Doxazosin (Page 4 of 5)
13.2 Animal Toxicology and Pharmacology
An increased incidence of myocardial necrosis or fibrosis was observed in long-term (6 to 12 months) studies in rats and mice (exposure 8 times human AUC exposure in rats and somewhat equivalent to human Cmax exposure in mice). Findings were not seen at lower doses. In dogs no cardiotoxicity was observed following 12 months of oral dosing at doses that resulted in maximum plasma concentrations (Cmax ) 14 times the Cmax exposure in humans receiving a 12 mg/day therapeutic dose or in Wistar rats at Cmax exposures 15 times human Cmax exposure. There is no evidence that similar lesions occur in humans.
14 CLINICAL STUDIES
14.1 Benign Prostatic Hyperplasia (BPH)
The efficacy of doxazosin was evaluated extensively in over 900 patients with BPH in double-blind, placebo-controlled trials. Doxazosin treatment was superior to placebo in improving patient symptoms and urinary flow rate. Significant relief with doxazosin was seen as early as one week into the treatment regimen, with doxazosin tablets-treated patients (N = 173) showing a significant (p<0.01) increase in maximum flow rate of 0.8 mL/sec compared to a decrease of 0.5 mL/sec in the placebo group (N = 41). In long-term studies, improvement was maintained for up to 2 years of treatment. In 66% to 71% of patients, improvements above baseline were seen in both symptoms and maximum urinary flow rate.
In three placebo-controlled studies of 14 to 16 weeks’ duration, obstructive symptoms (hesitation, intermittency, dribbling, weak urinary stream, incomplete emptying of the bladder) and irritative symptoms (nocturia, daytime frequency, urgency, burning) of BPH were evaluated at each visit by patient-assessed symptom questionnaires. The bothersomeness of symptoms was measured with a modified Boyarsky questionnaire. Symptom severity/frequency was assessed using a modified Boyarsky questionnaire or an AUA-based questionnaire. Uroflowmetric evaluations were performed at times of peak (2 to 6 hours post-dose) and/or trough (24 hours post-dose) plasma concentrations of doxazosin.
The results from the three placebo-controlled studies (N = 609) showing significant efficacy with 4 mg and 8 mg doxazosin are summarized in Table 3. In all three studies, doxazosin resulted in statistically significant relief of obstructive and irritative symptoms compared to placebo. Statistically significant improvements of 2.3 mL/sec to 3.3 mL/sec in maximum flow rate were seen with doxazosin in Studies 1 and 2, compared to 0.1 mL/sec to 0.7 mL/sec with placebo.
Table 3. SUMMARY OF EFFECTIVENESS DATA IN PLACEBO-CONTROLLED TRIALS
In one fixed-dose study (Study 2), doxazosin therapy (4 mg to 8 mg, once daily) resulted in a significant and sustained improvement in maximum urinary flow rate of 2.3 mL/sec to 3.3 mL/sec (Table 3) compared to placebo (0.1 mL/sec). In this study, the only study in which weekly evaluations were made, significant improvement with doxazosin versus placebo was seen after one week. The proportion of patients who responded with a maximum flow rate improvement of ≥ 3 mL/sec was significantly larger with doxazosin (34% to 42%) than placebo (13% to 17%). A significantly greater improvement was also seen in average flow rate with doxazosin (1.6 mL/sec) than with placebo (0.2 mL/sec). The onset and time course of symptom relief and increased urinary flow from Study 1 are illustrated in Figure 1.
14.2 Hypertension
In a pooled analysis of placebo-controlled hypertension studies with about 300 hypertensive patients per treatment group, doxazosin, at doses of 1 mg to 16 mg given once daily, lowered blood pressure at 24 hours by about 10/8 mmHg compared to placebo in the standing position and about 9/5 mmHg in the supine position. Peak blood pressure effects (1 to 6 hours) were larger by about 50% to 75% (i.e. trough values were about 55% to 70% of peak effect), with the larger peak-trough differences seen in systolic pressures. There was no apparent difference in the blood pressure response of Caucasians and blacks or of patients above and below age 65. In the same patient population, patients receiving doxazosin gained a mean of 0.6 kg compared to a mean loss of 0.1 kg for placebo patients.
