These Highlights Do Not Include All The Information Needed To Use Doxazosin Tablets Safely And Effectively. See Full Prescribing Information For Doxazosin Tablets.

Benign Prostatic Hyperplasia (BPH)

The incidence of adverse events has been ascertained from worldwide clinical trials in 965 BPH patients. The incidence rates presented below (Table 2) are based on combined data from seven placebo-controlled trials involving once-daily administration of doxazosin tablets in doses of 1 mg to 16 mg in hypertensives and 0.5 mg to 8 mg in normotensives. Adverse reactions occurring more than 1% more frequently in BPH patients treated with doxazosin tablets versus placebo are summarized in Table 1.

Other adverse reactions occurring less than 1% more frequently in BPH patients treated with doxazosin tablets versus placebo but plausibly related to doxazosin tablets include: palpitations.

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].

Alpha ₁antagonists, including doxazosin, have been associated with priapism (painful penile erection, sustained for hours and unrelieved by sexual intercourse or masturbation). This condition can lead to permanent impotence if not promptly treated.

Experience with doxazosin tablets overdosage is limited. Two adolescents, who each intentionally ingested 40 mg doxazosin tablets with diclofenac or acetaminophen, were treated with gastric lavage with activated charcoal and made full recoveries. A two-year-old child who accidently ingested 4 mg doxazosin tablets was treated with gastric lavage and remained normotensive during the five-hour emergency room observation period. A six-month-old child accidentally received a crushed 1 mg tablet of doxazosin tablets and was reported to have been drowsy. A 32-year-old female with chronic renal failure, epilepsy, and depression intentionally ingested 60 mg doxazosin tablets (blood level = 0.9 mcg/mL; normal values in hypertensives = 0.02 mcg/mL); death was attributed to a grand mal seizure resulting from hypotension. A 39-year-old female who ingested 70 mg doxazosin tablets, alcohol, and Dalmane ^®(flurazepam) developed hypotension which responded to fluid therapy.

The oral LD ₅₀of doxazosin is greater than 1000 mg/kg in mice and rats. The most likely manifestation of overdosage would be hypotension, for which the usual treatment would be intravenous infusion of fluid. As doxazosin is highly protein bound, dialysis would not be indicated.

Doxazosin is a quinazoline compound that is a selective inhibitor of the alpha ₁subtype 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 molecular formula for doxazosin mesylate is C ₂₃H ₂₅N ₅O ₅∙ CH ₄O ₃S and the molecular weight is 547.6. It has the following structure:

Doxazosin 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. Doxazosin tablets, USP are available as tablets for oral use and contains 1 mg, 2 mg, 4 mg and 8 mg of doxazosin as the free base.

The inactive ingredients for all tablets are: microcrystalline cellulose, anhydrous lactose, sodium starch glycolate, magnesium stearate and sodium lauryl sulfate.

Doxazosin tablets are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including this drug.

Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).

Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.

Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.

Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.

Doxazosin tablets may be used alone or in combination with other antihypertensives.

The initial dosage of doxazosin tablets is 1 mg given once daily. Daily dosage may be doubled up 16 mg once daily, as needed, to achieve the desired reduction in blood pressure.

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.

The safety and effectiveness of doxazosin have not been established in children.

The use of doxazosin tablets is contraindicated in patients with a hypersensitivity to doxazosin, other quinazolines (e.g., prazosin, terazosin), or any of its components.

Carcinoma of the prostate causes many of the symptoms associated with BPH and the two disorders frequently co-exist. Carcinoma of the prostate should therefore be ruled out prior to commencing therapy with doxazosin tablets for the treatment of BPH.

The most commonly reported adverse reactions from clinical trials are fatigue, malaise, hypotension, and dizziness. ( 6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Upsher-Smith Laboratories, LLC at 1-855-899-9180 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Strong cytochrome P450 (CYP) 3A inhibitors may increase exposure to doxazosin and increased risk of hypotension. ( 7.1)
• Concomitant administration of doxazosin tablets with a phosphodiesterase-5 (PDE-5) inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension. ( 7.2)

Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in some patients on or previously treated with alpha ₁blockers. This variant of small pupil syndrome is characterized by the combination of a flaccid iris that billows in response to intraoperative irrigation currents, progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs, and potential prolapse of the iris toward the phacoemulsification incisions. The patient's surgeon should be prepared for possible modifications to their surgical technique, such as the utilization of iris hooks, iris dilator rings, or viscoelastic substances. There does not appear to be a benefit of stopping alpha ₁blocker therapy prior to cataract surgery.

In vitrostudies suggest that doxazosin is a substrate of CYP3A4. Strong CYP3A inhibitors may increase exposure to doxazosin. Monitor blood pressure and for symptoms of hypotension when doxazosin tablets are used concomitantly with strong CYP3A inhibitors [see Clinical Pharmacology (12.3)] .

