multiple-step titration regimen to minimize the potential for first-dose effects. A new controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin was developed to enhance the pharmacokinetic profile, significantly reducing serum peak-to-trough ratios, thereby minimizing the need for titration. We assessed the efficacy and tolerability of doxazosin GITS compared with doxazosin standard and placebo in a prospective, randomized, double-blind, parallel-group, dose-titration, multicenter study of 392 patients with mild hypertension (blood pressure [BP] < or = 180/95-105 mmHg). Patients were randomized to doxazosin GITS, doxazosin standard, or placebo in 2:2:1 manner. The primary outcome measure was the proportion of patients in the per-protocol analysis (PPA) who achieved goal BP response (sitting BP < or = 90 mmg or 10 mmHg decrease from baseline at 24 h postdose at the final evaluable visit). Goal BP response in the intention-to-treat (ITT) population and prespecified BP and/or heart rate changes in the PPA and/or ITT population were also analyzed. Tolerability was assessed throughout the study. Doxazosin GITS and doxazosin standard produced comparable goal BP responses superior to that of placebo, with 92 of 156 patients (59.0%) on doxazosin GITS and 86 of 152 patients (56.6%) on doxazosin standard in the PPA population achieving goal BP response 24 hours postdose on the final visit, compared with 25 of 70 patients (35.7%) on placebo. Both active treatments produced mean significant BP reductions compared with baseline and placebo (p < 0.001). The most commonly reported side effects were headache, dizziness, and asthenia. No syncope was reported in the doxazosin GITS group; two cases were observed in the doxazosin standard group and one case in the placebo group. Doxazosin GITS was well tolerated and as effective as doxazosin standard in patients with mild hypertension, producing well-tolerated, comparable BP reductions with minimal need for titration. Both active treatments were clinically and statistically superior to placebo.

Adult↗
PubMed2000

[Doxazosin in the gastrointestinal therapeutic system (GITS) and doxazosin standard in patients with benign prostatic hyperplasia. Double-blind trial of efficacy and tolerability].

BACKGROUND AND METHOD: This randomized, doubleblind, multicenter, parallel-group, placebo-baseline study compared the effects of doxazosin GITS 4 mg or 8 mg once daily with doxazosin standard 1 mg to 8 mg once daily in 678 men with benign prostatic hyperplasia (BPH). Following a 2-week washout period and a 2-week, single-blind, placebo run-in phase, patients were randomized to 13 weeks of double-blind treatment with doxazosin GITS, initiated at 4 mg once daily and titrated to 8 mg once daily after 7 weeks, if needed, and doxazosin standard, initiated at 1 mg once daily, titrated to 2 mg after 1 week, to 4 mg at 3 weeks, and to 8 mg at 7 weeks if needed. The primary outcome measures were mean changes from baseline to the final visit for International Prostate Symptom Score (I-PSS) and maximum urinary flow rate in the per-protocol analysis (PPA) population. Secondary outcomes included other aspects of BPH symptoms and urinary flow; and assessment of sexual function in the PPA and intent-to-treat populations, as measured by the International Index of Erectile Function (IIEF). RESULTS: Doxazosin GITS and doxazosin standard produced clinically and statistically significant equivalent reductions in BPH symptoms, including least-square mean decreases in total I-PSS of -8.1 +/- 0.3 and -7.9 +/- 0.3 from baseline, respectively (p < 0.001 vs baseline for each). Both therapies significantly improved maximum urinary flow rates by 2.7 +/- 0.3 ml/s (least-squares mean change from baseline, p < 0.001). The beneficial effects of both therapies on secondary parameters of symptoms and urinary flow were consistent with these findings. Significant improvements in sexual function were observed with both therapies among individuals with sexual dysfunction at baseline. Nearly half of patients on doxazosin GITS achieved BPH symptom relief at the initial 4-mg dose.A similar number of patients in both doxazosin groups were titrated to the maximum dose of 8 mg for both formulations. While both agents were well tolerated, the incidence of at least one treatment-emergent adverse event was significantly lower among patients treated with doxazosin GITS (p = 0.003). CONCLUSIONS: Doxazosin GITS and doxazosin standard produced comparable significant reductions in BPH symptoms and improvements in maximum urinary flow rates. A therapeutic effect equivalent to that of doxazosin standard was achieved with doxazosin GITS with fewer titration steps and enhanced tolerability. Both formulations of doxazosin improved sexual function in individuals with dysfunction at baseline.

