Doxazosin
Generic: DOXAZOSIN
Basic Information
Manufacturer
NuCare Pharmaceuticals, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
40e47e75-6a47-323b-e054-00144ff8d46c
Indications & Usage
INDICATIONS AND USAGE A.
Benign Prostatic Hyperplasia (BPH) Doxazosin tablets USP are indicated for the treatment of both the urinary outflow obstruction and obstructive and irritative symptoms associated with BPH: obstructive symptoms (hesitation, intermittency, dribbling, weak urinary stream, incomplete emptying of the bladder) and irritative symptoms (nocturia, daytime frequency, urgency, burning).
Doxazosin tablets USP may be used in all BPH patients whether hypertensive or normotensive.
In patients with hypertension and BPH, both conditions were effectively treated with doxazosin tablets USP monotherapy.
Doxazosin tablets USP provide rapid improvement in symptoms and urinary flow rate in 66 to 71% of patients.
Sustained improvements with doxazosin tablets USP were seen in patients treated for up to 14 weeks in double-blind studies and up to 2 years in open-label studies.
B.
Hypertension Doxazosin tablets USP 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 USP may be used alone or in combination with diuretics, beta-adrenergic blocking agents, calcium channel blockers, or angiotensin-converting enzyme inhibitors.
Benign Prostatic Hyperplasia (BPH) Doxazosin tablets USP are indicated for the treatment of both the urinary outflow obstruction and obstructive and irritative symptoms associated with BPH: obstructive symptoms (hesitation, intermittency, dribbling, weak urinary stream, incomplete emptying of the bladder) and irritative symptoms (nocturia, daytime frequency, urgency, burning).
Doxazosin tablets USP may be used in all BPH patients whether hypertensive or normotensive.
In patients with hypertension and BPH, both conditions were effectively treated with doxazosin tablets USP monotherapy.
Doxazosin tablets USP provide rapid improvement in symptoms and urinary flow rate in 66 to 71% of patients.
Sustained improvements with doxazosin tablets USP were seen in patients treated for up to 14 weeks in double-blind studies and up to 2 years in open-label studies.
B.
Hypertension Doxazosin tablets USP 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 USP may be used alone or in combination with diuretics, beta-adrenergic blocking agents, calcium channel blockers, or angiotensin-converting enzyme inhibitors.
Warnings
WARNINGS Syncope and "First-dose" Effect Doxazosin, like other alpha-adrenergic blocking agents, can cause marked hypotension, especially in the upright position, with syncope and other postural symptoms such as dizziness.
Marked orthostatic effects are most common with the first dose but can also occur when there is a dosage increase, or if therapy is interrupted for more than a few days.
To decrease the likelihood of excessive hypotension and syncope, it is essential that treatment be initiated with the 1 mg dose.
The 2, 4, and 8 mg tablets are not for initial therapy.
Dosage should then be adjusted slowly (see DOSAGE AND ADMINISTRATION ), with evaluations and increases in dose every two weeks to the recommended dose.
Additional antihypertensive agents should be added with caution.
Patients being titrated with doxazosin should be cautioned to avoid situations where injury could result should syncope occur, during both the day and night.
In an early investigational study of the safety and tolerance of increasing daily doses of doxazosin in normotensives beginning at 1 mg/day, only 2 of 6 subjects could tolerate more than 2 mg/day without experiencing symptomatic postural hypotension.
In another study of 24 healthy normotensive male subjects receiving initial doses of 2 mg/day of doxazosin, seven (29%) of the subjects experienced symptomatic postural hypotension between 0.5 and 6 hours after the first dose, necessitating termination of the study.
In this study, 2 of the normotensive subjects experienced syncope.
Subsequent trials in hypertensive patients always began doxazosin dosing at 1 mg/day, resulting in a 4% incidence of postural side effects at 1 mg/day with no cases of syncope.
In multiple-dose clinical trials in hypertension involving over 1500 hypertensive patients with dose titration every one to two weeks, syncope was reported in 0.7% of patients.
None of these events occurred at the starting dose of 1 mg, and 1.2% (8/664) occurred at 16 mg/day.