Following the initial dose and with each dose increase of doxazosin tablets, monitor blood pressure for at least 6 hours following administration. If doxazosin tablets administration is discontinued for several days, therapy should be restarted using the initial dosing regimen.

Doxazosin is extensively metabolized in the liver. Hepatic impairment is expected to increase exposure to doxazosin. Use of doxazosin tablets in patients with severe hepatic impairment (Child-Pugh Class C) is not recommended. Monitor blood pressure and for symptoms of hypotension in patients with lesser degrees of hepatic impairment (Child-Pugh Class A and B) [see Clinical Pharmacology (12.3)] .

Doxazosin tablets are an alpha ₁adrenergic antagonist indicated for: ( 1)

• Signs and symptoms of Benign Prostatic Hyperplasia (BPH)
• Treatment of Hypertension

Postural hypotension with or without symptoms (e.g., dizziness) may develop within a few hours following administration of doxazosin tablets. However, infrequently, symptomatic postural hypotension has also been reported later than a few hours after dosing. As with other alpha-blockers, there is a potential for syncope, especially after the initial dose or after an increase in dosage strength. Advise patient how to avoid symptoms resulting from postural hypotension and what measures to take should they develop.

Concomitant administration of doxazosin tablets with a PDE-5 inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension.

• Postural hypotension with or without syncope may occur. ( 5.1)
• Risk of Intraoperative Floppy Iris Syndrome during cataract surgery. ( 5.2)
• Screen for the presence of prostate cancer prior to treatment for BPH and at regular intervals afterwards. ( 5.3)

• For the treatment of BPH: Initiate therapy at 1 mg once daily. Dose may be titrated at 1 to 2 week intervals, up to 8 mg once daily. ( 2.2)
• For the treatment of hypertension: Initiate therapy at 1 mg once daily. Dose may be titrated as needed, up to 16 mg once daily. ( 2.3)

Doxazosin Tablets, USP are available containing 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.
• 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.
• 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.
• 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.

The following adverse reactions have been identified during post-approval use of doxazosin tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

In postmarketing experience, the following additional adverse reactions have been reported:

Blood and Lymphatic System Disorders: leukopenia, thrombocytopenia;

Immune System Disorders: allergic reaction;

Nervous System Disorders: hypoesthesia;

Eye Disorders: Intraoperative Floppy Iris Syndrome [see Warnings and Precautions (5.2)] ;

Cardiac Disorders: bradycardia;

Respiratory, Thoracic and Mediastinal Disorders: bronchospasm aggravated;

Gastrointestinal Disorders: vomiting;

Hepatobiliary Disorders: cholestasis, hepatitis cholestatic;

Skin and Subcutaneous Tissue Disorders: urticaria;

Musculoskeletal and Connective Tissue Disorders: muscle cramps, muscle weakness;

Renal and Urinary Disorders: hematuria, micturition disorder, micturition frequency, nocturia;

Reproductive System and Breast Disorders: gynecomastia, priapism.

• Hepatic Impairment: Monitor for hypotension. ( 8.6, 12.3)

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The recommended initial dosage of doxazosin tablets is 1 mg given once daily either in the morning or evening.

Depending on the individual patient's urodynamics and BPH symptomatology, the dose may be titrated at 1 to 2 week intervals to 2 mg, and thereafter to 4 mg and 8 mg once daily. The maximum recommended dose for BPH is 8 mg once daily.

Routinely monitor blood pressure in these patients.

Advise the patient to read the FDA-approved patient labeling (Patient Information).

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

Doxazosin tablets are indicated for the treatment of the signs and symptoms of BPH.

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 C _maxexposure 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 (C _max) 14 times the C _maxexposure in humans receiving a 12 mg/day therapeutic dose or in Wistar rats at C _maxexposures 15 times human C _maxexposure. There is no evidence that similar lesions occur in humans.

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.

Concomitant administration of doxazosin tablets with a phosphodiesterase-5 (PDE-5) inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension. Monitor blood pressure and for symptoms of hypotension [see Warnings and Precautions (5.1)] .