Adrenergic alpha-Antagonists↗
PubMed2000

[Cardura XL--a unique drug formulation--doxazosine administered in a slow-release form (doxazosine GITS)].

An active component in the tablet Cardura XL is doxazosine. Doxazosine belongs to the third generation of alpha 1-adrenolytics. It is a blocker of post-synaptic alpha 1-receptors both in humans and in animals. It is a long acting preparation. A tablet cover of Cardura XL is built of two layers (GITS system). It has enabled administration of doxazosine once a day. A great advance of the GITS system is a verly slow and systematic release of the drug from the tablet. This release is independent of pH of gastro-intestinal content or peristalsis. After administration of the tablet of Cardura XL, over 85% of the drug is released after 12 hours and the release ends after 12-16 hours. Maximal serum drug level after administration of doxazosine GITS is observed after 14-16 hours. Higher maximal serum drug level is achieved when the drug is administered together with a meal. Using doxazosine in the GITS form, minimal and maximal serum drug levels during the whole 24 hours differ non significantly. GITS technology enabled achieving stable daily serum drug concentration. Introducing doxazosine GITS caused: 1. decrease of Cmax; 2. elongation of Tmax; and 3. decrease of Cmin compared to doxazosine. It became possible due to gradual absorption of the preparation from gastrointestinal tract and improved coefficient of the drug fluctuation. It should be stated that the described pharmacological differences of doxazosine GITS in younger and elderly, in female and male patients do not influence significantly initial dosing of the drug. Stenosis of the gastrointestinal tract or chronic diarrhea affecting bowel passage of the drug, change its therapeutic effect. An effect of doxazosine GITS, doxazosine and placebo on blood pressure was studied in 392 patients with mild and moderate hypertension (< or = 220/95-115 mm Hg). Doxazosine GITS similarly to doxazosine effectively decreases blood pressure. The value of diastolic blood pressure decrease increases together with the therapy duration. Use of the unique GITS technology assures stable daily serum drug concentration. It results in: mild but permanent decrease of the blood pressure, decreased risk of side-effects, including orthostatic hypotony. Based on the performed post-registration studies it should be stated that doxazosine GITS is not only a very effective but also a safe preparation, which may be administered once daily. The treatment should be initialized with a dose of 4 mg daily. In as much as 60% of the patients with mild or moderate arterial hypertension, an initial dose (4 mg of Cardura XL) effectively lowers blood pressure. Taking into consideration unique features of the described preparation, it is worth thinking of Cardura XL while initializing or switching therapy in hypertensive patients. Cardura XL, due to favourable metabolic effects as well as the unique GITS technology seems to be the drug particularly suitable in hypertensive patients with accompanying dyslipidaemia, diabetes mellitus type 2 and/or benign prostata hypertrophy.

Adrenergic alpha-Antagonists↗
PubMed2002

A postmarketing, open-label study to evaluate the tolerability and effectiveness of replacing standard-formulation doxazosin with doxazosin in the gastrointestinal therapeutic system formulation in adult patients with hypertension.