PLACEBO (N=85) | Doxazosin (N=183) | |||
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| ||||
Sitting BP (mmHg ) | Baseline | Change | Baseline | Change |
Systolic | 128.4 | –1.4 | 128.8 | –4.9* |
Diastolic | 79.2 | –1.2 | 79.6 | –2.4* |
Standing BP (mmHg) | Baseline | Change | Baseline | Change |
Systolic | 128.5 | –0.6 | 128.5 | –5.3* |
Diastolic | 80.5 | –0.7 | 80.4 | –2.6* |
16 HOW SUPPLIED/STORAGE AND HANDLING
Doxazosin tablets, USP are available as tablets for oral administration. Each tablet contains doxazosin mesylate, USP equivalent to 1 mg, 2 mg, 4 mg or 8 mg of doxazosin.
The 1 mg tablets are available as white to off-white caplet-shaped tablets, debossed with “AC 356” on one side and scored on the other side. They are supplied as follows:
- Bottles of 100 with a child-resistant closure, NDC 0832-0356-11
The 2 mg tablets are available as white to off-white round tablets, debossed with “AC” and “357” on the scored side and plain on the other side. They are supplied as follows:
- Bottles of 100 with a child-resistant closure, NDC 0832-0357-11
The 4 mg tablets are available as white to off-white round tablets, debossed with “AC 358′ on the scored side and plain on the other side. They are supplied as follows:
- Bottles of 100 with a child-resistant closure, NDC 0832-1358-11
The 8 mg tablets are available as white to off-white caplet-shaped tablets, debossed with “AC 359” on one side and scored on other side. They are supplied as follows:
- Bottles of 100 with a child-resistant closure, NDC 0832-1359-11
Recommended Storage: Store at 25°C (77°F), excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
17 PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Postural Hypotension
Advise patients of the possibility of syncopal and orthostatic symptoms, especially at the initiation of therapy, and urged to avoid driving or hazardous tasks for 24 hours after the first dose, after a dosage increase, and after interruption of therapy when treatment is resumed. Advise patients to report symptoms to their healthcare provider.
Priapism
Advise patients of the possibility of priapism and to seek immediate medical attention if symptoms occur.
Distributed by
UPSHER-SMITH LABORATORIES, LLC Maple Grove, MN 55369
Revised: 7/2021
This Patient Information has been approved by the U.S. Food and Drug Administration.Revised 0518 |
Patient Information Doxazosin Tablets, USP (dox-AZE-oh sin) |
What are doxazosin tablets? Doxazosin tablets are a prescription medicine that contains doxazosin mesylate and is called an “alpha-blocker”. Doxazosin tablets are used to treat:
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Who should not take doxazosin tablets?Do not take doxazosin tablets if you:
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What should I tell my healthcare provider before taking doxazosin tablets?Before taking doxazosin tablets, tell your healthcare provider about all of your medical conditions, including if you:
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How should I take doxazosin tablets?
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What should I avoid while taking doxazosin tablets?Do not drive or perform any hazardous task until at least 24 hours after you have taken doxazosin tablets if you are taking:
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What are the possible side effects of doxazosin tablets?Doxazosin tablets may cause serious side effects, including:
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General information about the safe and effective use of doxazosin tablets. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use doxazosin tablets for a condition for which it was not prescribed. Do not give doxazosin tablets to other people, even if they have the same symptoms you have. It may harm them.This Patient Information leaflet summarizes the most important information about doxazosin tablets. For more information, ask your healthcare provider. You can ask your healthcare provider or pharmacist for information that is written for healthcare professionals. |
What are the ingredients in doxazosin tablets?Active ingredient: doxazosin mesylateInactive ingredients: microcrystalline cellulose, anhydrous lactose, sodium starch glycolate, magnesium stearate and sodium lauryl sulfate.Distributed byUPSHER-SMITH LABORATORIES, LLC Maple Grove, MN 55369For more information, go to www.upsher-smith.com or call 1-888-650-3789. |
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