In placebo-controlled clinical trials in BPH, 3 out of 665 patients (0.5%) taking doxazosin reported syncope.
Two of the patients were taking 1 mg doxazosin, while one patient was taking 2 mg doxazosin when syncope occurred.
In the open-label, long-term extension follow-up of approximately 450 BPH patients, there were 3 reports of syncope (0.7%).
One patient was taking 2 mg, one patient was taking 8 mg, and one patient was taking 12 mg when syncope occurred.
In a clinical pharmacology study, one subject receiving 2 mg experienced syncope.
If syncope occurs, the patient should be placed in a recumbent position and treated supportively as necessary.
Priapism Rarely (probably less frequently than once in every several thousand patients), alpha 1 antagonists, including doxazosin, have been associated with priapism (painful penile erection, sustained for hours and unrelieved by sexual intercourse or masturbation).
Because this condition can lead to permanent impotence if not promptly treated, patients must be advised about the seriousness of the condition (see PRECAUTIONS, Information for Patients ).
Marked orthostatic effects are most common with the first dose but can also occur when there is a dosage increase, or if therapy is interrupted for more than a few days.
To decrease the likelihood of excessive hypotension and syncope, it is essential that treatment be initiated with the 1 mg dose.
The 2, 4, and 8 mg tablets are not for initial therapy.
Dosage should then be adjusted slowly (see DOSAGE AND ADMINISTRATION ), with evaluations and increases in dose every two weeks to the recommended dose.
Additional antihypertensive agents should be added with caution.
Patients being titrated with doxazosin should be cautioned to avoid situations where injury could result should syncope occur, during both the day and night.
In an early investigational study of the safety and tolerance of increasing daily doses of doxazosin in normotensives beginning at 1 mg/day, only 2 of 6 subjects could tolerate more than 2 mg/day without experiencing symptomatic postural hypotension.
In another study of 24 healthy normotensive male subjects receiving initial doses of 2 mg/day of doxazosin, seven (29%) of the subjects experienced symptomatic postural hypotension between 0.5 and 6 hours after the first dose, necessitating termination of the study.
In this study, 2 of the normotensive subjects experienced syncope.
Subsequent trials in hypertensive patients always began doxazosin dosing at 1 mg/day, resulting in a 4% incidence of postural side effects at 1 mg/day with no cases of syncope.
In multiple-dose clinical trials in hypertension involving over 1500 hypertensive patients with dose titration every one to two weeks, syncope was reported in 0.7% of patients.
None of these events occurred at the starting dose of 1 mg, and 1.2% (8/664) occurred at 16 mg/day.
In placebo-controlled clinical trials in BPH, 3 out of 665 patients (0.5%) taking doxazosin reported syncope.
Two of the patients were taking 1 mg doxazosin, while one patient was taking 2 mg doxazosin when syncope occurred.
In the open-label, long-term extension follow-up of approximately 450 BPH patients, there were 3 reports of syncope (0.7%).
One patient was taking 2 mg, one patient was taking 8 mg, and one patient was taking 12 mg when syncope occurred.
In a clinical pharmacology study, one subject receiving 2 mg experienced syncope.
If syncope occurs, the patient should be placed in a recumbent position and treated supportively as necessary.
Priapism Rarely (probably less frequently than once in every several thousand patients), alpha 1 antagonists, including doxazosin, have been associated with priapism (painful penile erection, sustained for hours and unrelieved by sexual intercourse or masturbation).
Because this condition can lead to permanent impotence if not promptly treated, patients must be advised about the seriousness of the condition (see PRECAUTIONS, Information for Patients ).
Adverse Reactions
ADVERSE REACTIONS A.
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 3) are based on combined data from seven placebo-controlled trials involving once-daily administration of doxazosin in doses of 1 to 16 mg in hypertensives and 0.5 to 8 mg in normotensives.
The adverse events when the incidence in the doxazosin group was at least 1% are summarized in Table 3.
No significant difference in the incidence of adverse events compared to placebo was seen except for dizziness, fatigue, hypotension, edema, and dyspnea.