BACKGROUND: The antihypertensive doxazosin works to decrease perivascular muscular tone, causing vasodilatation and hence a decrease in peripheral vascular resistance. To prevent the sharp decrease in blood pressure (BP), syncope, and other postural effects that may occur at the beginning of therapy with this drug, the dose must be adjusted. A new formulation, doxazosin gastrointestinal therapeutic system (GITS), allows slow release of the active agent so therapeutic serum levels are reached within 24 hours, rendering dose adjustment unnecessary and eliminating any first-dose effects. OBJECTIVES: The goals of this study were to evaluate the tolerability and effectiveness of (1) using doxazosin in the standard and new GITS formulations in adult patients with hypertension who either had uncontrolled or newly diagnosed disease, and (2) replacing standard-formulation doxazosin with doxazosin in the GITS formulation. METHODS: This was a postmarketing, open-label, noncomparative, multicenter clinical study covering primary care patients diagnosed with essential uncontrolled arterial hypertension (AHT). Subjects could be patients who were undergoing drug therapy before enrollment or those diagnosed with AHT and/or treated for the disease for the first time on entering the study. The study covered a period of 6 to 9 months, divided into 2 phases. Phase 1 involved a minimum of 3 and maximum of 6 months of treatment with standard-formulation doxazosin. Phase 2 commenced with the changeover from standard-formulation doxazosin to the GITS formulation and lasted 12 weeks. The principal study variables included BP and the development of adverse events (AEs). At every visit, the patients were asked by an investigator whether they had suffered any AEs since the previous contact. RESULTS: Of the total of 4,512 patients initially enrolled, 3537 (78.4%) completed the study. A total of 285 patients were excluded for failing to comply with the inclusion criteria, leaving 4,227 patients for analysis. In most instances, premature withdrawal from the study (16.3% [690/4,227]) was due to loss to follow-up (37.2% [257/690]), followed by the development of AEs (27.8% [192/690]). Fifty-nine percent (2,493/4,226) of patients analyzed were men and 41.0% (1,733/4,226) were women (sex data not recorded for 1 patient), with a mean age of 62.4 years (SD, 10.6). Among the patients participating, 54.8% (2,316/4,227) presented with some type of associated disease. The percentage of patients undergoing monotherapy was 70.7% (2,987/4,227); the remainder (29.3% [1,240/4,227]) underwent a combined-therapy regimen using another antihypertensive drug in conjunction with doxazosin. The mean initial systolic and diastolic BPs were 160 +/- 10.63 mm Hg and 95.26 +/- 7.21 mm Hg, respectively. Reduction in systolic BP was 20.9 mm Hg in phase 1 and 3.8 mm Hg in phase 2. In the case of diastolic BP, the reduction was 13.3 mm Hg in phase 1 and 2.6 mm Hg in phase 2. The percentage of patients with controlled disease was 47.9% (1,891/3,949) by the end of phase 1 and 63.4% (2,242/3,537) by the end of phase 2. A total of 322 (7.6%) patients presented with 343 AEs. 37 (0.9%) of which were deemed severe (0.6% in phase 1 and 0.3% in phase 2). Limitations included the following: (1) the design of this study did not allow comparison of the 2 formulations regarding effectiveness or tolerability: (2) the patients who remained in the study after phase 1 were those less susceptible to toxicity from doxazosin; and (3) it is probable that the nonresponders were more likely to drop out of the study. CONCLUSIONS: Doxazosin in the standard formulation was effective and well tolerated for the purpose of lowering BP. Patients who tolerated the standard formulation also tolerated the switch to the GITS formulation. Finally, this substitution did not negatively impact the effectiveness of treatment of AHT.

Adult↗
PubMed2005

Efficacy of extended-release doxazosin and doxazosin standard in patients with concomitant benign prostatic hyperplasia and sexual dysfunction.