NDC 0832-0356-11

Doxazosin

Tablets, USP

1 mg

100 Tablets

Rx only

UPSHER-SMITH

NDC 0832-0357-11

Doxazosin

Tablets, USP

2 mg

100 Tablets

Rx only

UPSHER-SMITH

NDC 0832-1358-11

Doxazosin

Tablets, USP

4 mg

100 Tablets

Rx only

UPSHER-SMITH

NDC 0832-1359-11

Doxazosin

Tablets, USP

8 mg

100 Tablets

Rx only

UPSHER-SMITH

Benign Prostatic Hyperplasia (BPH)

The incidence of adverse events has been ascertained from worldwide clinical trials in 965 BPH patients. The incidence rates presented below (Table 2) are based on combined data from seven placebo-controlled trials involving once-daily administration of doxazosin tablets in doses of 1 mg to 16 mg in hypertensives and 0.5 mg to 8 mg in normotensives. Adverse reactions occurring more than 1% more frequently in BPH patients treated with doxazosin tablets versus placebo are summarized in Table 1.

Other adverse reactions occurring less than 1% more frequently in BPH patients treated with doxazosin tablets versus placebo but plausibly related to doxazosin tablets include: palpitations.

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].

Alpha ₁antagonists, including doxazosin, have been associated with priapism (painful penile erection, sustained for hours and unrelieved by sexual intercourse or masturbation). This condition can lead to permanent impotence if not promptly treated.

Experience with doxazosin tablets overdosage is limited. Two adolescents, who each intentionally ingested 40 mg doxazosin tablets with diclofenac or acetaminophen, were treated with gastric lavage with activated charcoal and made full recoveries. A two-year-old child who accidently ingested 4 mg doxazosin tablets was treated with gastric lavage and remained normotensive during the five-hour emergency room observation period. A six-month-old child accidentally received a crushed 1 mg tablet of doxazosin tablets and was reported to have been drowsy. A 32-year-old female with chronic renal failure, epilepsy, and depression intentionally ingested 60 mg doxazosin tablets (blood level = 0.9 mcg/mL; normal values in hypertensives = 0.02 mcg/mL); death was attributed to a grand mal seizure resulting from hypotension. A 39-year-old female who ingested 70 mg doxazosin tablets, alcohol, and Dalmane ^®(flurazepam) developed hypotension which responded to fluid therapy.

The oral LD ₅₀of doxazosin is greater than 1000 mg/kg in mice and rats. The most likely manifestation of overdosage would be hypotension, for which the usual treatment would be intravenous infusion of fluid. As doxazosin is highly protein bound, dialysis would not be indicated.

Doxazosin is a quinazoline compound that is a selective inhibitor of the alpha ₁subtype 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 molecular formula for doxazosin mesylate is C ₂₃H ₂₅N ₅O ₅∙ CH ₄O ₃S and the molecular weight is 547.6. It has the following structure:

Doxazosin 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. Doxazosin tablets, USP are available as tablets for oral use and contains 1 mg, 2 mg, 4 mg and 8 mg of doxazosin as the free base.

The inactive ingredients for all tablets are: microcrystalline cellulose, anhydrous lactose, sodium starch glycolate, magnesium stearate and sodium lauryl sulfate.

Doxazosin tablets are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including this drug.

Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program's Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).

Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.

Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.

Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.

Doxazosin tablets may be used alone or in combination with other antihypertensives.

The initial dosage of doxazosin tablets is 1 mg given once daily. Daily dosage may be doubled up 16 mg once daily, as needed, to achieve the desired reduction in blood pressure.

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.

The safety and effectiveness of doxazosin have not been established in children.

The use of doxazosin tablets is contraindicated in patients with a hypersensitivity to doxazosin, other quinazolines (e.g., prazosin, terazosin), or any of its components.

Carcinoma of the prostate causes many of the symptoms associated with BPH and the two disorders frequently co-exist. Carcinoma of the prostate should therefore be ruled out prior to commencing therapy with doxazosin tablets for the treatment of BPH.

The most commonly reported adverse reactions from clinical trials are fatigue, malaise, hypotension, and dizziness. ( 6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Upsher-Smith Laboratories, LLC at 1-855-899-9180 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Strong cytochrome P450 (CYP) 3A inhibitors may increase exposure to doxazosin and increased risk of hypotension. ( 7.1)
• Concomitant administration of doxazosin tablets with a phosphodiesterase-5 (PDE-5) inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension. ( 7.2)

Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in some patients on or previously treated with alpha ₁blockers. This variant of small pupil syndrome is characterized by the combination of a flaccid iris that billows in response to intraoperative irrigation currents, progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs, and potential prolapse of the iris toward the phacoemulsification incisions. The patient's surgeon should be prepared for possible modifications to their surgical technique, such as the utilization of iris hooks, iris dilator rings, or viscoelastic substances. There does not appear to be a benefit of stopping alpha ₁blocker therapy prior to cataract surgery.

In vitrostudies suggest that doxazosin is a substrate of CYP3A4. Strong CYP3A inhibitors may increase exposure to doxazosin. Monitor blood pressure and for symptoms of hypotension when doxazosin tablets are used concomitantly with strong CYP3A inhibitors [see Clinical Pharmacology (12.3)] .