Dizziness and dyspnea appeared to be dose-related.
TABLE 3 ADVERSE REACTIONS DURING PLACEBO-CONTROLLED STUDIES BENIGN PROSTATIC HYPERPLASIA DOXAZOSIN PLACEBO Body System (N=665) (N=300) BODY AS A WHOLE Back Pain 1.8% 2.0% Chest Pain 1.2% 0.7% Fatigue 8.0% p ≤0.05 for treatment differences 1.7% Headache 9.9% 9.0% Influenza-like Symptoms 1.1% 1.0% Pain 2.0% 1.0% CARDIOVASCULAR SYSTEM Hypotension 1.7% 0.0% Palpitation 1.2% 0.3% DIGESTIVE SYSTEM Abdominal Pain 2.4% 2.0% Diarrhea 2.3% 2.0% Dyspepsia 1.7% 1.7% Nausea 1.5% 0.7% METABOLIC AND NUTRITIONAL DISORDERS Edema 2.7% 0.7% NERVOUS SYSTEM Dizziness Includes vertigo 15.6% 9.0% Mouth Dry 1.4% 0.3% Somnolence 3.0% 1.0% RESPIRATORY SYSTEM Dyspnea 2.6% 0.3% Respiratory Disorder 1.1% 0.7% SPECIAL SENSES Vision Abnormal 1.4% 0.7% UROGENITAL SYSTEM Impotence 1.1% 1.0% Urinary Tract Infection 1.4% 2.3% SKIN & APPENDAGES Sweating Increased 1.1% 1.0% PSYCHIATRIC DISORDERS Anxiety 1.1% 0.3% Insomnia 1.2% 0.3% In these placebo-controlled studies of 665 doxazosin patients treated for a mean of 85 days, additional adverse reactions have been reported.
These are less than 1% and not distinguishable from those that occurred in the placebo group.
Adverse reactions with an incidence of less than 1% but of clinical interest are (doxazosin vs.
placebo): Cardiovascular System: angina pectoris (0.6% vs.
0.7%), postural hypotension (0.3% vs.
0.3%), syncope (0.5% vs.
0.0%), tachycardia (0.9% vs.
0.0%); Urogenital System: dysuria (0.5% vs.
1.3%); and Psychiatric Disorders: libido decreased (0.8% vs.
0.3%).
The safety profile in patients treated for up to three years was similar to that in the placebo-controlled studies.
The majority of adverse experiences with doxazosin were mild.
B.
Hypertension Doxazosin has been administered to approximately 4000 hypertensive patients, of whom 1679 were included in the hypertension clinical development program.
In that program, minor adverse effects were frequent, but led to discontinuation of treatment in only 7% of patients.
In placebo-controlled studies, adverse effects occurred in 49% and 40% of patients in the doxazosin and placebo groups, respectively, and led to discontinuation in 2% of patients in each group.
The major reasons for discontinuation were postural effects (2%), edema, malaise/fatigue, and some heart rate disturbance, each about 0.7%.
In controlled hypertension clinical trials directly comparing doxazosin to placebo, there was no significant difference in the incidence of side effects, except for dizziness (including postural), weight gain, somnolence, and fatigue/malaise.
Postural effects and edema appeared to be dose-related.
The prevalence rates presented below are based on combined data from placebo-controlled studies involving once-daily administration of doxazosin at doses ranging from 1 to 16 mg.
Table 4 summarizes those adverse experiences (possibly/probably related) reported for patients in these hypertension studies where the prevalence rate in the doxazosin group was at least 0.5% or where the reaction is of particular interest.
TABLE 4 ADVERSE REACTIONS DURING PLACEBO-CONTROLLED STUDIES HYPERTENSION DOXAZOSIN PLACEBO (N=339) (N=336) CARDIOVASCULAR SYSTEM Dizziness 19% 9% Vertigo 2% 1% Postural Hypotension 0.3% 0% Edema 4% 3% Palpitation 2% 3% Arrhythmia 1% 0% Hypotension 1% 0% Tachycardia 0.3% 1% Peripheral Ischemia 0.3% 0% SKIN & APPENDAGES Rash 1% 1% Pruritus 1% 1% MUSCULOSKELETAL SYSTEM Arthralgia/Arthritis 1% 0% Muscle Weakness 1% 0% Myalgia 1% 0% CENTRAL & PERIPHERAL N.S.