OBJECTIVE: To report a comprehensive retrospective analysis of the favourable effects of doxazosin extended-release (XL) and doxazosin standard on the sexual health of patients with comorbid benign prostatic hyperplasia (BPH) and erectile dysfunction (ED), augmenting a previous study of 680 patients with symptomatic BPH. PATIENTS AND METHODS: Men with BPH and aged 50-80 years participated in a randomized, double- blind, double-dummy, parallel-group, multicentre trial, completing a 2-week, single-blind, placebo run-in period before receiving doxazosin XL 4 or 8 mg once daily or doxazosin standard 1-8 mg once daily for 13 weeks. Baseline sexual function and changes from baseline after treatment with doxazosin were evaluated from responses of the International Index of Erectile Function (IIEF) questionnaire (with dysfunction defined as a score of < or = 3 for any question) and the five domains for erectile function (intercourse satisfaction, orgasmic function, sexual desire and overall sexual satisfaction). RESULTS: Of 680 patients randomized into the trial, 237 (35%) had ED at baseline; in these patients there were statistically and clinically significant improvements in each of the five IIEF domains with XL and standard doxazosin (P < or = 0.0019), with the range of improvement being from 13% to 41%. There were no significant differences between treatment groups. Doxazosin XL consistently improved sexual function, as assessed by the individual questions of the IIEF questionnaire. There was no statistically significant difference between groups for any sexual function question analysed. CONCLUSION: Doxazosin XL and standard improved sexual function in men with concomitant BPH and ED at baseline. This may represent an action independent of relieving lower urinary tract symptoms, because the beneficial effect of doxazosin was reported in patients with no symptomatic BPH.

Adrenergic alpha-Antagonists↗
PubMed2003

Efficacy and tolerability of doxazosin and finasteride, alone or in combination, in treatment of symptomatic benign prostatic hyperplasia: the Prospective European Doxazosin and Combination Therapy (PREDICT) trial.

OBJECTIVES: To evaluate the efficacy and tolerability of the selective alpha(1)-adrenergic antagonist doxazosin and the 5-alpha-reductase inhibitor finasteride, alone and in combination, for the symptomatic treatment of benign prostatic hyperplasia. METHODS: In a prospective, double-blind, placebo-controlled trial, 1095 men aged 50 to 80 years were randomized to treatment for 52 weeks with doxazosin, finasteride, the combination of doxazosin and finasteride, or placebo. The dose of finasteride (or its matched placebo) was 5 mg/day. Doxazosin (or its matched placebo) was initiated at 1 mg/day, and titrated up to a maximum of 8 mg/day over approximately 10 weeks according to the response of the maximal urinary flow rate (Qmax) and International Prostate Symptom Score (IPSS). The IPSS and Qmax were assessed at baseline and at weeks 10, 14, 26, 39, and 52 or at the endpoint. RESULTS: An intent-to-treat analysis of 1007 men showed doxazosin and doxazosin plus finasteride combination therapy produced statistically significant improvements in total IPSS and Qmax compared with placebo and finasteride alone (P <0.05). Finasteride alone was not significantly different statistically from placebo with respect to total IPSS and Qmax. All treatments were generally well tolerated. CONCLUSIONS: Doxazosin was effective in improving urinary symptoms and urinary flow rate in men with benign prostatic hyperplasia, and was more effective than finasteride alone or placebo. The addition of finasteride did not provide further benefit to that achieved with doxazosin alone.

5-alpha Reductase Inhibitors↗
PubMed1991

An evaluation of the efficacy and safety of doxazosin in hypertension associated with renal dysfunction. The Japanese Doxazosin Study Group.

Doxazosin was administered once daily to 26 patients with renal hypertension or hypertension associated with renal dysfunction. Doxazosin produced a significant reduction in blood pressure that was stable throughout the treatment period. A significant change was not observed in heart rate. Blood pressure was "markedly decreased" or "decreased" in 80% of patients receiving doxazosin monotherapy, 78.6% of patients receiving combined therapy, and 79.2% of all the patients. The cumulative efficacy ratio according to final daily dose was 62.5% with 1 to 4 mg/day and 75.0% to 79.2% with 8 to 16 mg/day. Side effects were observed in three patients (12.0%), none of them severe, and all side effects disappeared with continued administration of doxazosin. Abnormal laboratory values in six items were observed in four patients. Serum creatinine and blood urea nitrogen values, which were regarded as renal function parameters, did not show significant changes, and no negative influence was observed with respect to doxazosin therapy. Overall clinical usefulness was considered "very useful" or "useful" in 80% of patients receiving doxazosin monotherapy, 78.6% of patients receiving combination therapy, and 79.2% of all patients. In conclusion, once-daily administration of doxazosin was considered a useful antihypertensive therapy for renal hypertension and hypertension associated with renal dysfunction.