Following the initial dose and with each dose increase of doxazosin tablets, monitor blood pressure for at least 6 hours following administration. If doxazosin tablets administration is discontinued for several days, therapy should be restarted using the initial dosing regimen.

Doxazosin is extensively metabolized in the liver. Hepatic impairment is expected to increase exposure to doxazosin. Use of doxazosin tablets in patients with severe hepatic impairment (Child-Pugh Class C) is not recommended. Monitor blood pressure and for symptoms of hypotension in patients with lesser degrees of hepatic impairment (Child-Pugh Class A and B) [see Clinical Pharmacology (12.3)] .

Doxazosin tablets are an alpha ₁adrenergic antagonist indicated for: ( 1)

• Signs and symptoms of Benign Prostatic Hyperplasia (BPH)
• Treatment of Hypertension

Postural hypotension with or without symptoms (e.g., dizziness) may develop within a few hours following administration of doxazosin tablets. However, infrequently, symptomatic postural hypotension has also been reported later than a few hours after dosing. As with other alpha-blockers, there is a potential for syncope, especially after the initial dose or after an increase in dosage strength. Advise patient how to avoid symptoms resulting from postural hypotension and what measures to take should they develop.

Concomitant administration of doxazosin tablets with a PDE-5 inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension.

• Postural hypotension with or without syncope may occur. ( 5.1)
• Risk of Intraoperative Floppy Iris Syndrome during cataract surgery. ( 5.2)
• Screen for the presence of prostate cancer prior to treatment for BPH and at regular intervals afterwards. ( 5.3)

• For the treatment of BPH: Initiate therapy at 1 mg once daily. Dose may be titrated at 1 to 2 week intervals, up to 8 mg once daily. ( 2.2)
• For the treatment of hypertension: Initiate therapy at 1 mg once daily. Dose may be titrated as needed, up to 16 mg once daily. ( 2.3)

Doxazosin Tablets, USP are available containing 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.
• 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.
• 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.
• 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.

The following adverse reactions have been identified during post-approval use of doxazosin tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

In postmarketing experience, the following additional adverse reactions have been reported:

Blood and Lymphatic System Disorders: leukopenia, thrombocytopenia;

Immune System Disorders: allergic reaction;

Nervous System Disorders: hypoesthesia;

Eye Disorders: Intraoperative Floppy Iris Syndrome [see Warnings and Precautions (5.2)] ;

Cardiac Disorders: bradycardia;

Respiratory, Thoracic and Mediastinal Disorders: bronchospasm aggravated;

Gastrointestinal Disorders: vomiting;

Hepatobiliary Disorders: cholestasis, hepatitis cholestatic;

Skin and Subcutaneous Tissue Disorders: urticaria;

Musculoskeletal and Connective Tissue Disorders: muscle cramps, muscle weakness;

Renal and Urinary Disorders: hematuria, micturition disorder, micturition frequency, nocturia;

Reproductive System and Breast Disorders: gynecomastia, priapism.

• Hepatic Impairment: Monitor for hypotension. ( 8.6, 12.3)

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The recommended initial dosage of doxazosin tablets is 1 mg given once daily either in the morning or evening.

Depending on the individual patient's urodynamics and BPH symptomatology, the dose may be titrated at 1 to 2 week intervals to 2 mg, and thereafter to 4 mg and 8 mg once daily. The maximum recommended dose for BPH is 8 mg once daily.

Routinely monitor blood pressure in these patients.

Advise the patient to read the FDA-approved patient labeling (Patient Information).

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

Doxazosin tablets are indicated for the treatment of the signs and symptoms of BPH.

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 C _maxexposure 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 (C _max) 14 times the C _maxexposure in humans receiving a 12 mg/day therapeutic dose or in Wistar rats at C _maxexposures 15 times human C _maxexposure. There is no evidence that similar lesions occur in humans.

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.

Concomitant administration of doxazosin tablets with a phosphodiesterase-5 (PDE-5) inhibitor can result in additive blood pressure lowering effects and symptomatic hypotension. Monitor blood pressure and for symptoms of hypotension [see Warnings and Precautions (5.1)] .

NDC 0832-0356-11

Doxazosin

Tablets, USP

1 mg

100 Tablets

Rx only

UPSHER-SMITH

NDC 0832-0357-11

Doxazosin

Tablets, USP

2 mg

100 Tablets

Rx only

UPSHER-SMITH

NDC 0832-1358-11

Doxazosin

Tablets, USP

4 mg

100 Tablets

Rx only

UPSHER-SMITH

NDC 0832-1359-11

Doxazosin

Tablets, USP

8 mg

100 Tablets

Rx only

UPSHER-SMITH