Headache 14% 16% Paresthesia 1% 1% Kinetic Disorders 1% 0% Ataxia 1% 0% Hypertonia 1% 0% Muscle Cramps 1% 0% AUTONOMIC Mouth Dry 2% 2% Flushing 1% 0% SPECIAL SENSES Vision Abnormal 2% 1% Conjunctivitis/Eye Pain 1% 1% Tinnitus 1% 0.3% PSYCHIATRIC Somnolence 5% 1% Nervousness 2% 2% Depression 1% 1% Insomnia 1% 1% Sexual Dysfunction 2% 1% GASTROINTESTINAL Nausea 3% 4% Diarrhea 2% 3% Constipation 1% 1% Dyspepsia 1% 1% Flatulence 1% 1% Abdominal Pain 0% 2% Vomiting 0% 1% RESPIRATORY Rhinitis 3% 1% Dyspnea 1% 1% Epistaxis 1% 0% URINARY Polyuria 2% 0% Urinary Incontinence 1% 0% Micturition Frequency 0% 2% GENERAL Fatigue/Malaise 12% 6% Chest Pain 2% 2% Asthenia 1% 1% Face Edema 1% 0% Pain 2% 2% Additional adverse reactions have been reported, but these are, in general, not distinguishable from symptoms that might have occurred in the absence of exposure to doxazosin.
The following adverse reactions occurred with a frequency of between 0.5% and 1%: syncope, hypoesthesia, increased sweating, agitation, increased weight.
The following additional adverse reactions were reported by <0.5% of 3960 patients who received doxazosin in controlled or open, short- or long-term clinical studies, including international studies.
Cardiovascular System: angina pectoris, myocardial infarction, cerebrovascular accident; Autonomic Nervous System: pallor; Metabolic: thirst, gout, hypokalemia; Hematopoietic: lymphadenopathy, purpura; Reproductive System: breast pain; Skin Disorders: alopecia, dry skin, eczema; Central Nervous System: paresis, tremor, twitching, confusion, migraine, impaired concentration; Psychiatric: paroniria, amnesia, emotional lability, abnormal thinking, depersonalization; Special Senses: parosmia, earache, taste perversion, photophobia, abnormal lacrimation; Gastrointestinal System: increased appetite, anorexia, fecal incontinence, gastroenteritis; Respiratory System: bronchospasm, sinusitis, coughing, pharyngitis; Urinary System: renal calculus; General Body System: hot flushes, back pain, infection, fever/rigors, decreased weight, influenza-like symptoms.
Doxazosin has not been associated with any clinically significant changes in routine biochemical tests.
No clinically relevant adverse effects were noted on serum potassium, serum glucose, uric acid, blood urea nitrogen, creatinine or liver function tests.
Doxazosin has been associated with decreases in white blood cell counts (see PRECAUTIONS, Leukopenia/Neutropenia ).
In post-marketing experience, the following additional adverse reactions have been reported: Autonomic Nervous System: priapism; Central Nervous System: hypoesthesia; Endocrine System: gynecomastia; Gastrointestinal System: vomiting; General Body System: allergic reaction; Heart Rate/Rhythm: bradycardia; Hematopoietic: leukopenia, thrombocytopenia; Liver/Biliary System: hepatitis, hepatitis cholestatic; Respiratory System: bronchospasm aggravated; Skin Disorders: urticaria; Special Senses: Intraoperative Floppy Iris Syndrome (see PRECAUTIONS, Cataract Surgery ); Urinary System: hematuria, micturition disorder, micturition frequency, nocturia.
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 3) are based on combined data from seven placebo-controlled trials involving once-daily administration of doxazosin in doses of 1 to 16 mg in hypertensives and 0.5 to 8 mg in normotensives.