Adult↗
PubMed2002

Doxazosin and hydrochlorothiazide equally affect arterial wall thickness in hypertensive males with hypercholesterolaemia (the DAPHNE study). Doxazosin Atherosclerosis Progression Study in Hypertensives in the Netherlands.

BACKGROUND: Observational studies suggest a synergistic effect of hypertension and hyperlipidaemia on the progression of atherosclerosis. The alpha-blocker doxazosin has favourable effects on plasma lipids, insulin resistance and blood pressure, while the diuretic hydrochlorothiazide (HCTZ) principally affects blood pressure and increases insulin resistance. METHODS: A randomised double-blind study over 36 months was performed to compare the effects of doxazosin and HCTZ on fasting lipids and on progression of peripheral atherosclerosis. Eighty males (45 to 70 years) with peripheral atherosclerotic disease and increased cholesterol levels (5.2-8.0 mmol/l) were treated for essential hypertension with either doxazosin (n = 41) or HCTZ (n = 39). Main outcome measures were arterial intima-media thickness (IMT) of the carotid and femoral arteries and fasting lipid parameters. RESULTS: In the doxazosin-treated group, significant changes were observed in the concentration of triglycerides (-13.7%, p < 0.01), HDLc (+25.7%, p < 0.05) and IDLc (-30.1%, P < 0.05). In the HCTZ-treated group no significant changes in plasma lipid levels were observed. On follow-up visits systolic blood pressure in the doxazosin-treated group was 6 mm higher than in the HCTZ group. Nevertheless, the groups treated with doxazosin or HCTZ showed no differential effect on IMT after three years of treatment (p = 0.8). A significant reduction of the IMT of combined carotid and femoral arterial walls was shown in both treatment groups (p < 0.005). CONCLUSIONS: Hypertension treatment with doxazosin or HCTZ resulted in a comparable change in arterial IMT after three years, in spite of differences in effect on plasma lipids. The study emphasises the importance of blood pressure control in patients with peripheral vascular disease and hypercholesterolaemia.

Aged↗
PubMed1993

Efficacy and safety of the alpha-1 blocker doxazosin in the treatment of benign prostatic hyperplasia. Analysis of 5 studies. Doxazosin Study Groups.

Controlled clinical studies have demonstrated that blockade of alpha 1-adrenergic receptors relaxes prostatic muscle tone and decreases the symptoms of benign prostatic hyperplasia (BPH). Doxazosin, a once-daily quinazoline derivative and postsynaptic alpha 1-adrenoceptor antagonist, proven as treatment for hypertension, was evaluated in the treatment of BPH in dosages of 1-16 mg. 456 BPH patients (287 doxazosin-treated and 169 placebo-treated) were evaluated for efficacy and safety in five double-blind, placebo-controlled clinical studies. Doxazosin treatment resulted in improvements in both urodynamic and symptomatic parameters associated with BPH. Efficacy was only assessed in 1, 2 and 4 mg. Adverse experiences were reported in 127 (44.3%) of the patients treated with doxazosin and in 49 (29%) of the patients treated with placebo. Fifteen (5.2%) doxazosin patients and 4 (2.4%) placebo patients withdrew from the studies due to adverse effects. Results from these five clinical trials demonstrate doxazosin is effective and safe and well tolerated in both normotensive and hypertensive patients with BPH.

Aged↗
PubMed1993

Doxazosin and captopril in mildly hypercholesterolemic hypertensive patients. The Doxazosin-Captopril in Hypercholesterolemic Hypertensives Study.

