PRINCIPAL DISPLAY PANEL FOR 8 MG 100s

Representative sample of labeling (seeHOW SUPPLIED section of complete listing):

APOTEX CORP.

NDC 60505-0096-0 Doxazosin Tablets, USP8mgRx100 count

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 tablets treatment was superior to placebo in improving patient symptoms and urinary flow rate. Significant relief with doxazosin tablets 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 to 3.3 mL/sec in maximum flow rate were seen with doxazosin tablets in Studies 1 and 2, compared to 0.1 to 0.7 mL/sec with placebo.

Table 3

In one fixed-dose study (Study 2), doxazosin tablets therapy (4 to 8 mg, once daily) resulted in a significant and sustained improvement in maximum urinary flow rate of 2.3 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 tablets vs. 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 tablets (34 to 42%) than placebo (13 to 17%). A significantly greater improvement was also seen in average flow rate with doxazosin tablets (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.

Figure 1 – Study 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 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 tablets gained a mean of 0.6 kg compared to a mean loss of 0.1 kg for placebo patients.

TABLE 4 Mean Changes in Blood Pressure from Baseline to the Mean of the Final Efficacy Phase in Normotensives (Diastolic BP <90 mmHg) in Two Double-blind, Placebo-controlled U.S. Studies with doxazosin 1 to 8 mg once daily.

p ≤0.05 compared to placebo
	PLACEBO (N=85)	Doxazosin Tablets (N=183)
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

11 DESCRIPTION

Doxazosin mesylate is a quinazoline compound that is a selective inhibitor of the alpha1 subtype of alpha-adrenergic receptors. The chemical name of doxazosin mesylate is 1-(4-amino-6,7- dimethoxy-2-quinazolinyl)-4-(1,4-benzodioxan-2-ylcarbonyl) piperazine methanesulfonate. The empirical formula for doxazosin mesylate is C23H25N5O5 • CH4O3S and the molecular weight is 547.6. It has the following structure:


Doxazosin mesylate is freely soluble in dimethylsulfoxide, soluble in dimethylformamide, slightly soluble in methanol, ethanol, and water (0.8% at 25°C), and very slightly soluble in acetone and methylene chloride. Each doxazosin tablet, USP, for oral administration, contains 1 mg, 2 mg, 4 mg and 8 mg of doxazosin as the free base.

In addition, each doxazosin tablet, USP contains the following inactive ingredients: croscarmellose sodium, lactose monohydrate, magnesium stearate and microcrystalline cellulose.

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.

APOTEX INC.
DOXAZOSIN TABLETS, USP
1 mg, 2 mg, 4 mg and 8 mg

Manufactured by	Manufactured for
Apotex Inc.	Apotex Corp.
Toronto, Ontario	Weston, Florida
Canada M9L 1T9	USA 33326

Rev. 8

PATIENT INFORMATION
Doxazosin Tablets
(dox az' 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:

• the symptoms of benign prostatic hyperplasia (BPH)
• high blood pressure (hypertension)

It is not known if doxazosin tablets are safe and effective in children.

Who should not take doxazosin tablets?

Do not take doxazosin tablets if you:

• are allergic to doxazosin, other quinazolines, or any of the ingredients in doxazosin tablets. See the end of this Patient Information leaflet for a complete list of ingredients in doxazosin tablets.

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:

• have had low blood pressure, especially after taking other medicine. Signs of low blood pressure include fainting, dizziness, and lightheadedness.
• have any planned eye surgery
• have prostate cancer or a history of prostate cancer. Your healthcare provider may have you checked for prostate cancer before you start taking and while you take doxazosin tablets.
• have liver problems
• are pregnant or plan to become pregnant. It is not known if doxazosin tablets will harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known if doxazosin passes into your breastmilk. Talk to your healthcare provider about the best way to feed your baby if you take doxazosin tablets.

**Tell your healthcare provider about all the medicines you take,**including prescription and over-the-counter medicines, vitamins, and herbal supplements. Doxazosin tablets may affect the way other medicines work, and other medicines may affect the way doxazosin tablets work causing side effects.

Especially tell your healthcare provider if you take:

• other medicine for high blood pressure or medicine to treat erectile dysfunction (ED) called a phosphodiesterase type 5 (PDE-5) inhibitor. The use of doxazosin tablets with PDE-5 inhibitors can lead to a drop in blood pressure or to fainting.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I take doxazosin tablets?

• Take doxazosin tablets exactly as your healthcare provider tells you to take it.
• Your healthcare provider will tell you how much doxazosin tablets to take and when to take it.
• Your healthcare provider may need to change your dose of doxazosin tablets until it is the right dose for you.

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:

• your first dose of doxazosin tablets
• Doxazosin tablets for the first timeafteryour healthcare provider has increased your dose of doxazosin tablets
• Doxazosin tablets for the first timeafterany breaks (interruptions) in your treatment with doxazosin tablets

What are the possible side effects of doxazosin tablets?

Doxazosin tablets may cause serious side effects, including:

***A sudden drop in blood pressure,**especially when you first start treatment or when there is an increase in your dose of doxazosin tablets, is common but can also be serious. This may cause you to faint, or to feel dizzy or lightheaded. Your risk of having this problem may be increased if you take doxazosin tablets with certain other medicines that lower blood pressure including PDE-5 inhibitors. Your healthcare provider may monitor your blood pressure while you take doxazosin tablets. See "What should I avoid while taking doxazosin tablets?" ***Eye problems during cataract surgery.**A condition called Intraoperative Floppy Iris Syndrome (IFIS) can happen during cataract surgery if you take or have taken alpha-blockers such as doxazosin tablets. If you need to have cataract surgery, be sure to tell your healthcare provider if you take or have taken doxazosin tablets. ***A painful erection that will not go away.**Doxazosin tablets can cause a painful erection (priapism), which cannot be relieved by having sex. If this happens, get medical help right away. If priapism is not treated, you may not be able to get an erection in the future.

The most common side effects of doxazosin tablets are:

• weakness or lack of energy (asthenia)
• dizziness

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of doxazosin tablets. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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 mesylate

**Inactive ingredients:**croscarmellose sodium, lactose monohydrate, magnesium stearate and microcrystalline cellulose.

All registered trademarks in this document are the property of their respective owners.

APOTEX INC.
DOXAZOSIN TABLETS, USP
1 mg, 2 mg, 4 mg and 8 mg

Manufactured by	Manufactured for
Apotex Inc.	Apotex Corp.
Toronto, Ontario	Weston, Florida
Canada M9L 1T9	USA 33326

Revised: July 2024

Rev. 8