The adverse events when the incidence in the doxazosin group was at least 1% are summarized in Table 3.
No significant difference in the incidence of adverse events compared to placebo was seen except for dizziness, fatigue, hypotension, edema, and dyspnea.
Dizziness and dyspnea appeared to be dose-related.
TABLE 3 ADVERSE REACTIONS DURING PLACEBO-CONTROLLED STUDIES BENIGN PROSTATIC HYPERPLASIA DOXAZOSIN PLACEBO Body System (N=665) (N=300) BODY AS A WHOLE Back Pain 1.8% 2.0% Chest Pain 1.2% 0.7% Fatigue 8.0% p ≤0.05 for treatment differences 1.7% Headache 9.9% 9.0% Influenza-like Symptoms 1.1% 1.0% Pain 2.0% 1.0% CARDIOVASCULAR SYSTEM Hypotension 1.7% 0.0% Palpitation 1.2% 0.3% DIGESTIVE SYSTEM Abdominal Pain 2.4% 2.0% Diarrhea 2.3% 2.0% Dyspepsia 1.7% 1.7% Nausea 1.5% 0.7% METABOLIC AND NUTRITIONAL DISORDERS Edema 2.7% 0.7% NERVOUS SYSTEM Dizziness Includes vertigo 15.6% 9.0% Mouth Dry 1.4% 0.3% Somnolence 3.0% 1.0% RESPIRATORY SYSTEM Dyspnea 2.6% 0.3% Respiratory Disorder 1.1% 0.7% SPECIAL SENSES Vision Abnormal 1.4% 0.7% UROGENITAL SYSTEM Impotence 1.1% 1.0% Urinary Tract Infection 1.4% 2.3% SKIN & APPENDAGES Sweating Increased 1.1% 1.0% PSYCHIATRIC DISORDERS Anxiety 1.1% 0.3% Insomnia 1.2% 0.3% In these placebo-controlled studies of 665 doxazosin patients treated for a mean of 85 days, additional adverse reactions have been reported.
These are less than 1% and not distinguishable from those that occurred in the placebo group.
Adverse reactions with an incidence of less than 1% but of clinical interest are (doxazosin vs.
placebo): Cardiovascular System: angina pectoris (0.6% vs.
0.7%), postural hypotension (0.3% vs.
0.3%), syncope (0.5% vs.
0.0%), tachycardia (0.9% vs.
0.0%); Urogenital System: dysuria (0.5% vs.
1.3%); and Psychiatric Disorders: libido decreased (0.8% vs.
0.3%).
The safety profile in patients treated for up to three years was similar to that in the placebo-controlled studies.
The majority of adverse experiences with doxazosin were mild.
B.
Hypertension Doxazosin has been administered to approximately 4000 hypertensive patients, of whom 1679 were included in the hypertension clinical development program.
In that program, minor adverse effects were frequent, but led to discontinuation of treatment in only 7% of patients.
In placebo-controlled studies, adverse effects occurred in 49% and 40% of patients in the doxazosin and placebo groups, respectively, and led to discontinuation in 2% of patients in each group.
The major reasons for discontinuation were postural effects (2%), edema, malaise/fatigue, and some heart rate disturbance, each about 0.7%.
In controlled hypertension clinical trials directly comparing doxazosin to placebo, there was no significant difference in the incidence of side effects, except for dizziness (including postural), weight gain, somnolence, and fatigue/malaise.
Postural effects and edema appeared to be dose-related.
The prevalence rates presented below are based on combined data from placebo-controlled studies involving once-daily administration of doxazosin at doses ranging from 1 to 16 mg.
Table 4 summarizes those adverse experiences (possibly/probably related) reported for patients in these hypertension studies where the prevalence rate in the doxazosin group was at least 0.5% or where the reaction is of particular interest.