The evidence linking hypertension and hypercholesterolemia is strong and has fueled research into possible adverse effects of some antihypertensive agents on serum lipid profile. This multicenter, open, parallel study compares the effects of doxazosin and captopril on blood pressure, serum lipid levels, and quality of life in 224 hypercholesterolemic hypertensive patients. Blood pressure was significantly reduced in both treatment groups (p < 0.001) and was normalized (standing diastolic pressure < or = 90 mm Hg) in 73% of the doxazosin patients and 67% of the captopril group. Serum total cholesterol level was favorably reduced by both doxazosin (from 238 to 223 mg/dl, p < 0.001) and captopril (from 245 to 233 mg/dl, p < 0.001), whereas high density lipoprotein cholesterol concentration increased only in the doxazosin group (from 33 to 36 mg/dl, p < 0.001). The calculated 10-year risk for the development of coronary heart disease was reduced significantly (p < 0.001) by 28% in the doxazosin group and by 19% in the captopril group. The quality of life evaluation showed beneficial changes in both treatment groups. As a result of proven antihypertensive efficacy and a lack of unfavorable effects on lipid parameters and health status measures, these findings support the use of both doxazosin and captopril as agents of first choice in the treatment of hypertensive patients with associated lipid abnormalities.

Adult↗
PubMed2003

Safety and effectiveness of replacing standard doxazosin with doxazosin in the gastrointestinal therapeutic system (GITS) formulation in elderly hypertensive patients.

The objective of this paper is to evaluate the safety and effectiveness of using doxazosin standard formulation in elderly hypertensive patients who were either uncontrolled or newly diagnosed, and replacing standard doxazosin with doxazosin in the gastrointestinal therapeutic system (GITS) formulation. We designed a postmarketing surveillance, open-label non-comparative, multicentre, clinical study covering primary care patients aged 65 years or older diagnosed with essential uncontrolled arterial hypertension. The study covered a period of 6-9 months, divided into two phases. Phase I involved a minimum of three and maximum of six months in treatment with standard doxazosin; phase II began with the changeover from standard doxazosin to the GITS formulation and lasted 12 weeks. Of the 1705 patients initially enrolled, 1292 (75.8%) completed the study. Reduction in systolic blood pressure was 22.3 mmHg (13.7%) in phase I, and 3.9 mmHg (2.77%) in phase II; reduction in diastolic blood pressure was 12.4 mmHg (13.2%) in phase I, and 2.4 mmHg (2.9%) in phase II. The percentage of controlled patients was 40.5% (691/1705) by the end of phase I and 45.3% (776/1705) by the end of phase II. A total of 154 patients suffered adverse events (AE), 127 during phase I and 27 in phase II. We conclude that doxazosin in its two formulations is effective and safe for the purpose of lowering blood pressure in elderly patients.

Aged↗
PubMed2006

Comparison of doxazosin GITS and standard doxazosin in the treatment of high blood pressure.