TABLE 4 ADVERSE REACTIONS DURING PLACEBO-CONTROLLED STUDIES HYPERTENSION DOXAZOSIN PLACEBO (N=339) (N=336) CARDIOVASCULAR SYSTEM Dizziness 19% 9% Vertigo 2% 1% Postural Hypotension 0.3% 0% Edema 4% 3% Palpitation 2% 3% Arrhythmia 1% 0% Hypotension 1% 0% Tachycardia 0.3% 1% Peripheral Ischemia 0.3% 0% SKIN & APPENDAGES Rash 1% 1% Pruritus 1% 1% MUSCULOSKELETAL SYSTEM Arthralgia/Arthritis 1% 0% Muscle Weakness 1% 0% Myalgia 1% 0% CENTRAL & PERIPHERAL N.S.
Headache 14% 16% Paresthesia 1% 1% Kinetic Disorders 1% 0% Ataxia 1% 0% Hypertonia 1% 0% Muscle Cramps 1% 0% AUTONOMIC Mouth Dry 2% 2% Flushing 1% 0% SPECIAL SENSES Vision Abnormal 2% 1% Conjunctivitis/Eye Pain 1% 1% Tinnitus 1% 0.3% PSYCHIATRIC Somnolence 5% 1% Nervousness 2% 2% Depression 1% 1% Insomnia 1% 1% Sexual Dysfunction 2% 1% GASTROINTESTINAL Nausea 3% 4% Diarrhea 2% 3% Constipation 1% 1% Dyspepsia 1% 1% Flatulence 1% 1% Abdominal Pain 0% 2% Vomiting 0% 1% RESPIRATORY Rhinitis 3% 1% Dyspnea 1% 1% Epistaxis 1% 0% URINARY Polyuria 2% 0% Urinary Incontinence 1% 0% Micturition Frequency 0% 2% GENERAL Fatigue/Malaise 12% 6% Chest Pain 2% 2% Asthenia 1% 1% Face Edema 1% 0% Pain 2% 2% Additional adverse reactions have been reported, but these are, in general, not distinguishable from symptoms that might have occurred in the absence of exposure to doxazosin.
The following adverse reactions occurred with a frequency of between 0.5% and 1%: syncope, hypoesthesia, increased sweating, agitation, increased weight.
The following additional adverse reactions were reported by <0.5% of 3960 patients who received doxazosin in controlled or open, short- or long-term clinical studies, including international studies.
Cardiovascular System: angina pectoris, myocardial infarction, cerebrovascular accident; Autonomic Nervous System: pallor; Metabolic: thirst, gout, hypokalemia; Hematopoietic: lymphadenopathy, purpura; Reproductive System: breast pain; Skin Disorders: alopecia, dry skin, eczema; Central Nervous System: paresis, tremor, twitching, confusion, migraine, impaired concentration; Psychiatric: paroniria, amnesia, emotional lability, abnormal thinking, depersonalization; Special Senses: parosmia, earache, taste perversion, photophobia, abnormal lacrimation; Gastrointestinal System: increased appetite, anorexia, fecal incontinence, gastroenteritis; Respiratory System: bronchospasm, sinusitis, coughing, pharyngitis; Urinary System: renal calculus; General Body System: hot flushes, back pain, infection, fever/rigors, decreased weight, influenza-like symptoms.
Doxazosin has not been associated with any clinically significant changes in routine biochemical tests.
No clinically relevant adverse effects were noted on serum potassium, serum glucose, uric acid, blood urea nitrogen, creatinine or liver function tests.
Doxazosin has been associated with decreases in white blood cell counts (see PRECAUTIONS, Leukopenia/Neutropenia ).
In post-marketing experience, the following additional adverse reactions have been reported: Autonomic Nervous System: priapism; Central Nervous System: hypoesthesia; Endocrine System: gynecomastia; Gastrointestinal System: vomiting; General Body System: allergic reaction; Heart Rate/Rhythm: bradycardia; Hematopoietic: leukopenia, thrombocytopenia; Liver/Biliary System: hepatitis, hepatitis cholestatic; Respiratory System: bronchospasm aggravated; Skin Disorders: urticaria; Special Senses: Intraoperative Floppy Iris Syndrome (see PRECAUTIONS, Cataract Surgery ); Urinary System: hematuria, micturition disorder, micturition frequency, nocturia.