OBJECTIVE: To examine (1) the relative therapeutic equivalence of 4 mg doxazosin gastrointestinal therapeutic system (DOX GITS) and 4 mg doxazosin standard (DOX-S4) and (2) the efficacy and safety of 4 mg DOX GITS versus 2 mg doxazosin standard (DOX-S2). PATIENTS: Male or female patients aged 18-80 diagnosed with mild-to-moderate essential hypertension (sitting diastolic blood pressure (DBP) 95-110 mmHg and systolic blood pressure (SBP) < 180 mmHg) were randomized into the study. METHODS: This double-blind, parallel, 9-week trial compared DOX-GITS with doxazosin standard (DOX-S) in 310 hypertensive patients. Following a 2-week placebo run-in phase, patients were randomized to receive DOX-GITS at 4 mg/d or DOX-S at 2 or 4 mg/d. DOX GITS dosage remained unchanged at 4 mg throughout the study. Titration in the DOX-S groups was initiated at Week 0 with 1 mg DOX-S and increased to 2 mg DOX-S at Week 1. Dosage in the DOX-S4 group was increased to 4 mg DOX-S at Week 3. Therapeutic equivalence was measured by the change from baseline in sitting diastolic BP (DBP). Efficacy was assessed using the change from baseline for all blood pressure measures. Safety analysis included evaluation of laboratory tests at clinic visits and adverse events (AEs). RESULTS: Therapeutic equivalences between DOX GITS and DOX-S4 and DOX-S2 were established at all study visits except for a significant difference in favor of DOX GITS at Week 1 (p = 0.019) when the dose of DOX-S was 1 mg. All groups had a significant decrease in BP at all study visits compared with baseline. The proportion of patients who reached goal sitting DBP (< 90 mmHg) was similar among the three treatment groups, except at Week 1, when more patients in the DOX GITS group had obtained the goal compared with those in the DOX-S2 group (40.6% vs. 22.3%; p = 0.005). The proportion of patients who reached sitting SBP (< 140 mmHg) goal was similar among groups. AE profiles among the groups were similar. CONCLUSION: DOX GITS was as effective as DOX-S in patients with mild-to-moderate hypertension. The improved pharmacokinetic profile of the GITS formulation compared with the standard formulation allows a therapeutic dose to be delivered earlier and without dose titration. Both formulations of doxazosin were well tolerated.

Adolescent↗
PubMed2006

High-performance liquid chromatographic determination of doxazosin in human plasma for bioequivalence study of controlled release doxazosin tablets.

A highly sensitive high-performance liquid chromatographic quantification method with fluorescence detection was developed and validated for the determination of doxazosin in human plasma. The developed method employed one-step extraction of doxazosin from plasma matrix with ethyl acetate using propranolol as an internal standard. Chromatographic separation was obtained within 8.0 min using a reverse-phase Capcell-Pak C(18) column (150 x 4.6 mm i.d., 5 microm) and the mobile phase consisted of methanol-water containing 10 mM perchloric acid and 1.8 mM sodium heptane sulfonic acid (50:50, v/v) and was set at a flow rate of 1.5 mL/min. The calibration curve constructed was linear in the range of 0.3-50.0 ng/mL. The proposed method achieved a lower limit of quantification of 0.3 ng/mL, better than the reported HPLC methods. Average recoveries of doxazosin and the internal standard from human plasma matrix were 87.0 and 85.9%, respectively. The present method was validated by evaluating the precision and accuracy for inter- and intraday variation in the concentration range 0.3-50 ng/mL. The precision values expressed as relative standard deviations in the inter- and intraday validation were 1.17-6.29 and 0.84-5.94%, respectively. This method was successfully applied to the bioequivalence study of two doxazosin controlled release tablets in healthy, male human subjects.

Chromatography, High Pressure Liquid↗
PubMed2006

Beneficial effects of extended-release doxazosin and doxazosin standard on sexual health.

The prevalence of benign prostatic hypertrophy (BPH) and erectile dysfunction (ED) both increase with age, and increasing evidence suggests a common cause rather than independent age-related changes. Arterial hypertension often accompanies these urological disorders, suggesting the possibility that increased alpha-adrenoceptor activity may be causal in all three conditions. As evidence for this model, alpha-adrenoceptor antagonists such as doxazosin produce therapeutically beneficial effects in lowering blood pressure, reducing prostate growth and BPH symptoms, and relieving ED. At postjunctional alpha(1)-receptors in the corpus cavernosa, noradrenaline causes vascular smooth muscle cell contraction, restricting blood flow, resulting in penile detumescence. Just as alpha-adrenoceptor antagonism results in systemic vasorelaxation to lower blood pressure, the same mechanism in the penis modulates the effects of noradrenaline to favour vasodilatation, resulting in improved erectile function. Increasing clinical evidence attests to the effectiveness of doxazosin in relieving ED, even in patients refractory to ED-specific treatment, as well as in reducing BPH symptoms and elevated blood pressure.

Adrenergic alpha-Antagonists↗